This evidence review was compiled by members of the CITF Secretariat with the input from experts affiliated with the CITF and does not necessarily reflect the views of all CITF members.

By Mariana Bego

Rising COVID-19 cases spurred by the highly transmissible Delta variant have led policymakers and researchers to consider the need for vaccine booster doses. The goals: reduce the number of COVID-19 cases and enhance immunity in vaccinated people. Although tempting, these decisions should be evidence-based and consider the benefits and risks for individuals and society as a whole. Recent publications and recommendations are described and discussed.

 COVID-19 vaccines continue to be effective against severe disease, including disease caused by the Delta variant. However, additional vaccine doses have been a recent topic of discussion, whether a third dose or a booster dose, depending on the reason for giving it.

  • A third dose would be an additional dose given to moderately to severely immunocompromised people because two doses fail to illicit an expected immune response. This could be required 28 days after the second dose.
  • A booster dose would be an additional dose given to someone who built enough protection after vaccination, but whose protection may have waned (lessened) over time, perhaps 6-8 months following the completion of the initial regime.

Decisions regarding whether to administer additional vaccine doses need to consider the most recent and reliable data and weigh the risk of infection/disease severity in the vaccinated population vs. the benefits of getting more doses to previously unvaccinated populations.1

Key discussion points:

  • A third dose of the COVID-19 vaccine could be appropriate for some individuals in whom the primary vaccination regime might not have induced adequate protection—e.g., immunocompromised individuals. It should be noted, however, that people who did not respond robustly to the primary vaccination regime might still not respond well after three doses given the short time interval between doses.1
  • Boosting might be needed in the general population if immunity to the primary vaccination decreases over time (e.g., immunity waning) or if circulating variants escape immune responses to the original vaccines and they no longer offer adequate protection.1
  • A booster dose of Pfizer–BioNTech’s Comirnaty vaccine given approximately eight months after the initial two-dose regimen given 21 days apart was proven to be safe and effective.2
  • This scheme was also proven effective in a study conducted in Israel. There, a booster dose of Comirnaty given at least five months after the original two doses conferred significant protection to individuals 60 years or older from COVID-19 infection and severe illness, when compared to individuals who only received two doses.3
  • Finally, a single dose of Moderna’s “mRNA vaccine cocktail” (the company made a vaccine specifically designed for multiple variants), given as booster was shown to be safe and effective in a preliminary report from an ongoing trial.4

It was proposed that using a booster dose specifically made to fight the circulating variants could be the best alternative, rather than giving a booster using the original vaccines, which were designed for the original strain of SARS-CoV-2. This strategy would be similar to the one used for influenza vaccines and increases the likelihood that the booster will remain effective despite further virus evolution. 4

Third vaccine doses have already been made available in several provinces to the immunocompromised and to some Canadians in long-term care. A recent study, by CITF-funded researcher Dr. Deepali Kumar and collaborators from University Health Network in Toronto, shows that a third vaccine dose was safe and very effective at increasing antibody levels in organ transplant recipients. Canada’s National Advisory Committee on Immunization (NACI) recently recommended that third doses given to moderately to severely immunocompromised individuals. NACI is also currently weighing the available data on the benefits of booster shots to the general population, and is expected to issue guidance soon.



1- Krause PR, Fleming TR, Peto R, Longini IM, Figueroa JP, Sterne JAC, Cravioto A, Rees H, Higgins JPT, Boutron I, Pan H, Gruber MF, Arora N, Kazi F, Gaspar R, Swaminathan S, Ryan MJ, Henao-Restrepo AM. Considerations in boosting COVID-19 vaccine immune responses. Lancet. 13 Sept 2021. DOI:10.1016/S0140-6736(21)02046-8

2- Falsey AR, Frenck RW Jr, Walsh EE, Kitchin N, Absalon J, Gurtman A, Lockhart S, Bailey R, Swanson KA, Xu X, Koury K, Kalina W, Cooper D, Zou J, Xie X, Xia H, Türeci Ö, Lagkadinou E, Tompkins KR, Shi PY, Jansen KU, Şahin U, Dormitzer PR, Gruber WC. SARS-CoV-2 Neutralization with BNT162b2 Vaccine Dose 3. N Engl J Med. 15 Sept 2021. DOI: 10.1056/NEJMc2113468

3- Bar-On YM, Goldberg Y, Mandel M, Bodenheimer O, Freedman L, Kalkstein N, Mizrahi B, Alroy-Preis S, Ash N, Milo R, Huppert A. Protection of BNT162b2 Vaccine Booster against Covid-19 in Israel. N Engl J Med. 15 Sept 2021. doi: 10.1056/NEJMoa2114255.

4- Choi A, Koch M, Wu K, Chu L, Ma L, Hill A, Nunna N, Huang W, Oestreicher J, Colpitts T, Bennett H, Legault H, Paila Y, Nestorova B, Ding B, Montefiori D, Pajon R, Miller JM, Leav B, Carfi A, McPhee R, Edwards DK. Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis. Nat Med. 15 Sept 2021. DOI: 10.1038/s41591-021-01527-y