A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants.

Pishesha, Novalia; Harmand, Thibault J; Rothlauf, Paul W; Praest, Patrique; Alexander, Ryan K; van den Doel, Renate; Liebeskind, Mariel J; Vakaki, Maria A et al. · Proc Natl Acad Sci U S A · 2021

basic_science · Level V

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Abstract

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 100 million infections and millions of deaths. Effective vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. The vaccines in current use require cold storage and sophisticated manufacturing capacity, which complicates their distribution, especially in less developed countries. We report the development of a candidate SARS-CoV-2 vaccine that is purely protein based and directly targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (Spike<sub>RBD</sub>) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHH<sub>MHCII</sub>). This vaccine elicits robust humoral and cellular immunity against SARS-CoV-2 and its variants. Both young and aged mice immunized with two doses of VHH<sub>MHCII</sub>-Spike<sub>RBD</sub> elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHH<sub>MHCII</sub>-Spike<sub>RBD</sub> is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.

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