"‘The expectation that Covid-19 vaccines would prevent acquisition of infection and block onward transmission was based on initial data in 2020 (before the emergence of viral variants) that showed high neutralizing antibody titers and robust protective efficacy at peak immunity after mRNA vaccination. However, given the substantial waning of serum neutralizing antibody titers and the emergence of variants with increased transmissibility and antibody escape, it would be reasonable now to recalibrate goals for Covid-19 vaccines. Current vaccines may not provide high-level, sustained protection against infection or transmission with omicron, even after multiple boosts and also after the introduction of updated omicron-specific vaccines. Instead, the most important goal of Covid-19 vaccination should be to provide long-term protection against severe disease, hospitalization, and death from current and future variants.
Booster recommendations should therefore take into account not only peak neutralizing antibody titers but also durable prevention of severe Covid-19 disease. Such protection will probably require a combination of humoral and cellular immunity, with an emphasis on long-term rather than short-term immune responses. However, to date, the field has focused largely on short-term neutralizing antibody responses. The potential role of an omicron-containing booster is currently being explored, but a study in nonhuman primates showed that an omicron-specific mRNA vaccine was not better than the original mRNA-1273 vaccine for protection against omicron challenge.83 Early clinical studies have shown that boosting with bivalent mRNA vaccines containing both ancestral and omicron BA.1 spike immunogens induced peak omicron neutralizing antibody titers that were less than twice the peak titers induced by boosting with the original mRNA vaccines. Thus, clinical benefits of the updated boosters as compared with the current vaccines are not clear. "
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