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

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 _RBD ) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHH _MHCII ). 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 _MHCII -Spike _RBD elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHH _MHCII -Spike _RBD is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.
Competing Interests: Competing interest statement: N.P., T.J.H., and H.L.P. have filed a patent with the Boston Children’s Hospital for the use of nanobody conjugates as immunomodulatory vaccines. P.W.R. and S.P.J.W. have filed a patent with Washington University for VSV-SARS-CoV-2 and its variants. S.P.J.W has received unrelated funding support in sponsored research agreements with Vir Biotechnology, AbbVie, and sAB therapeutics.
(Copyright © 2021 the Author(s). Published by PNAS.)