[HTML][HTML] The case for S2: the potential benefits of the S2 subunit of the SARS-CoV-2 spike protein as an immunogen in fighting the COVID-19 pandemic

P Shah, GA Canziani, EP Carter, I Chaiken - Frontiers in immunology, 2021 - frontiersin.org
P Shah, GA Canziani, EP Carter, I Chaiken
Frontiers in immunology, 2021frontiersin.org
As COVID-19 cases continue to rise, it is imperative to learn more about antibodies and T-
cells produced against the causative virus, SARS-CoV-2, in order to guide the rapid
development of therapies and vaccines. While much of the current antibody and vaccine
research focuses on the receptor-binding domain of S1, a less-recognized opportunity is to
harness the potential benefits of the more conserved S2 subunit. Similarities between the
spike proteins of both SARS-CoV-2 and HIV-1 warrant exploring S2. Possible benefits of …
As COVID-19 cases continue to rise, it is imperative to learn more about antibodies and T-cells produced against the causative virus, SARS-CoV-2, in order to guide the rapid development of therapies and vaccines. While much of the current antibody and vaccine research focuses on the receptor-binding domain of S1, a less-recognized opportunity is to harness the potential benefits of the more conserved S2 subunit. Similarities between the spike proteins of both SARS-CoV-2 and HIV-1 warrant exploring S2. Possible benefits of employing S2 in therapies and vaccines include the structural conservation of S2, extant cross-reactive neutralizing antibodies in populations (due to prior exposure to common cold coronaviruses), the steric neutralization potential of antibodies against S2, and the stronger memory B-cell and T-cell responses. More research is necessary on the effect of glycans on the accessibility and stability of S2, SARS-CoV-2 mutants that may affect infectivity, the neutralization potential of antibodies produced by memory B-cells, cross-reactive T-cell responses, antibody-dependent enhancement, and antigen competition. This perspective aims to highlight the evidence for the potential advantages of using S2 as a target of therapy or vaccine design.
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