A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants
Novalia Pishesha, Thibault J. Harmand, Paul W. Rothlauf, Patrique Praest, Ryan Alexander, Renate van den Doel, Mariel J. Liebeskind, Maria A. Vakaki, Nicholas McCaul, Charlotte Wijne, Elisha R. Verhaar, William Pinney, Hailey M. Heston, Louis-Marie Bloyet, Marjorie Cornejo Pontelli, Ma. Xenia G. Ilagan, Robert Jan Lebbink, William Buchser, Emmanuel J. H. J. Wiertz, Sean P. J. Whelan, Hidde L. Ploegh
Abstract
Significance Vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. Currently available vaccines require cold storage and sophisticated manufacturing capacity, complicating their distribution, especially in less developed countries. We report a protein-based SARS-CoV-2 vaccine that directly and specifically targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (Spike RBD ) fused to a nanobody that recognizes class II major histocompatibility complex antigens (VHH MHCII ). Our vaccine elicits robust humoral (high-titer binding and neutralizing antibodies) and cellular immunity against SARS-CoV-2 and its variants in both young and aged mice. VHH MHCII -Spike RBD is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy, desirable attributes for logistical reasons.