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

Tauzin A, Nicolas A, Ding S, Benlarbi M, Medjahed H, Chatterjee D, Dionne K, Gong SY, Gendron-Lepage G, Bo Y, Perreault J, Goyette G, Gokool L, Arlotto P, Morrisseau C, Tremblay C, Martel-Laferrière V, De Serres G, Levade I, Kaufmann DE, Côté M, Bazin R, Finzi A. Spike recognition and neutralization of SARS-CoV-2 Omicron subvariants elicited after the third dose of mRNA vaccine. Cell Rep. 2023 Jan 31;42(1):111998. doi: 10.1016/j.celrep.2023.111998.

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

A partially CITF-funded study published in Cell Reports demonstrated that people infected with SARS-CoV-2, whether before or after vaccination, have better antibody responses than vaccinated individuals who were never infected (SARS-CoV-2 naïve). This indicates that hybrid immunity generates better immune responses against the ancestral virus, its variants and subvariants. The team also observed that BA.4/5 and BQ.1.1 spike glycoproteins are more resistant to neutralization than other Omicron subvariants, even with three doses of SARS-CoV-2 vaccine. The study was a collaboration between Drs. Andrés Finzi (Université de Montréal) and Renée Bazin (Héma-Québec), along with Dr. Daniel Kaufmann (Université de Montréal).

Forty-five individuals participated in the study. Each had a 16 week interval between their first two doses and received their booster dose seven months later. The cohort included:

  • 15 individuals who were never infected with SARS-CoV-2;
  • 15 individuals who were infected during the first wave of COVID-19 in early 2020 (with the original wild type virus) and prior to vaccination; and
  • 15 individuals who were vaccinated and then infected (breakthrough infection). between mid-December 2021 and May 2022, when Omicron variants (BA.1 and BA.2) were prevailing in Quebec.

Key findings:

  • The level of receptor binding domain (RBD)-specific IgG antibodies significantly decreased in all groups, but more so in SARS-CoV-2 naive individuals. However, four months after the third vaccine dose, the differences in IgG levels observed between those never infected, those with breakthrough infections, and those infected prior to vaccination were not significant. Four months after the third dose, the avidity of interaction between these antibodies and the virus decreased slightly for naïve individuals but remained stable for the those previously infected or those with a breakthrough infection.
  • Four months after the boost, the level of circulating RBD-specific B cells significantly decreased for SARS-CoV-2 naïve donors, but not for individuals with hybrid immunity (individuals with breakthrough infections or those who were infected prior to their vaccination). However, individuals with breakthrough infections actually saw an increase in RBD-specific B cells, noted to be highest in those with recent infections.
  • The ability to recognize and neutralize the wild-type virus and different Omicron subvariant spikes was significantly decreased for SARS-CoV-2 naïve and previously infected individuals. The one exception was with respect to the BQ.1.1 spike, for which the level remained stable among those who had been previously infected. For those with a breakthrough infection, the level of recognition remained more stable than for the other groups and reached the same level as the previously infected group for all the tested spike glycoproteins. Of note, BA.4/5 and the BQ.1.1 spikes were always recognized more poorly than the wild-type and other Omicron subvariant spikes in all groups.
  • Weak or no neutralizing activity was detected against Omicron subvariant spike proteins in most infection naïve individuals. For the individuals who had been previously infected or had a breakthrough infection, although neutralizing activity was higher, the BA.4/5, BA.2.75, BA.4.6, and BQ.1.1 spike proteins were also significantly less neutralized than the wild-type strain and, in some instances, BA.2 spike proteins.