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Influenza imprinting may push the immune response toward conserved regions of currently circulating influenza virus strains, rather than toward the most immunogenic region of the dominant strain of future influenza epidemics. Similar concerns have been raised for SARS-CoV-2, in particular, whether prior vaccination or infection with pre-omicron variants could alter responses against currently circulating strains. Did we commit an original sin by vaccinating with the spike protein of a now outdated variant of SARS-CoV-2, which will now delay our immune response to future variants and vaccines, leading to higher morbidity and mortality? In other words, is this a scenario to be overcome, as Hoffmann and his colleagues
conclude in their recent correspondence in The Lancet Infectious Diseases?
Infections with omicron variants did not shift the immune response to effectively neutralize novel omicron variants, such as BA.2.75.2 and BQ.1.1, while maintaining high titers against SARS- Wild-type CoV-2.
Maintaining strong titers is despite all omicron variants sharing only a small minority of neutralizing B cell epitopes unchanged with the first SARS-CoV-2 variant.
Whether this broadening of the immune response provides enhanced long-term protection against infection, particularly by emerging omicron variants, remains to be seen.
potentially aided by maintained T cell immunity. And priming with pre-omicron variants of SARS-CoV-2, before infection with early omicron variants BA.1 or BA.2, reduced the risk of reinfection, rather than promoting it.
it appears to be a beneficial population strategy for maintaining high memory B cell immunity against ancestral strains. The action of immune imprinting, by maintaining high neutralizing antibody titers against ancestral strains of SARS-CoV-2 in the population, could help eradicate ancestral strains, in favor of attenuated strains circulating in consecutive waves. A new (hypothetical) strain derived from the delta variant that shares the predisposition to cause lethal outcomes could be the worst case scenario in the future in the pandemic in regions with high population immunity. And immune fingerprinting could help protect us from that prospect.
which exposes the immune system to a wider range of non-neutralizing epitopes. The frequency of vaccinations and the time intervals between them also play an important role. Alternative strategies, such as mucosal vaccines, could also help broaden the immune response.
In the meantime, it should be considered that immune fingerprinting could offer a protective wall against even more serious variants derived from ancestral strains.
SC reports serving on a BioNTech Clinical Advisory Board in 2020. Both SH and SC received study support from Roche Diagnostics.
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Posted: January 30, 2023
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