Booster Doses

FDA Takes Action on Updated mRNA COVID-19 Vaccines to Better Protect Against Currently Circulating Variants - September 11, 2023

Among adults aged ≥18 years without immunocompromising conditions, bivalent booster vaccine effectiveness (VE) against COVID-19–associated hospitalization declined from 62% at 7–59 days postvaccination to 24% at 120–179 days compared with VE among unvaccinated adults. Among immunocompromised adults, lower bivalent booster VE was observed. However, bivalent booster VE was sustained at 50% against critical COVID-19–associated outcomes, including intensive care unit admission or death. Estimates of Bivalent mRNA Vaccine Durability in Preventing COVID-19–Associated Hospitalization and Critical Illness Among Adults with and Without Immunocompromising Conditions — VISION Network, September 2022–April 2023 | MMWR (cdc.gov)

On September 1, 2022, the CDC issued new recommendations for COVID-19 boosters, after the FDA authorized updated booster formulas from both Pfizer-BioNTech and Moderna. These new boosters contain an updated bivalent formula that both boosts immunity against the original coronavirus strain and also protects against the newer Omicron variants that account for most of the current cases.

Everyone who is eligible should get an updated booster dose at least 2 months after their last COVID-19 shot—either since their last booster dose, or since completing their primary series.

The Moderna bivalent vaccine is authorized for use as:
•    A single booster dose in children 6 months through 5 years of age at least two months after completion of a primary series with the monovalent Moderna COVID-19 vaccine
•    A single booster dose in individuals 6 years of age and older at least two months after completion of either primary vaccination with any authorized or approved COVID-19 vaccine, or receipt of the most recent booster dose with any authorized or approved monovalent COVID-19 vaccine

The Pfizer-BioNTech bivalent vaccine is authorized for use as:
•    A single booster dose in children 6 months through 4 years of age at least 2 months after completion of primary vaccination with three doses of the monovalent Pfizer-BioNTech COVID-19 vaccine
•    A single booster dose in individuals 5 years of age and older at least two months after completion of either primary vaccination with any authorized or approved COVID-19 vaccine or receipt of the most recent booster dose with any authorized or approved monovalent COVID-19 vaccine

Initial Doses

Pfizer-BioNTech
  • On June 17, 2022 the FDA authorized emergency use for children ages 6 months to four years old; it had previously been authorized for individuals five years of age and older. In this age group, the vaccine is administered as a primary series of three doses in which the initial two doses are administered three weeks apart followed by a third dose administered at least eight weeks after the second dose.
  • On September 22, the FDA amended the emergency use authorization (EUA) to authorize a single booster dose for high-risk populations. On September 24, the CDC provided the following guidance:
    • people 65 years and older and residents in long-term care settings should receive a booster shot of Pfizer-BioNTech’s COVID-19 vaccine at least 6 months after their Pfizer-BioNTech primary series,
    • people aged 50–64 years with underlying medical conditions should receive a booster shot of Pfizer-BioNTech’s COVID-19 vaccine at least 6 months after their Pfizer-BioNTech primary series,
    • people aged 18–49 years with underlying medical conditions may receive a booster shot of Pfizer-BioNTech’s COVID-19 vaccine at least 6 months after their Pfizer-BioNTech primary series, based on their individual benefits and risks, and
    • people aged 18-64 years who are at increased risk for COVID-19 exposure and transmission because of occupational or institutional setting may receive a booster shot of Pfizer-BioNTech’s COVID-19 vaccine at least 6 months after their Pfizer-BioNTech primary series, based on their individual benefits and risks.
  • The FDA granted full approval for the Pfizer COVID-19 vaccine for individuals aged 16 years and older on August 23, 2021.
  • The FDA approved an additional dose of Pfizer vaccine for moderately to severely immunocompromised patients age 12 and above on August 12, 2021.  Additional information from CDC can be found here.
  • Pfizer’s vaccine is showing efficacy greater than 90%, and an emergency use authorization (EUA) was granted by the FDA on December 11, 2020. The FDA Briefing Document is available for review here. 
  • An EUA for adolescents aged 12-15 was granted by the FDA on May 10, 2021. View the patient fact sheet here. The CDC's ACIP met on May 12, 2021 to decide how it is to be used. View the ACIP's interim recommendation here. The ACIP analysis of the data from the clinical trial involving 2,200 adolescents noted efficacy of 100% against symptomatic infection. Immune responses were at least as high as those found in ages 16-25. There were 16 cases of COVID-19 in the trial, all in the placebo group. Pfizer has submitted an application for full authorization, and the FDA is expected to rule on the application by early September. 
  • A preliminary, non peer-reviewed article shows sera from patients who completed both doses of the Pfizer BioNTech vaccine had similar neutralizing geometric mean titers (GMTs) against SARS-CoV-2 engineered to contain the same mutations as the Alpha and Beta variants, compared to the wild-type, although the GMTs against the Beta variant were 19% lower. The authors note that the engineered viruses do not contain the full set of mutations present in the Alpha and Beta variants. 
Moderna
Janssen COVID-19 Vaccine
  • On June 1, the FDA revoked the emergency use authorization (EUA) of the Janssen COVID-19 Vaccine. On May 22, Janssen Biotech Inc. requested the voluntary withdrawal of the EUA for this vaccine. Janssen Biotech, Inc. informed the FDA that the last lots of the vaccine purchased by the U.S. Government have expired, there is no demand for new lots of the vaccine in the U.S., and they do not intend to update the strain composition of this vaccine to address emerging variants.
  • On May 6, 2022, the FDA announced that it has limited the authorized use of the Janssen COVID-19 vaccine to individuals 18 years of age and older for whom other authorized or approved COVID-19 vaccines are not accessible or clinically appropriate, and to individuals 18 years of age and older who elect to receive the Janssen COVID-19 vaccine because they would otherwise not receive a COVID-19 vaccine. This limitation is due to the rare but potentially life-threatening complication of Thrombosis with Thrombocytopenia Syndrome that occurs 1-2 weeks following vaccination.
  • Data was submitted to the FDA on October 5 for authorization for a booster shot for all patients 18 years and older.
  • At a Johns Hopkins/University of Washington COVID-19 conference held recently, J&J announced plans to study their vaccine in 12-17 year olds in the fall, plus three other studies involving 2-11 year olds, those younger than 2 years old, and immunocompromised and high risk children 1-17 years of age. 
  • Preliminary data from the Phase 3 ENSEMBLE vaccine trial was released on January 29, 2021. Among all participants from different geographies and including those infected with an emerging viral variant, Janssen’s COVID-19 single shot vaccine candidate was 66% effective overall in preventing moderate to severe COVID-19, 28 days after vaccination. 
  • The onset of protection was observed as early as Day 14. The level of protection against moderate to severe COVID-19 infection was 72% in the United States, 66% in Latin America and 57% in South Africa, 28 days post-vaccination. 
  • The vaccine candidate was 85% effective in preventing severe disease across all regions studied, 28 days after vaccination in all adults 18 years and older. 
  • The vaccine candidate demonstrated complete protection against COVID-related hospitalization and death, 28 days post-vaccination. 
  • The EUA was approved on February 27, 2021and the vaccine fact sheet is available here. The FDA briefing document is available here. 
  • Interim results from the phase 1-2a trial of the Johnson & Johnson vaccine were reported in the NEJM on January 13, 2021. This vaccine is a recombinant, replication-incompetent adenovirus 26 vector encoding a full length and stabilized SARS-CoV-2 spike protein. Results from two of three cohorts (18 to 55-year-olds and >/=65-year-olds) were reported. This trial examined the effects of single versus double dose, and low dose versus high dose. 
  • Neutralizing antibody titers were detected in 90% or more of all participants on day 29 after the first vaccine dose and reached 100% by day 57 in 18 to 55-year-olds with a further increase in titers, regardless of vaccine dose or age group. Titers remained stable until at least day 71 in the 18 to 55-year-olds, the latest time period in this study. A second dose provided an increase in titer by a factor of 2.6-2.9. Spike antibody titers were similar. On day 14, CD4+ T-cell responses were detected in 76 to 83% of the younger cohort, and 60 to 67% of the older cohort. CD8+ T cell responses followed a similar pattern. 
  • Adverse reactions were similar to current vaccines and occurred in 65 to 85% of recipients. The most common were fatigue, headache and myalgia. 
AstraZeneca
Novavax
  • NOVAVAX Releases Phase 3 Trial Data: Novavax (NVX-CoV2373) is a subunit vaccine made from a stabilized form of the spike protein using recombinant protein nanoparticle technology combined with a proprietary adjuvant.  The vaccine is administered as two doses, 21 days apart.  The phase 3 trial, called PREVENT-19 involved 30,000 adults in the US and Mexico, showed the vaccine to have *90.4% efficacy in preventing symptomatic disease, 100% efficacy in protection against moderate or severe disease and 91.0% efficacy in the elderly and those with comorbid conditions*.  This study took place when the alpha variant was predominant.  The trial has recently been expanded to include adolescents.  Local and systemic side effects were similar to the mRNA vaccines.  Novavax plans to apply for an EUA in September. NIH News Release (June 14, 2021) 
  • In preliminary results for Phase 2/3 trials, this adjuvated protein subunit vaccine showed up to 89.3% efficacy in the UK cohort and 85.6% efficacy against the UK variant but results from the South African cohort showed an efficacy of 60% in the HIV-negative population where 93% had the South African variant. 
Additional Vaccine Information
  • A study reported in MMWR on children 6 months to 5 years in the v-safe monitoring system following a third dose of mRNA vaccine found similar reactions which had been reported after the first two vaccines. Safety Monitoring of mRNA COVID-19 Vaccine Third Doses Among Children Aged 6 Months–5 Years — United States, June 17, 2022–May 7, 2023 | MMWR (cdc.gov)
  • This study in Pediatrics looked at data from safety surveillance in the Vaccine Safety Data Link (VSD) system (prospective data from 8 large health systems) on safety in approximately children under age 5 who had been given 250,000 doses of an mRNA vaccine. Risks were not elevated for any prespecified outcomes, including myocarditis/pericarditis. Safety of COVID-19 mRNA Vaccination Among Young Children in the Vaccine Safety Datalink | Pediatrics | American Academy of Pediatrics (aap.org) June 6, 2023
  • A prespecified interim analysis of a randomized clinical trial included 40,382 participants who received an inactivated vaccine series developed from either SARS-CoV-2 WIV04 (5 µg/dose) or HB02 (4 µg/dose) strains or an aluminum hydroxide–only control. The *efficacy for the 2 vaccines, compared with an aluminum hydroxide–only control, was 72.8% in the WIV04 group and 78.1% in the HB02 group*; both comparisons were statistically significant. Two severe cases of COVID-19 occurred in the alum-only group and none occurred in the vaccine groups.  This may be an answer for those who are waiting for a "more conventional vaccine. (Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial, May 26, 2021)  
  • This retrospective study among 95,000 VA patients during the Delta and Omicron periods found that vaccination was associated with lower odds of hospitalization, ICU admission, ventilation and death compared with no vaccination during both periods, although less so during the Omicron period, most likely due to overall less severity with Omicron infection. A third dose of mRNA vaccine was associated with additional risk reduction. Adverse outcomes of SARS-CoV-2 infection with delta and omicron variants in vaccinated versus unvaccinated US veterans: retrospective cohort study | The BMJ - May 23, 2023
  • In this decision analytical model using US population estimates, a simulation model revealed that booster campaigns achieving an uptake similar to seasonal influenza vaccination could have prevented an estimated 10 019 pediatric hospitalizations and 5 448 694 days of school absenteeism from October 1, 2022, to March 31, 2023. Estimated US Pediatric Hospitalizations and School Absenteeism Associated With Accelerated COVID-19 Bivalent Booster Vaccination | Infectious Diseases | JAMA Network Open | JAMA Network - May 19, 2023
  • A study in Scotland found that waning of the humoral response to vaccination was accelerated in those with obesity. Not only are such patients at higher risk of disease, but also more likely to require more frequent boosters. Accelerated waning of the humoral response to COVID-19 vaccines in obesity | Nature Medicine - May 11, 2023
  • A systematic review and meta-analysis of pooled randomized clinical trials found the incidence of Bell’s Palsy was significantly higher in vaccine vs. placebo patients. The risk of Bell’s Palsy with SARS-CoV-2 infection was even higher, however. Association of SARS-CoV-2 Vaccination or Infection With Bell Palsy: A Systematic Review and Meta-analysis | Facial Nerve | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network - April 27, 2023
  • Regarding Long-Term Immunity: The lay press has perhaps overstated the findings of this June 2021 study to be published in Nature.  The researchers studied plasmablasts (PB) in the peripheral blood and germinal center B (GC B) cells in lymph node biopsies from 14 volunteers.  Findings: Circulating IgG- and IgA-secreting PBs targeting the S protein peaked one week after the second immunization then declined, becoming undetectable three weeks later. These PB responses preceded maximal levels of serum anti-S binding and neutralizing antibodies to an early circulating SARS-CoV-2 strain as well as emerging variants, especially in individuals previously infected with SARS-CoV-2, who produced the most robust serologic responses. By examining fine needle aspirates (FNAs) of draining axillary LNs, they identified GC B cells that bound S protein in all participants sampled after primary immunization. Remarkably, high frequencies of S-binding GC B cells and PBs were sustained in these draining LNs for at least twelve weeks after the booster immunization. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses  
  • The NIH announced in April, 2021 a study assessing how people with immune system deficiencies or dysregulations respond to COVID-19 vaccination. The study will enroll participants 16 years of age and older, and potential participants can be referred by healthcare providers. All study visits will be conducted in person at the NIH Clinical Center or remotely. Participants can be enrolled before or after vaccination and can have received any of the approved vaccines. 
  • British researchers have reported new data on the transmissibility of the new SARS-CoV-2 variant found in the UK and US. CDC officials have noted that the new variant appears unlikely to impact the effectiveness of the COVID-19 vaccine. The CDC is compiling information about the variants here. 
  • In this excellent opinion article on vaccines and variants, the authors point out several issues related to this problem, including issues with suboptimal immunity limiting the number or increasing the interval between doses, ability of vaccine-induced neutralizing antibodies to attack the virus, the loss of effectiveness of monoclonal antibodies against the variants, and then they propose an approach to the problem. (JAMA, January 28) 
  • This recent article from the Lancet explains why multiple vaccines may be needed across different populations. (November 14, 2020) 
  • ACIP and ACOG recommend that vaccination should not be withheld from pregnant or lactating women, but they should be informed there are insufficient safety data available at this time. AAAAI research partner MotherToBaby has more information on the vaccine in pregnant and lactating women.