FDA Expands EUA for Third Dose of Pfizer-BioNTech and Moderna mRNA COVID-19 Vaccines in Immunocompromised Individuals

Today, the U.S. FDA announced the expansion of the Emergency Use Authorization (EUA) for the mRNA COVID-19 vaccine BNT162b2, jointly developed by Pfizer and BioNTech, and the COVID-19 vaccine developed by Moderna, to allow a third booster dose for specific immunocompromised populations, including patients who have received solid organ transplants and those with similarly compromised immune function due to disease. According to estimates by the U.S. Centers for Disease Control and Prevention (CDC), approximately 9 million people in the United States are immunocompromised. A study by Johns Hopkins University found that “immunocompromised individuals are 485 times more likely to be hospitalized or die from COVID-19 compared to the vaccinated general population.”

Currently, the SARS-CoV-2 Delta variant (B.1.617.2), initially identified in India, has spread widely across the globe and has emerged as the predominant circulating variant in numerous countries, raising significant public concern. Notably, breakthrough infections with the Delta variant have been documented among individuals who have already received COVID-19 vaccines. Consequently, whether vaccinated individuals require a third booster dose, along with the optimal timing for its administration, has become a topic of intense public interest.

According to publicly available information from Pfizer, against the widely concerned Delta variant, neutralizing antibody titers increased by more than 5-fold in adults aged 18–55 and by more than 11-fold in older adults aged 65–80 following administration of a third dose of BNT162b2. Furthermore, the third dose demonstrated a tolerability profile consistent with prior doses and a favorable safety profile.

According to recent data released by Moderna, results from a Phase 2 clinical trial evaluating the efficacy of a third booster dose showed that six months after administration of the second dose, neutralizing antibody levels against wild-type SARS-CoV-2 remained at high levels, while levels against the Beta (B.1.351), Gamma (P.1), and Delta variants were significantly reduced. However, following administration of a single 50 μg dose of the mRNA-1273 booster vaccine, neutralizing antibody levels against multiple major SARS-CoV-2 variants of concern increased substantially, with the geometric mean titer (GMT) against the Beta variant rising 32-fold, against Gamma by 43.6-fold, and against Delta by 42.3-fold.

Similarly, AstraZeneca recently published findings on *The Lancet* preprint server regarding the effects of a third dose of the adenovirus vector COVID-19 vaccine Vaxzevria (formerly known as AZD1222). The results showed that administering a third dose at least six months after the second dose of Vaxzevria can increase antibody levels against the SARS-CoV-2 spike protein sixfold. Researchers also evaluated the neutralizing capacity of serum from vaccinated individuals against the Alpha, Beta, and Delta variants, finding that the third dose enhanced neutralizing activity against all three viral strains.

It is worth noting that the immune response elicited by a vaccine in the human body is a complex process that encompasses not only the production of neutralizing antibodies but also virus-specific T-cell responses. Furthermore, memory B cells generated following vaccination can rapidly produce antibodies upon viral re-exposure, which helps alleviate symptoms in patients. Existing research indicates that these memory B cells may persist in the human body for extended periods and further optimize the antibodies produced. Therefore, protective immunity against SARS-CoV-2 in the human body is not limited to neutralizing antibody titers alone.

Recently, the FDA and CDC issued a statement noting that whether a third vaccine dose is necessary and when it should be administered will ultimately be determined through scientific analysis based on multiple data sources, including laboratory and clinical trial data. The FDA’s recent expansion of the Emergency Use Authorization (EUA) for a third booster dose of the Pfizer/BioNTech and Moderna COVID-19 vaccines also demonstrates that the booster dose can provide meaningful support in controlling the pandemic in terms of both efficacy and safety.

We also look forward to the Emergency Use Authorization of the third booster dose, which will provide people with enhanced protection!

References:

[1] Coronavirus (COVID-19) Update: FDA Authorizes Additional Vaccine Dose for Certain Immunocompromised Individuals. Retrieved August 12, 2021, from https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromised

[2]FDA Set to Greenlight Boosters for Some Vulnerable Patients. Retrieved August 13, 2021, https://www.biospace.com/article/fda-expected-to-greenlight-booster-for-pfizer-moderna-vaccines/

[3]Second Quarter 2021 Earnings Teleconference. Retrieved July 28, 2021, from https://s21.q4cdn.com/317678438/files/doc_financials/2021/q2/Q2-2021-Earnings-Charts-FINAL.pdf

[4]Moderna Business Updates First Quarter 2021 Financial Results. Retrieved May 6, 2021, from https://investors.modernatx.com/static-files/c3674f1b-39d4-4bc5-83a7-904133512154

[5]Flaxman et al., (2021). Tolerability and Immunogenicity After a LateSecond Dose or a Third Dose of ChAdOx1 nCoV-19 (AZD1222).http://dx.doi.org/10.2139/ssrn.3873839