Both Pfizer and Moderna had previously run clinical trails on an earlier version (with the BA.1 mRNA component), and based on that data officials were hopeful this updated booster would be an improvement, but due to time constraints testing had not been completed at the time authorization was granted.
We are just now starting to get studies comparing the immunogenicity of this newer bivalent booster to the older monovalent booster, and the first couple suggest that this new bivalent vaccine may not be much of an improvement over the old one.
Both cite immune imprinting from prior antigenic exposure as potential obstacles in creating newer boosters. This is a topic we've explored before (see Science: Heterologous Infection and Vaccination Shapes Immunity Against SARS-CoV-2 Variants).
The first study, out of Israel, was published yesterday in the bioRxiv repository.
Immunogenicity of the BA.5 Bivalent mRNA Vaccine Boosters
Ai-ris Collier, Jessica Miller, Nicole Hachmann, Katherine McMahan, Jinyan Liu, Esther Bondzie, Lydia Gallup, Marjorie Rowe, Eleanor Shonberg, Siline Thai, Julia Barrett, Erica Borducchi, Emily Bouffard, Catherine Jacob-Dolan, Camille Mazurek, Audrey Mutoni, Olivia Powers, Michaela Sciacca, Nehalee Surve, Haley VanWyk, Cindy Wu, Dan Barouch
doi: https://doi.org/10.1101/2022.10.24.513619This article is a preprint and has not been certified by peer review [what does this mean?].
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Abstract
Waning immunity following mRNA vaccination and the emergence of SARS-CoV-2 variants has led to reduced mRNA vaccine efficacy against both symptomatic infection and severe disease. Bivalent mRNA boosters expressing the Omicron BA.5 and ancestral WA1/2020 Spike proteins have been developed and approved, because BA.5 is currently the dominant SARS-CoV-2 variant and substantially evades neutralizing antibodies (NAbs). Our data show that BA.5 NAb titers were comparable following monovalent and bivalent mRNA boosters.
(SNIP)
Our data demonstrate that both monovalent and bivalent mRNA boosters markedly increased antibody responses but did not substantially augment T cell responses. BA.5 NAb titers were comparable following monovalent and bivalent mRNA boosters, with a modest and nonsignificant trend favoring the bivalent booster by a factor of 1.3. These findings are consistent with data recently reported for a BA.1-containing bivalent mRNA booster4.
Our findings suggest that immune imprinting by prior antigenic exposure5 may pose a greater challenge than currently appreciated for inducing robust immunity to SARS-CoV-2 variants.
The second study, which presents similar findings, is not made available under a creative commons license, but can be read at the following link:
Antibody responses to Omicron BA.4/BA.5 bivalent mRNA vaccine booster shot
Qian Wang, Anthony Bowen, Riccardo Valdez, Carmen Gherasim, Aubree Gordon, Liu Lihong, David D Ho
bioRxiv 2022.10.22.513349; doi: https://doi.org/10.1101/2022.10.22.513349
(Excerpt)
"When given as a fourth dose, a bivalent mRNA vaccine targeting Omicron BA.4/BA.5 and an ancestral SARS-CoV-2 strain did not induce superior neutralizing antibody responses in humans, at the time period tested, compared to the original monovalent vaccine formulation."
As with the previous study, the authors suggest `. . . . These findings may be indicative of immunological imprinting . . . " although they state further studies are needed.
While this isn't the home run that the vaccine manufacturers (and the government) were hoping for, these are small, preliminary, laboratory studies and they may not be telling us the full story.We may find these boosters perform better in the real world than these laboratory neutralization findings suggest. Or not.
But at the very least, these new boosters appear to increase titers against BA.5 about well as the old booster shot. With winter approaching, any boost is probably better than no boost at all (full disclosure, I got the bivalent booster last month).
For more on the highly complex (and poorly understood) science of immune imprinting, you may wish to revisit:
Nature Comms: Middle-Aged Individuals May Be in a Perpetual State of H3N2 Flu Virus Susceptibility
Nature: Declan Butler On How Your First Bout Of Flu Leaves A Lasting Impression
