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 K. Alexander, Renate Van den Doel, Mariel J. Liebeskind, Maria A. Vakaki, Nicholas McCaul, Charlotte Wijne, Elisha Verhaar, William Pinney, Hailey Heston, Louis Marie Bloyet, Marjorie Cornejo Pontelli, Ma Xenia G. Ilagan, Robert Jan Lebbink, William J. Buchser, Emmanuel J.H.J. Wiertz, Sean P.J. WhelanHidde L. Ploegh

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


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.

Original languageEnglish
Article numbere2116147118
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number44
Early online date15 Oct 2021
Publication statusPublished - 2 Nov 2021
Externally publishedYes


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