A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants.
Novalia PisheshaThibault J HarmandPaul W RothlaufPatrique PraestRyan K AlexanderRenate van den DoelMariel J LiebeskindMaria A VakakiNicholas McCaulCharlotte WijneElisha VerhaarWilliam PinneyHailey HestonLouis-Marie BloyetMarjorie Cornejo PontelliMa Xenia G IlaganRobert Jan LebbinkWilliam J BuchserEmmanuel J H J WiertzSean P J WhelanHidde L PloeghPublished in: Proceedings of the National Academy of Sciences of the United States of America (2021)
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 (SpikeRBD) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHHMHCII). 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 VHHMHCII-SpikeRBD elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHHMHCII-SpikeRBD is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.