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mRNA Vaccines

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Last reviewed: June 15, 2022 

The following is a curated review of key information and literature about this topic. It is not comprehensive of all data related to this subject. 

 

Overview and Mechanism 

mRNA vaccines contain messenger RNA (mRNA), a single-stranded RNA molecule that complements DNA. It is created in the nucleus, when DNA is transcribed by RNA polymerase to create pre-mRNA (Zipursky, 2000). Pre-mRNA is then spliced into mRNA, which is exported from the nucleus to the cytoplasm and “read” by ribosomes (the translation machinery of cells). Ribosomes then make proteins.  

mRNA vaccines use lab-created mRNA encapsulated within nanoparticles. Translation of the mRNA results in the development of a protein antigen that triggers an immune response (Schlake, 2012). mRNA vaccines deliver mRNA directly to the cytoplasm, where it is translated by ribosomes. The mRNA does not enter the nucleus and therefore cannot be incorporated into the genome. Its presence in the cell is transient, and it is quickly metabolized and eliminated via cellular processing mechanisms (Pardi, 2018).  

Unlike conventional vaccines, which can take months to produce, mRNA vaccines can be created quickly and are more easily scaled because they are based on an organism’s genetic code.  

The concept of mRNA vaccines was first developed in the early 1990s (Schlake, 2012). However, due to difficulty with the inherent instability of mRNA, as well as delivery challenges and other factors, the field did not make significant strides until the past decade, when technological advances and investment led to significant development. Prior to the COVID-19 pandemic, mRNA vaccines targeting infectious diseases including HIV-1, rabies, Zika and influenza were already in clinical trials, as were mRNA vaccines targeting multiple hematologic and solid organ malignancies (Pardi, 2018). 

Soon after the COVID-19 pandemic emerged, Pfizer and BioNTech began to develop an mRNA vaccine against SARS-CoV-2, as did Moderna — the latter in partnership with the National Institute of Allergy and Infectious Diseases. 

  • The Pfizer-BioNTech vaccine, BNT162b2, uses mRNA to create the receptor binding domain of the spike protein of SARS-CoV-2 (Walsh, 2020). The spike protein is what SARS-CoV-2 uses to attach to host cells and enter them. 
  • The Moderna vaccine, mRNA-1273, uses mRNA to create the SARS-CoV-2 spike protein stabilized in its prefusion conformation (Jackson, 2020).  

Studies of both vaccines have shown them to be highly effective in preventing symptomatic COVID-19 and safe after several months of follow-up.  

Efficacy 

Both the Pfizer-BioNTech and Moderna COVID-19 vaccines are highly effective against both symptomatic and severe COVID-19 across age groups and in diverse populations (see literature subsections for Pfizer-BioNTech and Moderna). However, effectiveness against different SARS-CoV-2 variants varies and appears to wane over time (see Immunity page). This is likely true both for adult and pediatric populations (see Emerging Variants page).  

Some studies directly comparing the relative effectiveness of these two mRNA vaccines have shown a slightly higher and/or more durable protective effect of the Moderna COVID-19 vaccine compared with the Pfizer-BioNTech COVID-19 vaccine (Collier, November 2021; Tenforde, November 2021; Bajema, December 2021; Dickerman, January 2022; Risk, February 2022). This finding has some biological plausibility given the difference in antibody responses elicited by these vaccines (Steensels, August 2021; Collier, November 2021; Bajema, December 2021). However, conclusions about relative effectiveness are limited by the fact that these vaccines were not distributed evenly over time and distribution varied geographically. Other factors, such as characteristics of the populations receiving each vaccine and local COVID-19 disease epidemiology, likely influenced some of the observed differences in vaccine effectiveness between the Pfizer-BioNTech and Moderna COVID-19 vaccines.

Safety 

In post-authorization observational and surveillance studies, both the Pfizer-BioNTech and Moderna COVID-19 vaccines have been demonstrated to be safe (Gee, February 2021Barda, September 2021Klein, October 2021). The patterns of solicited local and systemic adverse reactions mirror those observed in the Phase 3 clinical trials of both vaccines. 

Two notable but rare adverse events that were only identified in post-authorization studies include acute allergic reactions (Banerji, April 2021) as well as myocarditis/pericarditis following either vaccine. These events have not been identified as safety concerns in ongoing clinical trials in younger populations (6 months–4 years for Pfizer-BioNTech; 6 months–17 years for Moderna), but will continue to be monitored in clinical trials and post-authorization studies.

Acute allergic reactions 

Anaphylaxis and serious allergic reactions were not observed in the clinical trials of mRNA COVID-19 vaccines, but were recognized shortly after they were authorized for use and deployed in mass vaccination campaigns. There have been no US-based reports of anaphylaxis after COVID-19 vaccination in children 6 months–11 years of age.

In two separate analyses of data submitted to the Vaccine Adverse Events Reporting System, which comprised reports from 1,893,360 first doses of the Pfizer-BioNTech COVID-19 vaccine and 4,041,396 first doses of the Moderna COVID-19 vaccine in the U.S., there were just 175 cases of possible allergic reactions after the Pfizer-BioNTech vaccine and just 108 cases of possible allergic reactions after the Moderna vaccine. 

  • Of the 175 reactions reported after the Pfizer-BioNTech vaccine, only 21 (12%) met the Brighton Collaboration case definition criteria for anaphylaxis. Most of these were in women (n=19, 90%) and median time to onset of symptoms was 15 minutes. Four of the cases required hospitalization, while 17 were managed in the emergency department. Most of the cases of anaphylaxis had a documented history of allergies to drugs, foods or insect stings (n=17, 81%), and 7 (33%) had previously experienced anaphylaxis. The 83 non-anaphylaxis reactions were also predominantly in women (90%), with a 12-minute median interval to symptom onset. These reactions included pruritus, rash, itchy and scratchy sensations in the throat and mild respiratory symptoms (CDC COVID-19 Response Team, January 2021). 
  • Of the 108 reactions reported after the Moderna vaccine, only 10 (9%) met the Brighton Collaboration case definition criteria for anaphylaxis. All of these were in women and median time to onset of symptoms was 7.5 minutes. Six of the cases required hospitalization (5 in the ICU, 4 of whom required intubation) and 4 were managed in the emergency department. Most (n=9, 90%) of the cases of anaphylaxis had a documented history of allergies to drugs or foods, and 5 (50%) had previously experienced anaphylaxis. There were 43 non-anaphylaxis reactions that were also predominantly in women (91%) with the median interval to symptom onset being 14 minutes. These reactions included pruritus, rash, itchy sensations in the mouth or throat, sensation of throat closure and respiratory symptoms (CDC COVID-19 Response Team, January 2021). 

Additional data submitted to FDA from ongoing clinical trials in children 6 months–4 years (Pfizer-BioNTech) and individuals 6 months–17 years (Moderna)  also support the conclusion that the safety profile of these vaccines in pediatric populations is robust. 

  • There was one report of anaphylaxis in an ongoing  clinical trial of Moderna  vaccine administered in children aged 6 months–17 years. This report was in a 3-year-old female ("anaphylaxis due  to Miralax”) which was considered related to the study vaccine by the study investigator, but which was later assessed not to be related to vaccine by FDA. The event occurred 32 days after vaccine dose 1, symptoms resolved the same day, and the patient  went on to receive a second dose  of vaccine with no additional adverse events reported. 
  • In an ongoing clinical trial of Pfizer-BioNTech vaccine administered to children aged 6 months–4 years, there were no reports of anaphylaxis that were determined to be related to the vaccine. 

Finally, in a prospective study of 64,900 Mass General Brigham employees who received a first dose of a mRNA COVID-19 vaccine between Dec. 16, 2020 and Feb. 12, 2021, 1,365 (2.1%) of employees reported any allergic symptoms, and there were 16 (0.025%) employees that experienced of anaphylaxis. Rates of allergic reactions were slightly higher with the Moderna COVID-19 vaccine (2.20 vs. 1.95%, p=0.03). Nearly all (n=15, 94%) of the cases of anaphylaxis were among women, and nearly a third (n=5, 31%) had a history of anaphylaxis. One of the cases of anaphylaxis required ICU admission, 9 received IM epinephrine and all recovered without sequelae (Blumenthal, March 2021). CDC has developed recommendations for management of individuals with a history of anaphylaxis or other allergic reactions to the specific ingredients contained within the COVID-19 vaccines or to other substances. 

Myocarditis/pericarditis 

These were two large retrospective population-based cohort studies conducted in Israel to analyze the incidence and risk factors for myocarditis associated with mRNA COVID-19 vaccination (largely the Pfizer-BioNTech COVID-19 vaccine, which was deployed early in Israel) (Witberg, October 2021Mevorach, October 2021). The incidence was highest among young men (aged 16-29) and following the second dose of the vaccine. The majority of cases were mild-moderate in severity. 

In a presentation of VAERS safety data to FDA’s Vaccines and Related Biological Products Advisory Committee in June 2021, a total of 789 cases of myocarditis/pericarditis following mRNA COVID-19 vaccines (488 Pfizer-BioNTech, 301 Moderna) were identified (216 after the first dose, 573 after the second dose). The observed rate of myocarditis/pericarditis was higher than what would be expected based on population-level background incidence rates. The median age at time of onset was 30 years (range 12-94) for cases after dose 1 and 24 years (range 14-87) for cases after dose 2. The majority of cases (75%) occurred in males. 

In ongoing clinical trials assessing the safety and effectiveness of Pfizer-BioNTech vaccine for children 6 months–4 years, no instances of myocarditis after vaccination were reported. In ongoing clinical trials assessing the safety and effectiveness of Moderna vaccine for children 6 months–17 years, there was one report of an adverse event that was clinically concerning for vaccine-associated myocarditis in a 12-year-old male who had received the study vaccine the previous day. The individual was seen in the ER, with normal chest X-ray and sinus tachycardia with non-specific T-wave abnormalities, discharged with ibuprofen and oral dexamethasone, and his symptoms resolved the same day. Review and monitoring of potential myocarditis events after vaccination in these age groups will continue.  

Neurologic events

There was a numerical imbalance in the number of cases of Bell’s palsy identified among recipients of the Pfizer-BioNTech and Moderna COVID-19 vaccines in Phase 3 clinical trials. Four participants who received the Pfizer-BioNTech vaccine later developed Bell’s palsy (compared to zero in the placebo group of that study) and three participants who received the Moderna vaccine later developed Bell’s palsy (compared to one in the placebo group of that study). Overall, this was too few cases of Bell’s palsy to establish a statistically significant association with vaccination (Ozonoff, April 2021), but surveillance is ongoing. 

There have been no cases of transverse myelitis or Guillain-Barré syndrome reported following vaccination among participants in either of the mRNA COVID-19 vaccine clinical trials, including ongoing clinical trials of children aged 6 months–4 years (Pfizer-BioNTech) and children aged 6 months–17 years (Moderna).  

A history of any of these conditions is not a contraindication or precaution to vaccination with either mRNA COVID-19 vaccine. Any occurrence of these conditions following mRNA COVID-19 vaccination should be reported to VAERS. 

 

Immunogenicity 

The Pfizer-BioNTech and Moderna COVID-19 vaccines were demonstrated to elicit robust immune responses against SARS-CoV-2 across patient populations in clinical trials. Post-authorization immunogenicity studies of these vaccines have focused on questions that may be relevant to vaccine implementation, including vaccination of previously infected individuals, comparative immunogenicity between the vaccines and mixed-product schedules. 

  • Antibody Responses in Seropositive Persons after a Single Dose of SARS-CoV-2 mRNA Vaccine (Krammer, April 2021). This analysis of anti-SARS-CoV-2 spike IgG antibody responses to a single dose of an mRNA COVID-19 vaccine included a total of 110 individuals with or without documented preexisting immunity to SARS-CoV-2. Of these, 67 participants were seronegative and 43 were seropositive, with a mean age of 40.0 years (range, 24-68). The majority of participants received the Pfizer-BioNTech COVID-19 vaccine (N=88, 80%), with the remainder (N=22, 20%) receiving the Moderna COVID-19 vaccine. Most seronegative individuals had low antibody titers for up to 12 days post-vaccination, whereas seropositive individuals had significantly higher titers within days (some within 4 days) after vaccination. Post-vaccination antibody titers among those with preexisting immunity were 10-45 times higher than in seronegative individuals at the same time points, even exceeding the antibody titers achieved by this group after the second dose of the vaccine by a factor of six. Seropositive individuals demonstrated no further increase in antibody titers after the second dose of vaccine, compared with seronegative individuals whose titers increased by a factor of three after the second dose. 
  • Comparison of SARS-CoV-2 Antibody Response Following Vaccination with BNT162b2 and mRNA-1273 (Steensels, August 2021). In this prospective cohort study, investigators in Belgium compared anti-spike antibody responses (assessed using a commercial antibody assay) in previously unvaccinated health care workers following a two-dose series of either the Pfizer-BioNTech or Moderna COVID-19 vaccine. The investigators further stratified their analysis based on prior SARS-CoV-2 infection status. Of 1,647 individuals that enrolled in the study, 959 (58%) received the Pfizer-BioNTech COVID-19 vaccine and 688 (42%) received the Moderna COVID-19 vaccine. Individuals who received the Moderna COVID-19 vaccine had higher geometric mean titers of anti-spike antibodies compared with recipients of the Pfizer-BioNTech COVID-19 vaccine, regardless of age group or prior SARS-CoV-2 infection status. 
  • In data from an ongoing clinical trial to assess Pfizer-BioNTech vaccine in children 6 months–4 years, vaccine immunogenicity measured by geometric mean titer (GMT) was comparable to vaccine immunogenicity previously measured by GMT in individuals 16-25 years of age. 
  • In data from an ongoing clinical trial to assess Moderna vaccine in children 6 months–17 years, vaccine immunogenicity measured by geometric mean titer (GMT) or geometric mean concentration (GMC) was comparable to vaccine immunogenicity previously measured in adults 18-25 years of age. 

 

Pfizer-BioNTech COVID-19 Vaccine  

Overview

The vaccine, BNT162b2, was fully approved by FDA in August 2021 for individuals 16 years of age and older. It currently has emergency use authorization for children 6 months–15 years of age.

Literature 

Effectiveness of the BNT162b2 Vaccine Among Children 5-11 and 12-17 Years in New York After the Emergence of the Omicron Variant (Dorabawila, February 2022 preprint, not peer-reviewed). 

This is a preprint (not peer-reviewed) report of vaccine effectiveness against COVID-19 cases and hospitalizations in children and adolescents 5-11 and 12-17, using New York State Department of Health data. This analysis identified declining VE against COVID-19 infection over time. VE against hospitalization also declined over time, most substantially for children 5-11 years, although confidence intervals were very wide. 

Study population: 

  • This analysis linked three New York state databases to identify COVID-19 cases and hospitalizations among children and adolescents 5-17 years old and to identify vaccination status.
  • The analysis compared “fully vaccinated” (two doses received at least 14 days ago) individuals with unvaccinated individuals. The analysis was grouped by age (children 5-11 years and adolescents 12-17 years old).
  • Incidence rate ratios and VE estimates were calculated by dividing the incidence rate in unvaccinated individuals by the incidence rate in vaccinated individuals. VE was calculated as 100 x (1 – (1/IRR)). 

Key findings: 

  • For adolescents 12-17 years, VE against infection declined from 85% (95% CI, 84%-86%) to 51% (95% CI, 48%-54%) from the week of Nov. 29 to Jan. 24, a time period of increasing Omicron predominance. 
  • For children 5-11 years, VE against infection declined from 68% (95% CI, 63%-72%) to 12% (95% CI, 6%-16%) from the week of Dec. 13 to Jan. 24.
  • VE against hospitalization by Jan. 24 was higher than VE against infection for both age groups. For adolescents 12-17 years, VE against hospitalization was 73% (95% CI,53%-87%); for children 5-11 years, VE was 48% (95% CI, -12% to 75%). 

Limitations: 

  • This is not a peer-reviewed research article. Changes to the analytic procedures or case/outcome ascertainment may occur during the peer-review process, which could change the findings. 
  • VE estimation in this study did not include common confounders such as sex or race in multivariable analyses.
  • This study was not able to identify the results of home testing, which may influence VE estimates for infections (but not hospitalizations).
  • There were few hospitalizations in the analysis, making confidence intervals for VE against hospitalization very wide.
  • It is challenging to directly compare VE in 5-11 year olds to VE in 12-17 year olds, due to changes in vaccine eligibility and availability during the time frame of the study. 

Effectiveness of COVID-19 Pfizer-BioNTech BNT162b2 mRNA Vaccination in Preventing COVID-19–Associated Emergency Department and Urgent Care Encounters and Hospitalizations Among Nonimmunocompromised Children and Adolescents Aged 5–17 Years — VISION Network, 10 States, April 2021–January 2022 (Klein, March 2022). 

In this MMWR analysis of children and adolescents 5-17 years of age in the VISION network, two doses of Pfizer-BioNTech mRNA vaccine protected against COVID-19associated emergency department and urgent care visits. However, vaccine effectiveness declined over time and was lower against Omicron illnesses compared to COVID-19 caused by the ancestral strain or by other variants of concern. Booster doses increased vaccine effectiveness during periods of Omicron dominance. 

Study population: 

  • This analysis included eligible medical encounters (emergency department and urgent care visits) in individuals 5-17 years old, who received SARS-CoV-2 molecular testing (primarily by RT-PCR) at seven medical centers that are part of the VISION Network.  
  • VE was estimated using a test-negative design, comparing the odds of a positive SARS-CoV-2 test result among individuals who were vaccinated (i.e., received two doses of mRNA vaccine at least 14 days earlier or three doses at least 7 days earlier) or unvaccinated, in a multivariable logistic regression analysis.  

Key findings: 

  • There were 39,217 eligible encounters, of which 23.4% were among children 5-11 years, 46.2% were among adolescents 12-15 years, and 30.3% were in adolescents 16-17 years.
  • Of 1,699 hospitalizations, 16.8% were in children 5-11 years, 43.6% were among adolescents 12-15 years, and 39.6% were among adolescents 16-17 years.
  • Most encounters and hospitalizations for adolescents 12-15 years and 16-17 years occurred during periods of Delta circulation; most encounters and hospitalizations for children 5-11 years occurred during periods of Omicron. This reflects differences in the timing of age recommendations for vaccines.
  • VE against emergency department or urgent care encounters:
    • VE was 46% (95% CI, 24%-61%) for 5-11 year olds who received two doses 14-67 days prior to illness.
    • For adolescents 12-15 years, VE was 83% (95% CI, 80%-85%) for two doses received 14-149 days earlier but 38% (95% CI, 28%48%) for two doses received ≥150 days earlier.
    • For adolescents 16-17 years, VE was 76% (95% CI, 71%-80%) for two doses received 14-149 days earlier but 46% (95% CI, 36%-54%) for two doses received ≥150 days earlier.
    • VE in adolescents 12-15 years was 45% (95% CI, 30%-57%) during the Omicron period, compared to 92% (95% CI, 89%94%) during the Delta period, for two doses received 14-149 days earlier.
    • VE in adolescents 16-17 years was 34% (95% CI, 8%-53%) during the Omicron period, compared to 85% (95% CI, 81%-89%) during the Delta period, for two doses received 14-149 days earlier.
  • VE against hospitalization:
    • VE was high for all age groups: 74% (95% CI, -35% to 95%) for children 5-11, 92% (95% CI, 79%-97%) for adolescents 12-15 and 94% (95% CI, 87%-97%) for adolescents 16-17, for two doses received 14-149 days earlier.
    • VE against hospitalization for two doses received ≥150 days earlier was slightly lower compared to two doses received 14-149 days earlier for 12-15-year-olds (VE: 73%; 95% CI, 43%-88%) and for 16-17-year-olds (VE: 88%; 95% CI, 72%-95%). 

Limitations: 

  • Due to small numbers of observations, VE was not calculated for 5-11 year olds during pre-Omicron periods. VE was also not calculated for 5-11 year olds for three doses, or for two doses received ≥150 days earlier. 
  • It is difficult to directly compare VE estimates between age groups due to differences in eligibility and availability over time. 
  • Due to low numbers of observations for some outcomes, 95% confidence intervals are wide.
  • There may be remaining uncontrolled confounding due to mask use, physical distancingand other pandemic control measures that may differ between children and adolescents of different ages.
  • Because genetic characterization could not be done, VE is calculated simply during periods of Omicron or Delta predominance; individual illnesses cannot be categorized as “caused by Omicron” or “caused by Delta.”
  • These data come from seven medical centers serving heterogeneous populations and communities, but the data may not be generalizable more broadly to the U.S. population. 

Evaluation of the BNT162b2 COVID-19 Vaccine in Children 5 to 11 Years of Age (Walter, November 2021).

Overall, in this interim combined analysis of a Phase I dosage-escalation study and a Phase 2/3 randomized placebo-controlled efficacy trial of BNT162b2 in children aged 5-11 years, a 10 mcg dose of the vaccine elicited robust antibody responses, was effective at preventing symptomatic COVID-19 and was safe at a median time to follow-up of approximately 2 months.

Study population:  

  • In a Phase 1 multicenter dosage-escalation study, 48 healthy children who were 5-11 years of age received escalating doses of BNT162b2.
  • In a Phase 2/3 multicenter randomized placebo-controlled efficacy trial, 2,285 participants who were 5-11 years of age from 81 sites in the U.S., Spain, Finland and Poland who were either healthy or had stable chronic medical conditions underwent 2:1 randomization.
  • 2,268 received injections (1,517 received BNT162b2 at a dose of 10 mcg, and 751 received a saline placebo) — 97% of participants received both doses of the vaccine.
  • Approximately half the participants were male.
  • 79% of participants were White and 6% were Black; 8% of the Phase I participants were Hispanic or Latinx, compared with 21% of the Phase 2/3 participants who were Hispanic or Latinx.
  • The median follow-up period was 2.3 months.

Key findings:  

  • In the dosage-escalation study, fever was more common in the 30 mcg subgroup compared with the groups that received 10 mcg or 20 mcg of BNT162b2; in fact, after the four sentinel subjects received a second dose of 30 mcg of BNT162b2, the internal review committee recommended that the other participants in that group receive 10 mcg as their second dose.
  • Neutralizing antibody titers were similar between the 10 mcg and 20 mcg subgroups in the dosage-escalation study, which is why the 10 mcg dose was selected for the Phase 2/3 trial.
  • In the Phase 2/3 study, the most common adverse events included injection site pain (71-74% of BNT162b2 recipients after dose one), fatigue, headache and muscle aches, most resolved within 1-2 days.
  • Fever (temperature ≥38 C) was reported by 8.3% of vaccine recipients after the first or second dose. Fever ≥40 C occurred in only one participant. 
  • Systemic adverse events were more common after dose two compared with dose one of the vaccine.
  • Immune responses to 10 mcg of BNT162b2 vaccine among children aged 5-11 years were similar to a parallel cohort of individuals aged 16-25 years that received 30 mcg of BNT162b2, regardless of prior SARS-CoV-2 infection status.
  • Overall vaccine efficacy of BNT162b2 was 90.7% against COVID-19 disease in individuals aged 5-11 years (95% CI, 67.4-98.3). There were three cases of COVID-19 in the vaccine group, and 16 cases in the placebo group.
  • There were no cases of severe COVID-19 during the study.

Limitations:  

  • Limited follow-up, so durability of antibody responses and efficacy remains unknown — analysis is ongoing.
  • Low racial and ethnic diversity of study population.
  • Small sample size, so infrequent adverse events (such as allergic reactions or myocarditis/pericarditis) may not have been observed.

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine through 6 Months (Thomas, September 2021). 

This was a pre-specified follow-up analysis of safety and efficacy data of a Phase 2/3 randomized placebo-controlled efficacy trial of BNT162b2 through approximately 6 months. In this analysis the vaccine demonstrated sustained effectiveness against severe COVID-19 (96.7%, 95% confidence interval 80.3-99.9), but a gradual decline in effectiveness against symptomatic infection was observed.  

Study population:   

  • In a Phase 2/3 multinational randomized placebo-controlled efficacy clinical trial, 44,165 participants over 16 years of age from 152 sites worldwide who were either healthy or had stable chronic medical conditions underwent 1:1 randomization. 
  • This analysis also included data from another multinational randomized placebo-controlled trial of individuals aged 12-15 years.    
  • 43,409 received both doses of the vaccine.   
  • 21,759 received two doses of BNT162b2, and 21,650 received a saline placebo.   
  • 55% of subjects in the BNT162b2 group had at least 6 months of follow-up data. The individuals aged 12-15 years did not contribute to the longitudinal analysis of vaccine efficacy because they had not completed 6 months of follow-up. 

 Key findings:   

  • Overall vaccine efficacy of BNT162b2 was 91.3% against COVID-19 disease in individuals aged 12 years and older (95% CI, 89.0-93.2).     
  • Similar vaccine efficacy was observed across subgroups defined by age, sex, race, ethnicity, baseline body mass index and the presence of coexisting conditions.     
  • There were 30 episodes of severe COVID-19 in the placebo group, and only one in the BNT162b2 group, corresponding to a vaccine efficacy against severe disease of 96.7% (95% CI, 80.3 to 99.9).     
  • Observed vaccine efficacy declined over time based on time since vaccination, falling from 96.2% (95% CI, 93.3-98.1) through 2 months after the second dose, to 90.1% (95% CI, 86.6-92.9) between 2 and 4 months after the second dose, to 83.7% (95% CI, 74.7-89.9) at >4 months after the second dose until the data cutoff date.    

 Limitations:   

  • Data for the longitudinal analysis of vaccine efficacy was not stratified by subgroup, so it is unclear which populations are contributing most to the observed waning of efficacy over time.  
  • No longitudinal efficacy data for individuals aged 12-15 years – this analysis is ongoing. 
  • The follow-up period did not include time when the Delta variant was predominant. 

Safety, Immunogenicity, and Efficacy of the BNT162b2 Covid-19 Vaccine in Adolescents (Frenck, July 2021). 

Overall, in this interim analysis of a Phase 2/3 randomized placebo-controlled efficacy trial of BNT162b2 in adolescents aged 12-15 years, the vaccine elicited robust antibody responses and was effective at preventing symptomatic COVID-19 and was safe at a median time to follow-up of 2 months.  

 Study population:   

  • In a Phase 2/3 multicenter randomized placebo-controlled efficacy clinical trial, 2,264 participants aged 12-15 years of age from 29 sites in the U.S. who were either healthy or had stable chronic medical conditions underwent 1:1 randomization. 
  • 2,260 received injections (1,131 received BNT162b2, and 1,129 received a saline placebo) – 97% of participants received both doses of the vaccine. 
  • 51% of participants were male. 
  • 86% of participants were White, and 12% were Hispanic or Latinx. 
  • 58% of subjects in the BNT162b2 group had at least 2 months of follow-up data. 

 Key findings:   

  • The most common adverse events included injection site pain (86% of BNT162b2 recipients after dose 1), fatigue, headache and muscle aches – most resolved within 1-2 days. 
  • Fever (temperature ≥38°C) was reported after the second dose by 20% of vaccine recipients, but fever ≥40°C occurred in only one participant.   
  • Systemic adverse events were more common after dose 2 compared with dose 1 of the vaccine. 
  • Immune responses to BNT162b2 vaccine were more robust in adolescents aged 12-15 years compared with data from a parallel cohort of individuals aged 16-25 years, regardless of prior SARS-CoV-2 infection status. 
  • Overall vaccine efficacy of BNT162b2 was 100% against COVID-19 disease in individuals aged 12-15 years (95% CI, 75.3-100) – there were no cases of COVID-19 in the vaccine group. 
  • There were no cases of severe COVID-19 during the study.   

 Limitations:   

  • Limited follow-up so durability of antibody responses and efficacy remains unknown – analysis is ongoing. 
  • Low racial and ethnic diversity of study population. 
  • Small sample size so infrequent adverse events (such as allergic reactions or myocarditis/pericarditis) may not have been observed. 

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine (Polack, December 2020).   

Overall, in this interim analysis of a Phase 2/3 randomized placebo-controlled efficacy trial, BNT162b2 was effective at preventing symptomatic COVID-19 and was safe at a median time to follow-up of 2 months.  

Study population:   

  • In a Phase 2/3 multinational randomized placebo-controlled efficacy clinical trial, 43,538 participants over 16 years of age from 152 sites worldwide who were either healthy or had stable chronic medical conditions underwent 1:1 randomization.   
  • 43,448 received injections.   
  • 21,720 received two doses of BNT162b2, and 21,728 received a saline placebo.   
  • Patients with prior known COVID-19, on immunosuppressive therapy, who had an immunocompromising condition or who were pregnant were excluded. People with well-controlled HIV infection were included.   
  • 3% of participants had serologic evidence of prior COVID-19 at the time of enrollment (but would have had asymptomatic disease, per enrollment exclusion criteria).  

 Primary endpoints:   

  • Efficacy: The efficacy of BNT162b2 against confirmed COVID-19 with onset at least 7 days after the second dose in participants who had been without serologic or virologic evidence of SARS-CoV-2 infection up to 7 days after the second dose; efficacy in participants with and participants without evidence of prior infection.   
  • Confirmed COVID-19 was defined as having a positive RT-PCR respiratory specimen for SARS-CoV-2 AND at least one of the following: fever, new or increased cough, new or increased shortness of breath, chills, new or increased muscle pain, new loss of taste or smell, sore throat, diarrhea or vomiting.  
  • Safety: Solicited local or systemic adverse events and use of an antipyretic or pain medication within 7 days of receiving either the vaccine or placebo via an electronic diary in a “reactogenicity” subset of patients; unsolicited adverse events reported through 1 month after the second dose of vaccine; unsolicited adverse events through 6 months after the second dose.   
  • 196 people living with HIV were included in the trial, but their safety data are being analyzed separately and have not yet been reported.   
  • 2-month follow-up data were available for 37,706 participants; in the reactogenicity subset, data were available for 8,183 participants.   

 Key findings:   

Efficacy:   

  • As of the writing of the report, 36,523 participants with no serologic or virologic evidence of existing or prior SARS-CoV-2 infection could be evaluated for efficacy at least 7 days after the second dose.    
  • As of the writing of the report, 40,137 participants with and without prior infection could be evaluated at least 7 days after the second dose.   
  • At the time of analysis, 3,614 participants had serologic evidence of COVID-19.    
  • Per information shared with FDA, 1,747 people in the vaccinated group had positive serology for SARS-CoV-2, compared to 1,847 in the placebo group.   
  • In the 37,706 participants who had a median of at least 2 months of safety data available after the second dose:     
  • The median age was 52 years, and 42% of participants were older than 55 years.     
  • 83% were White, 9% were Black or African American, and 28% were Hispanic or Latinx.     
  • 35% were obese (BMI≥ 30.0 kg/m2), and 21% had at least one coexisting condition.     
  • Among 36,523 participants who had no serologic or virologic evidence of existing or prior SARS-CoV-2 infection, there were eight cases of COVID-19 with onset at least 7 days after receiving the second dose of BNT162b2, and 162 cases with onset at least 7 days after receiving the second dose of placebo.   
  • BNT162b2 was 95% effective in preventing COVID-19 disease (95% CI, 90.3-97.6).     
  • Similar vaccine efficacy (generally 90% -100%) was observed across subgroups defined by age, sex, race, ethnicity, baseline BMI and the presence of coexisting conditions.     
  • Among the 40,137 participants with and without evidence of prior infection, nine cases occurred with onset at least 7 days after receiving the second dose of BNT162b2, and 169 cases occurred with onset at least 7 days after receiving the second dose of placebo.     
  • BNT162b2 was 94.6% effective in preventing COVID-19 disease in this group (95% CI, 89.9-97.3).    
  • Of the 3,614 participants who had serologic evidence of COVID-19 at the time of analysis, there were nine cases of COVID-19 disease in the placebo group and 10 in the vaccinated group.    
  • When examining rates of disease after the first dose of vaccine and before the second, there were 39 cases in the vaccinated group and 82 in the placebo group, resulting in a 52.4% efficacy rate after one dose (95% CI, 29.5-68.4).   

 Safety:   

  • The safety analysis included all participants who had received at least one dose of the vaccine or placebo.   
  • In the reactogenicity subset, among those aged 16-55 years:   
  • Approximately 93% of those who received BNT162b2 had mild-to-moderate pain, redness or swelling at the infection site after dose 1, and 88% experienced these symptoms after dose 2. Approximately 15% of these events occurred in the placebo group after dose 1 and 13% after dose 2.  
  • In the reactogenicity subset, among those aged 55 years or more:   
  • Approximately 82% of those who received BNT162b2 had mild-to-moderate pain, redness or swelling at the infection site after dose 1; 79% experienced these symptoms after dose 2. Approximately 11% of these events occurred in the placebo group after dose 1 and 9% after dose 2.   
  • In vaccine recipients, the most commonly reported systemic events were fatigue and headache (59% after the first dose and 52% after the second dose among younger vaccine recipients, aged 16-55 years; 51% after the first dose and 39% after the second dose among older recipients, aged >55 years).  
  • Fatigue and headache were also reported by many placebo recipients (23% after the first dose and 24% after the second dose among younger vaccine recipients; 17% after the first dose and 14% after the second dose among older recipients).   
  • Fever (temperature ≥38°C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients.   
  • The incidence of serious adverse events was similar in the vaccine and placebo groups (0.6% and 0.5%, respectively).   
  • Among 21,621 people in the trial who received BNT162b2, four related serious adverse events were reported: shoulder injury related to vaccine administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia and right leg paresthesia.    
  • Four participants in the clinical trial who received the vaccine later developed Bell’s palsy. These cases occurred at 3, 9, 37 and 48 days after vaccination. The observed frequency of reported Bell’s palsy in the vaccine group is consistent with the expected background rate in the general population, according to FDA.  
  • No deaths were considered by the investigators to be related to the vaccine or placebo.     

Limitations:   

  • The report includes 2 months of follow-up after the second dose of the vaccine for only half of the trial participants.    
  • The primary efficacy endpoint was clinical disease; asymptomatic infection was not assessed, although additional data utilizing a serologic endpoint are being collected.  
  • The trial did not include children, immunocompromised people or pregnant women, but other studies are being conducted to assess BNT162b2 in these groups.   
  • While there was a small group of people with evidence of prior COVID-19 infection at the time of analysis, the number of cases in this group was too small to draw any conclusions about the efficacy of the vaccine in individuals with prior infection  
  • Serial RT-PCR testing was not performed, and so the efficacy of the vaccine in potentially preventing spread of SARS-CoV-2 could not be determined.     

Effectiveness of BNT162b2 Vaccine Against Delta Variant in Adolescents (Reis, November 2021).

This was an observational cohort study designed to evaluate the performance of the Pfizer-BioNTech COVID-19 vaccine against symptomatic COVID-19 among adolescents aged 12-18 years in Israel using data from Clalit Health Services, the largest health care organization in Israel, over the time period June 8 to Sept. 14, 2021, when the Delta variant was predominant. The investigators identified 94,354 vaccine recipients and matched them to 94,354 unvaccinated controls; baseline demographic and clinical characteristics were similar between the two groups. The median follow-up was 27 days after the first dose. In this analysis, vaccine effectiveness against symptomatic COVID-19 was 57% (95% CI, 39-71) on days 14 to 20 after the first dose, 82% (95% CI, 73-91) on days 21 to 27 after the first dose and 93% (95% CI, 88-97) on days 7 to 21 after the second dose.

Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months (Levin, October 2021). 

This was a prospective 6-month longitudinal immunogenicity study in a cohort of health care workers aged 18 years and older at Sheba Medical Center in Israel who received two doses of the Pfizer-BioNTech COVID-19 vaccine. Individuals were eligible to participate only if they had no history of SARS-CoV-2 infection prior to vaccination (based on a negative anti–SARS-CoV-2 IgG test or the absence of a positive PCR test for SARS-CoV-2, with no history of suspected clinical SARS-CoV-2 infection). Both anti-spike IgG and neutralizing antibodies were measured monthly. 

A total of 4,868 individuals were enrolled. The mean age of the participants was 46.9 years (standard deviation, ±13.7). Antibody titers reached their peak between days 4 and 30 after the second dose of vaccine, then consistently declined over the entire study period, ultimately decreasing by a factor of 18.3 after 6 months. Neutralizing antibodies also decreased, but the rate of decline slowed after 3 months. There were no differences in IgG antibody decay kinetics by age or sex, but older individuals (age 65 years and up) had lower antibody levels at all time points and demonstrated a faster decrease in neutralizing antibodies up to 3 months. Factors associated with lower IgG titers included older age, male sex, the presence of two or more coexisting conditions (i.e., hypertension, diabetes, dyslipidemia, or heart, lung, kidney or liver disease), the presence of autoimmune disease and the presence of immunosuppression. 

Effectiveness of Pfizer-BioNTech mRNA Vaccination Against COVID-19 Hospitalization Among Persons Aged 12–18 Years — United States, June–September 2021 (Olson, October 2021).

In this analysis, the investigators used a test-negative design to assess the performance of two doses of the Pfizer-BioNTech COVID-19 vaccine against pediatric hospitalization for COVID-19 using data on pediatric hospitalizations from 19 pediatric hospitals in 16 states over the time period June 1–Sept. 30, 2021, when Delta was the predominant SARS-CoV-2 variant. They identified 464 patients for analysis, which included 179 case patients and 285 controls. Of the 179 case patients, 97% were unvaccinated. Seventy-seven case patients (43%, all unvaccinated) required ICU admission, of which 29 required invasive mechanical ventilation, vasoactive infusions or extracorporeal membrane oxygenation, and of whom two died. None of the vaccinated case patients required ICU admission and none died. Overall vaccine effectiveness against COVID-19 hospitalization was 93% (95% CI, 83–97).

Effectiveness of mRNA BNT162b2 COVID-19 Vaccine up to 6 months in a Large Integrated Health System in the USA: a Retrospective Cohort Study (Tartof, October 2021).

This was a large retrospective population-based cohort study using data from the Kaiser Permanente Southern California (U.S.) health care system designed to evaluate the longitudinal effectiveness of the Pfizer-BioNTech COVID-19 vaccine against SARS-CoV-2 infections and COVID-19-related hospital admissions. The study included data from Dec. 14, 2020, to Aug. 8, 2021. During part of the follow-up period (March 4-July 21, 2021), all positive SARS-CoV-2 specimens were also submitted for genome sequencing and viral lineage description. The investigators computed SARS-CoV-2 variant-specific estimates of vaccine effectiveness stratified by time since vaccination to determine the independent effects of waning immunity and emergence of novel variants (i.e., Delta) on vaccine effectiveness. Data from a total of 3,436,957 individuals was included in the analysis, of whom 1,146,768 (33.4%) had received one or more doses of BNT162b2 (1,010,516 received ≥1 dose of the Moderna COVID-19 vaccine, and 109,911 received a dose of the Johnson & Johnson/Janssen COVID-19 vaccine and 1,166,790 were unvaccinated). Over the entire time period, overall vaccine effectiveness against SARS-CoV-2 infection due to non-Delta variants was 91% (95% CI, 88-92) and 75% (95% CI, 71-78) against infections due to Delta variant. Vaccine effectiveness was highest in the first month after vaccination but fell by 4 months after vaccination (from 97% to 67% against non-Delta variants, and from 93% to 53% against Delta variant). The rate of decline was not different by virus variant. Importantly, vaccine effectiveness against hospital admissions remained stable throughout the study time period.

COVID-19 Vaccine Coverage in Health-Care Workers in England and Effectiveness of BNT162b2 mRNA Vaccine Against Infection (SIREN): A prospective, Multicentre, Cohort Study (Hall, May 2021).  

The goal of this prospective cohort study of UK health care workers and support staff was to evaluate the effectiveness of that country’s vaccination rollout, including its decision to permit a delay of up to 12 weeks in administrating the second dose of authorized COVID-19 vaccines. A total of 29,378 participants enrolled in the study, of whom 23,324 workers from 104 hospitals were included in the analysis. This cohort included 8,203 individuals (35%) with a prior history of SARS-CoV-2 infection (prior positive antibody or PCR, or seropositive at baseline) and 15,121 (65%) with no history of infection. A majority of the cohort was female (N=19,692, 84%), under age 65 (N=22,955, 98%) and without underlying medical conditions (N=17,450, 75%). By the end of the study period, vaccine coverage in the cohort had reached 89%, with 94% (N=19,384) of vaccinated cohort members receiving the Pfizer-BioNTech COVID-19 vaccine and the remainder receiving the Oxford-AstraZeneca COVID-19 vaccine. Only 1,607 (8%) received both doses by the end of the study follow-up period. Vaccine effectiveness against SARS-CoV-2 infection starting 21 days after the first dose of Pfizer-BioNTech COVID-19 vaccine was 70% (95% CI, 53-87), which increased to 85% (95% CI, 74-96) starting 7 days after the second dose. There were 51 asymptomatic infections in the unvaccinated cohort compared with 10 in the vaccinated cohort, suggesting protection against asymptomatic infection. 

Safety 

For up-to-date Pfizer-BioNTech COVID-19 vaccine safety considerations, refer to the Contraindications and Precautions section of CDC’s Interim Clinical Considerations for Use of COVID-19 Vaccines

 

Dosing & Administration  

For current overview including guidance on additional doses, refer to our Vaccine Dosing & Schedule page. 

 

Moderna COVID-19 Vaccine  

Overview 

The vaccine, mRNA-1273, was fully approved by FDA in January 2022 for individuals 18 years of age and older. It currently also has emergency use authorization for children 6 months–17 years of age.

 

Literature 

Efficacy of the mRNA-1273 SARS-CoV-2 Vaccine at Completion of Blinded Phase (El Sahly, September 2021). 

This was the final analysis of safety and efficacy data of the blinded phase of a Phase 3 randomized placebo-controlled efficacy trial of mRNA-1273 through approximately 5 months. In this analysis the vaccine demonstrated sustained effectiveness against both symptomatic and severe COVID-19 (>90%) regardless of time since vaccination, as well as efficacy against asymptomatic infection.  

 Study population:   

  • In a Phase 3 multicenter randomized placebo-controlled efficacy clinical trial, 30,415 participants over 18 years of age from 99 sites in the U.S. who were either healthy or had stable chronic medical conditions underwent 1:1 randomization. 
  • 29,362 received both doses of the vaccine.   
  • 14,635 received two doses of mRNA-1273, and 14,727 received a saline placebo.   
  • The median duration of follow-up after dose 2 of the vaccine was 183 days. 

 Key findings:   

  • Overall vaccine efficacy of BNT162b2 was 93.2% against COVID-19 disease in individuals aged 18 years and older (95% CI, 89.0-93.2).     
  • Similar vaccine efficacy was observed across subgroups defined by age, sex, race, ethnicity, baseline BMI and the presence of coexisting conditions.     
  • There were 106 episodes of severe COVID-19 in the placebo group and only two in the mRNA-1273 group, corresponding to a vaccine efficacy against severe disease of 98.2% (95% CI, 92.8-99.6).     
  • Observed vaccine efficacy remained stable over time based on time since vaccination, and was 91.8% (95% CI, 86.9-95.1) through 2 months after the second dose, 94.0% (95% CI, 91.2- 96.1) between 2 and 4 months after the second dose, and 92.4% (95% CI, 84.3-96.8) at >4 months after the second dose until the data cutoff date. 
  • Vaccine efficacy against asymptomatic infection – determined by detection of anti-nucleocapsid antibodies or a positive SARS-CoV-2 PCR in the absence of symptoms of COVID-19 – was 63.0% (95% CI, 56.6-68.5). 
  • There were no new safety signals – there were eight cases of Bell’s palsy in the mRNA-1273 group (three in the placebo group), no cases of myocarditis, two cases of pericarditis in both groups and two cases of anaphylaxis in both groups. 

 Limitations:   

  • The follow-up period did not include time when the Delta variant was predominant. 
  • The trial did not include children, immunocompromised people or pregnant women, but other studies are being conducted to assess mRNA-1273 in these groups. 

 

Evaluation of mRNA-1273 SARS-CoV-2 Vaccine in Adolescents (Ali, August 2021). 

Overall, in this interim analysis of a Phase 2/3 randomized placebo-controlled efficacy trial of mRNA-1273 in adolescents aged 12-17 years, the vaccine elicited robust antibody responses and was effective at preventing symptomatic COVID-19 and was safe at a median time to follow-up of 2 months.  

 Study population:   

  • In a Phase 2/3 multicenter randomized placebo-controlled efficacy clinical trial, 3,732 participants aged 12-17 years of age from 26 sites in the U.S. who were either healthy or had stable chronic medical conditions underwent 2:1 randomization. 
  • 2,489 were randomized to receive mRNA-1273, and 1,243 were randomized to receive a saline placebo) – 98% of participants received both doses of the vaccine. 
  • 51% of participants were male. 
  • 84% of participants were White, and 12% were Hispanic or Latinx.   
  • The median duration of follow-up from randomization to the data cutoff date was 83 days (and 53 days from second dose to data cutoff). 

 Key findings:   

  • The most common adverse events included injection site pain (93.1% of mRNA-1273 recipients after dose 1), fatigue, headache and muscle aches. 
  • Fever (temperature ≥38°C) was more common after dose 2 of mRNA-1273, but grade 3 fever was only reported in 46 participants (2.7%), and grade 4 fever was reported in only one participant.   
  • Solicited local and systemic adverse events persisted for a mean of 4 days. 
  • There were no cases of myocarditis or pericarditis. 
  • Immune responses to mRNA-1273 vaccine in adolescents aged 12-17 years were similar to those from a parallel cohort of individuals aged 18-25 years. 
  • Overall vaccine efficacy of mRNA-1273 could not be assessed using protocol-defined endpoints because of the small number of cases (zero cases in the mRNA-1273 group, and four in the placebo group) – using CDC definitions for COVID-19 illness, vaccine efficacy 93.3% (95% CI, 47.9-99.9). 
  • There were no cases of severe COVID-19 during the study.     

 Limitations:   

  • Limited follow-up so durability of antibody responses and efficacy remains unknown – analysis is ongoing. 
  • Low racial and ethnic diversity of study population. 
  • Small sample size so infrequent adverse events (such as allergic reactions or myocarditis/pericarditis) were not observed. 

 

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine (Baden, December 2020).  

Overall, in this Phase 3 randomized, stratified, double-blind, placebo-controlled trial, mRNA-1273 was effective at preventing symptomatic COVID-19 and was safe at a median time to follow-up of 2 months.    

 Study population:   

  • mRNA-1273-P301 is a Phase 3 ongoing randomized, stratified, double-blind, placebo-controlled trial.   
  • 30,420 participants over 18 years of age from 99 sites in the U. S. were randomized in a 1:1 manner to receive injections of either the mRNA-1273 (N=15,210) or a saline placebo (N=15,210) on day 1 and day 29.   
  • More than 96% of participants received both injections.  
  • 66.3% of the study population was comprised of patients 18-64 years of age with risk for progression to severe COVID-19 and patients  ≥65 years of age.     
  • Patients were considered to have risk for severe disease if they had any of the following comorbidities: diabetes, chronic lung disease, severe obesity, significant cardiovascular disease, liver disease or well-controlled HIV (persons with poorly controlled HIV were not included in the trial).  
  • There were 179 patients living with HIV in the trial; data on this specific group have not yet been reported.    
  • The mean age of the participants was 51.4 years, 47.3% of the participants were female, 24.8% were  ≥65 years of age, and 16.7% were younger than 65 years of age and had predisposing medical conditions that put them at risk for severe COVID-19.   
  • The majority of participants were White (79.2%); 10.2% of participants were African American, and 20.5% were Hispanic/Latinx.   
  • Patients had a negative SARS-CoV-2 status at baseline (with a negative RT-PCR and negative serology against the SARS-CoV-2 nucleocapsid at day 1).     
  • 2.2% of study participants had serologic evidence of prior COVID-19.   
  • Participants were excluded if they were pregnant or breastfeeding, pediatric, immunocompromised or had a known history of SARS-CoV-2.   
  • The interim primary efficacy analysis was based on the Per-Protocol Set, which consisted of 28,207 participants with negative baseline SARS-CoV-2 status and who received two doses of investigational product per schedule with no major protocol deviations.   
  • The set included 14,134 patients in the vaccine group and 14,073 patients in the placebo group.   

 Primary endpoints:   

  • Efficacy: The reduction of incidence of COVID-19 among participants without evidence of SARS-CoV-2 infection before the first dose of vaccine in the period after 14 days post-dose 2.   
  • The case definition of confirmed COVID-19 was:    
  • At least two of the following systemic symptoms: Fever (>38°C), chills, myalgia, headache, sore throat, new olfactory and taste disorder(s) or at least one of the following respiratory signs/symptoms: cough, shortness of breath or difficulty breathing, OR clinical or radiographic evidence of pneumonia; and   
  • Nasopharyngeal swab, nasal swab or saliva sample (or respiratory sample, if hospitalized) positive for SARS-CoV-2 by RT-PCR.   
  • Safety: To describe the safety of mRNA-1273 after one or two doses.     
  • Solicited events: participants recorded local reactions, systemic events and antipyretic/pain medication usage from day 1 through day 7 after each dose.   
  • Unsolicited adverse events were collected from dose 1 to 28 days after the last dose.    
  • Medically attended adverse events and serious adverse events were also collected from dose 1 to the end of the study.   

 Key findings:   

 Efficacy:   

  • Risk and demographics at baseline were reported in N=15,181 individuals receiving the vaccine and N=15,170 receiving placebo.    
  • At least one high-risk condition for severe COVID-19 was present in 27.1% of participants.    
  • There were no differences in demographics in the vaccine and placebo groups.    
  • As of Nov. 25, 2020, the participants had a median follow-up duration of 64 days (range, 0-97) after the second dose, with 61% of participants having more than 56 days of follow-up.   
  • After day 1 and through Nov. 25, 2020, a total of 269 COVID-19 cases were identified, with an incidence of 79.8 cases per 1,000 person-years (95% CI, 70.5-89.9) among participants in the placebo group with no evidence of previous SARS-CoV-2 infection. Subgroup analyses of the primary efficacy endpoint showed similar efficacy across age groups, genders, racial and ethnic groups and participants with medical comorbidities associated with high risk of severe COVID-19.    
  • For the primary analysis, 196 cases of COVID-19 were diagnosed: 11 cases in the vaccine group (3.3 per 1,000 person-years; 95% CI, 1.7-6.0) and 185 cases in the placebo group (56.5 per 1,000 person-years; 95% CI, 48.7-65.3), indicating 94.1% efficacy of the mRNA-1273 vaccine (95% CI, 89.3-96.8; p<0.001) for the prevention of symptomatic SARS-CoV-2 infection as compared with placebo.    
  • Findings were similar across key secondary analyses including assessment starting 14 days after dose 1 (225 cases with placebo vs. 11 with mRNA-1273, indicating a vaccine efficacy of 95.2% [95% CI, 91.2-97.4]) and assessment including participants who were SARS-CoV-2 seropositive at baseline in the per-protocol analysis (187 cases with placebo vs. 12 with mRNA-1273; one volunteer assigned to receive mRNA-1273 was inadvertently given placebo), indicating a vaccine efficacy of 93.6% (95% CI, 88.6- 96.5).    
  • Between days 1 and 42, seven cases of COVID-19 were identified in the mRNA-1273 group, as compared with 65 cases in the placebo group.   
  • A key secondary endpoint evaluated the efficacy of mRNA-1273 at preventing severe COVID-19.     
  • 30 participants in the trial had severe COVID-19; all 30 were in the placebo group (indicating vaccine efficacy of 100% [95% CI, could not be estimated to 1.0]), and one death among these participants was attributed to COVID-19.   
  • Among participants who were positive for SARS-CoV-2 by serologic or virologic testing at baseline (337 in the placebo group and 343 in the mRNA-1273 group), one case of COVID-19 was diagnosed by RT-PCR testing in a placebo recipient, and no cases were diagnosed in mRNA-1273 recipients.    
  • Among participants who were negative for SARS-CoV-2 at baseline (by RT-PCR or antibody testing), in addition to symptomatic COVID-19 cases, 39 (0.3%) in the placebo group and 15 (0.1%) in the mRNA-1273 group had nasopharyngeal swabs that were positive for SARS-CoV-2 by RT-PCR at the second dose visit (surveillance swab) but had no evidence of COVID-19 symptoms.   

 Safety:   

  • Safety data at the time of the interim analysis were available for 30,347 participants, with a median follow-up of 2 months.  
  • Solicited adverse events at the injection site occurred more frequently in the mRNA-1273 group than in the placebo group after both the first dose (84.2% vs. 19.8%) and the second dose (88.6% vs. 18.8%).  
  • In the mRNA-1273 group, injection-site events were mainly grade 1 or 2 in severity and lasted a mean of 2.6 and 3.2 days after the first and second doses, respectively.   
  • The most common injection-site event was pain after injection (86.0%).  
  • Delayed injection-site reactions (those with onset on or after day 8) were noted in 244 participants (0.8%) after the first dose and in 68 participants (0.2%) after the second dose.  
  • Reactions were characterized by erythema, induration and tenderness, and they resolved over the following 4 to 5 days.  
  • Solicited systemic adverse events occurred more often in the mRNA-1273 group than in the placebo group after both the first dose (54.9% vs. 42.2%) and the second dose (79.4% vs. 36.5%).   
  • The severity of the solicited systemic events increased after the second dose in the mRNA-1273 group, with an increase in proportions of grade 2 events (from 16.5% after the first dose to 38.1% after the second dose) and grade 3 events (from 2.9% to 15.8%).  
  • Solicited systemic adverse events in the mRNA-1273 group lasted a mean of 2.6 days and 3.1 days after the first and second doses, respectively.  
  • Both solicited injection-site and systemic adverse events were more common among younger participants (18 to <65 years of age) than among older participants (≥65 years of age).  
  • Solicited adverse events were less common in participants who were positive for SARS-CoV-2 infection at baseline than in those who were negative at baseline.  
  • The frequency of unsolicited adverse events, unsolicited severe adverse events and serious adverse events reported during the 28 days after injection was generally similar among participants in the two groups.  
  • 3 deaths occurred in the placebo group (one from intra-abdominal perforation, one from cardiopulmonary arrest and one from severe systemic inflammatory syndrome in a participant with chronic lymphocytic leukemia and diffuse bullous rash) and two in the vaccine group (one from cardiopulmonary arrest and one by suicide).  
  • The frequency of grade 3 adverse events in the placebo group (1.3%) was similar to that in the vaccine group (1.5%), as were the frequencies of medically attended adverse events (9.7% vs. 9.0%) and serious adverse events (0.6% in both groups).  
  • Hypersensitivity reactions were reported in 1.5% and 1.1% of participants in the vaccine and placebo groups, respectively.  
  • Bell’s palsy occurred in the vaccine group (three participants [<0.1%]) and the placebo group (one participant [<0.1%]) during the observation period of the trial (more than 28 days after injection).  
  • No evidence of vaccine-associated enhanced respiratory disease was noted, and fewer cases of severe COVID-19 or any COVID-19 were observed among participants who received mRNA-1273 than among those who received placebo.  
  • Adverse events that were deemed by the trial team to be related to the vaccine or placebo were reported among 4.5% of participants in the placebo group and 8.2% in the mRNA-1273 group.   
  • The most common treatment-related adverse events (those reported in at least 1% of participants) in the placebo group and the mRNA-1273 group were fatigue (1.2% and 1.5%) and headache (0.9% and 1.4%).  
  • In the overall population, the incidence of treatment-related severe adverse events was higher in the mRNA-1273 group (71 participants [0.5%]) than in the placebo group (28 participants [0.2%]).   
  • The relative incidence of these adverse events according to vaccine group was not affected by age.   

Limitations:   

  • The primary efficacy endpoint was clinical disease; asymptomatic infection was not assessed, although additional data utilizing a serologic endpoint are being collected.   
  • The trial did not include children, immunocompromised people or pregnant women, but other studies are being conducted to assess mRNA-1273 in these groups.    
  • While there was a small group of people with evidence of prior COVID-19 infection at the time of analysis, the number of cases in this group was too small to draw any conclusions about the efficacy of the vaccine in individuals with prior infection; this may change as the trial continues.   
  • Serial RT-PCR testing was not performed, and so the efficacy of the vaccine in potentially preventing spread of SARS-CoV-2 could not be determined.    

  

Safety and Immunogenicity of SARS-CoV-2 mRNA-1273 Vaccine in Older Adults (Anderson, December 2020).   

In this Phase 1 open-label trial of mRNA-1273 in 40 older adults, who were stratified according to age (56 to 70 years or ≥71 years), participants were assigned sequentially to receive two doses of either 25 μg or 100 μg of vaccine administered 28 days apart. Solicited adverse events were predominantly mild or moderate in severity and most frequently included fatigue, chills, headache, myalgia and pain at the injection site. Such adverse events were dose-dependent and were more common after the second immunization. By day 57, among the participants who received the 25-μg dose, the anti–S-2P geometric mean titer was 323,945 among those between the ages of 56-70 years and 1,128,391 among those who were >=71 years of age; among the participants who received the 100-μg dose, the geometric mean titer in the two age subgroups was 1,183,066 and 3,638,522, respectively. Binding- and neutralizing-antibody responses appeared to be similar to those previously reported among vaccine recipients between the ages of 18-55 years.  

 

Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19 (Doria-Rose, April 2021).   

In this Phase 1 open-label trial of mRNA-1273 in 33 healthy adults who received two injections of the vaccine 28 days apart, at a 209 day time point, geometric mean titers were: 92,451 (95% CI, 57,148- 149,562) in participants 18 to 55 years of age; 62,424 (95% CI, 36,765-105,990) in those 56 to 70 years of age; and 49,373 (95% CI, 25,171-96,849) in those 71 years of age or older. Serum neutralizing antibodies continued to be detected in nearly all the participants at day 209. The estimated half-life of binding antibodies starting 14 days after dose 2 (using an exponential decay model, which assumes a steady decay rate over time) was 52 days (95% CI, 46-58), and for neutralizing antibodies (using a power-law model, which assumes a decreasing decay rate over time) it was 173 days (95% CI, 144-225) for pseudovirus neutralization and 202 days (95% CI, 159-272) for live-virus neutralization.   

 

Safety 

For up-to-date Moderna COVID-19 vaccine safety considerations, refer to the Contraindications and Precautions section of CDC’s Interim Clinical Considerations for Use of COVID-19 Vaccines

 

Dosing & Administration

For a current overview including guidance on additional doses, refer to our Vaccine Dosing & Schedule page. 

 

Resources   

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