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  • Writer's pictureFibonacciMD

Second Bivalent COVID Vaccine Booster ... Yes or No?

1) Second Bivalent Covid Vaccine Booster Recommendations

2) Is the Bivalent a Better Vaccine?

3) How Much Protection Does a Previous Covid Infection Confer?

In Brief

The FDA has authorized a second dose of the bivalent (original and omicron BA.4/BA.5 strains) COVID booster for individuals 65 years of age and older at least four months following their initial bivalent dose.

Most immunocompromised individuals who have received a bivalent COVID-19 vaccine may receive a single additional dose of a bivalent COVID-19 vaccine at least 2 months following a dose of a bivalent COVID-19 vaccine, and additional doses may be administered at the discretion of, and at intervals determined by, their healthcare provider. There are different eligibility requirements for immunocompromised individuals 6 months through 4 years of age based on initial vaccine. However, a more complete recommendation had not yet been released when this article was written.[1,2]

A second bivalent booster vaccination is not recommended for any other age group at this time.[1]

The FDA states that a second bivalent dose for individuals 65 years of age and older is supported by data showing the waning of immunity in this population over time and its restoration by an additional dose. Based on evidence from studies conducted previously, immunocompromised individuals may also require additional doses to maintain immunity.[1]

How long does protection from the bivalent vaccine last?

A study published in January 2023 found that protection against symptomatic infection lasted at least 3 months after bivalent vaccination in non-immunocompromised individuals who had received at least one dose of monovalent vaccine previously. Vaccine efficacy (VE) against symptomatic omicron BA.5-related infection after 3 months was 52% in persons aged 18–49 years, 43% in persons aged 50–64, and 37% among those aged ≥65 years. VE against symptomatic XBB/XBB.1.5-related infection was 49% among persons aged 18–49, 40% among persons aged 50–64 years, and 43% among those aged ≥65 years. Evidence of waning VE by 2–3 months after receiving a bivalent dose was minimal. The study did not look at the rate of serious infection prevention. [3]

Is the bivalent vaccine better than the older monovalent vaccine?

There is data that the efficacy of the bivalent vaccine which contains both spike protein antigens used in the original vaccine and the BA.4/BA.5 strains, is no better at preventing disease than the original monovalent RNA vaccine (which is no longer available).[4,5] One study tested subjects who never had a covid infection with a different bivalent mixture of B.1 omicron virus and original virus and found a 1.9% infection rate in the monovalent vaccine group compared to 3.2% in the bivalent vaccine group.[6] This vaccine was not the one chosen to be manufactured and distributed. However, this information, which was available at the time, was not disclosed to the FDA’s advisory committee before they initially approved the emergency authorization for the bivalent vaccine. Although this information might not have had any effect on the final decision, this lack of disclosure, according to a news report, made some of the advisors on the committee angry and disappointed when they found out.[7]

It is felt that the lack of improved efficacy of the bivalent vaccine over the older monovalent vaccine might be due to immune imprinting.[8,9] Immune imprinting is where initial exposure to one virus strain primes B cell memory and limits the development of new memory B cells and neutralizing antibodies against variant strains of the virus. Thus, antibodies that work against both the newer and ancestral viral strains are produced without producing specific antibodies unique to the newer strains.[9] It has been theorized that the protection from COVID infection might have been improved if the newer vaccine was monovalent, with only the newer strains included, or had been formulated with larger amounts of the newer strains rather than the current bivalent vaccine formulation.[8]

How much protection does a previous COVID infection confer?

A systematic review and meta-analysis of how long antibody protection remains after a COVID infection found that protection from re-infection from the original virus, alpha, and delta variants declined over time but remained at 78.6% at 40 weeks and 55.5% at 80 weeks. Protection against re-infection by the omicron BA.1 variant declined more rapidly and was estimated at 36.1% at 40 weeks. Two studies in the meta-analysis looked at protection from re-infection after omicron BA.2 infection and found it was 85.4% at 4 weeks and 37% at 40 weeks.

Protection against severe disease was high for all variants, with 90.2% for original virus , alpha, and delta variants, and 88.9% for omicron BA.1 at 40 weeks.

The authors concluded that protection from past infection wanes over time, but the level of protection against re-infection, symptomatic disease, and severe disease appears to be at least as durable, if not more so, than that provided by two-dose vaccination with the mRNA vaccines for the original virus, alpha, delta, and omicron BA.1 variants. [10]


The FDA has recommended that a Spring 2023 COVID bivalent booster may be given to individuals over 65 years of age at least 4 months after their last vaccination or those who are immunocompromised at least 2 months after their last vaccine after consultation with their providers.

The bivalent COVID vaccine, while boosting immunity, does not appear to be any more effective than the original monovalent vaccines at preventing illness. This may be due to immune imprinting.

A previous COVID infection does induce some long-term immunity from severe disease, the length of which may vary by the COVID strain causing the infection.


[1] Coronavirus (COVID-19) Update: FDA Authorizes Changes to Simplify Use of Bivalent mRNA COVID-19 Vaccines. FDA. 04/18/2023. Retrieved from: fda-authorizes-changes-simplify-use-bivalent-mrna-covid-19-vaccines [2] Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States. CDC. last updated April 22, 2023. Retrieved from: us.html [3] Link-Gelles R, Ciesla AA, Roper LE, et al. Early Estimates of Bivalent mRNA Booster Dose Vaccine Effectiveness in Preventing Symptomatic SARS-CoV-2 Infection Attributable to Omicron BA.5– and XBB/XBB.1.5–Related Sublineages Among Immunocompetent Adults — Increasing Community Access to Testing Program, United 3

States, December 2022–January 2023. MMWR Morb Mortal Wkly Rep 2023;72:119–124. Retrieved from: [4] Wang Q et al. Antibody responses to Omicron BA.4/BA.5 bivalent mRNA vaccine booster shot. bioRxiv 2022. October 24,2022. Retrieved from: [5] Collier AY et al. Immunogenicity of BA.5 Bivalent mRNA Vaccine Boosters. N Engl J Med 2023; 388:565-567. February 9, 2023. Retrieved from: [6] Chalkias S et al. A Bivalent Omicron-Containing Booster Vaccine against Covid-19. N Engl J Med 2022; 387:1279-1291. Retrieved from: [7] Cohen E, Thomas N. FDA vaccine advisers ‘disappointed’ and ‘angry’ that early data about new Covid-19 booster shot wasn’t presented for review last year. CNN. Retrieved from: transparency/index.html [8] Offit PA. Bivalent Covid-19 Vaccines — A Cautionary Tale. NEJM. February 9, 2023. 388:481-483. Retrieved from: [10] Wheatley AK, Fox A, Tan HX, et al. Immune imprinting and SARS-CoV-2 vaccine design. Trends Immunol. 2021;42(11):956-959. Retrieved from: [9] COVID-19 Forecasting Team. Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis. Volume 401, ISSUE 10379, P833-842, March 11, 2023, Retrieved from:


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