This is a summary, written by members of the CITF Secretariat, of:

Tauzin A, Gong SY, Chatterjee D, Ding S, Painter MM, Goel RR, Beaudoin-Bussières G, Marchitto L, Boutin M, Laumaea A, Okeny J, Gendron-Lepage G, Bourassa C, Medjahed H, Goyette G, Williams JC, Bo Y, Gokool L, Morrisseau C, Arlotto P, Bazin R, Fafard J, Tremblay C, Kaufmann DE, De Serres G, Richard J, Côté M, Duerr R, Martel-Laferrière V, Greenplate AR, Wherry EJ, Finzi A. A boost with SARS-CoV-2 BNT162b2 mRNA vaccine elicits strong humoral responses independently of the interval between the first two doses. Cell Rep. 2022 Oct 25;41(4):111554. doi: 10.1016/j.celrep.2022.111554.

The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.

In a study partially funded by the CITF and published in Cell Reports, Drs. Andrés Finzi (Université de Montréal) and Renée Bazin (Héma-Québec) showed that a third vaccine dose elicited strong antibody responses regardless of the interval between the first and second doses. Furthermore, this research group confirmed their previous observations that, unlike the rapid decline seen months after a booster dose in those individuals never infected with SARS-CoV-2, hybrid immunity led to stronger and longer lasting humoral responses.

Researchers conducted a deep dive into the antibody responses induced post dose two and dose three of mRNA vaccines. The scarcity of vaccines at the beginning of nationwide vaccination campaigns led to an increased interval between the first two doses from the manufacturer’s recommendations of three to four weeks to as long as 16 weeks. Early results from this group were the first to show that this increased interval may have led to more mature and robust immune responses (1). However, the relative impact of this early advantage from prolonged interval dosing was unclear in the face of further booster doses.

Key points:

  • Two doses of vaccine induced robust antibody responses against the ancestral, Delta and Omicron variants in both COVID-naïve and previously infected individuals that declined rapidly within four months. However, as early as four weeks after a third dose, antibody responses are restored to previously observed peaks. Those peaks tended to decrease four months later.
  • Individuals with a previous infection had more effective neutralization and antibody-mediated clearance of infected cells compared to COVID-naïve individuals after three doses of vaccine. Analysis of antibody function demonstrated that infection may prime the immune system differently than vaccination.
  • The third dose induced a strong boost in individuals vaccinated with a short interval between dose one and dose two (three to four weeks vs. 16 weeks). This was observable in the overall quantity of anti-RBD IgG antibodies and associated functions such as antibody avidity and antibody-mediated clearance of infected cells.
  • Yet, despite of the strong boost in immune responses in the short interval group, three to four months after dose three, those boosted with a longer interval still demonstrated significantly better neutralization against Omicron BA.4 and BA.5 variants.

1. https://pubmed.ncbi.nlm.nih.gov/34953513/ and https://pubmed.ncbi.nlm.nih.gov/35216664/