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Review 1: "XBB.1.5 Monovalent mRNA Vaccine Booster Elicits Robust Neutralizing Antibodies against Emerging SARS-CoV-2 Variants"

The reviewer finds the study's conclusion of widespread administration of XBB.1.5 MV to be valid and strongly supported by the data.

Published onJun 30, 2024
Review 1: "XBB.1.5 Monovalent mRNA Vaccine Booster Elicits Robust Neutralizing Antibodies against Emerging SARS-CoV-2 Variants"

RR:C19 Evidence Scale rating by reviewer:

  • Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.


Review: The study reports that the recently updated COVID mRNA vaccines based on the XBB1.5 spike generate high titers of neutralizing antibody that cross-reacts on several of the other currently circulating variants. These findings suggest that the updated vaccine is better than the previous version and should replace it.

The COVID-19 mRNA vaccines were made possible by the confluence of advances in academic research and the production capacity of industry. They have saved the lives of millions and decreased the suffering of millions more word-wide. In spite of these successes, vaccine effectiveness has been continually challenged by the speed with which the virus is evolving whereby viral spike protein variants are selected for their ability to evade vaccine and infection-elicited antibodies. In this report, investigators from the Columbia University College of Physicians and Surgeons and University of Michigan collaborated to evaluate the effectiveness of newly formulated monovalent mRNA vaccines encoding the XBB1.5 variant spike protein. They find that the updated vaccines increase titers against XBB1.5 by about 27-fold and by nearly as much against the other currently circulating variant spikes. The titers were even higher in individuals previously infected by an omicron subvariant. Furthermore, the updated vaccine, which is monovalent, was better than the earlier bivalent vaccine which was a mix of the earlier D614G and BA.5 spikes, as a result of decreased “immunological imprinting”, a phenomenon in which the immune system stays focused on epitopes in the earlier variant and thus doesn’t respond as well to epitopes in the newer variant. The study was done by measuring neutralizing antibody titers in carefully curated cohorts of individuals of known vaccination and infection status. All were previously vaccinated with wild-type monovalent vaccine and the BA.5 bivalent vaccine and had been infected either by XBB or by an earlier Omicron subvariant. Neutralizing titers were determined using a panel of pseudoviruses with each of the current spike protein variants, a method that provides accurate data. The experimental schemes and results are clearly presented in the figures and the data are statistically significant. The authors conclude that switching to the updated monovalent XBB vaccine is warranted, a conclusion that is firmly supported by the data. A concern is that this could force the virus to evolve yet new escape variants, although at some point, the virus may just run out of new ideas.

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