TY - JOUR
T1 - A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants
AU - Pishesha, Novalia
AU - Harmand, Thibault J.
AU - Rothlauf, Paul W.
AU - Praest, Patrique
AU - Alexander, Ryan K.
AU - Van den Doel, Renate
AU - Liebeskind, Mariel J.
AU - Vakaki, Maria A.
AU - McCaul, Nicholas
AU - Wijne, Charlotte
AU - Verhaar, Elisha
AU - Pinney, William
AU - Heston, Hailey
AU - Bloyet, Louis Marie
AU - Pontelli, Marjorie Cornejo
AU - Xenia G. Ilagan, Ma
AU - Lebbink, Robert Jan
AU - Buchser, William J.
AU - Wiertz, Emmanuel J.H.J.
AU - Whelan, Sean P.J.
AU - Ploegh, Hidde L.
N1 - Publisher Copyright:
© 2021 National Academy of Sciences. All rights reserved.
PY - 2021/11/2
Y1 - 2021/11/2
N2 - 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.
AB - 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.
KW - COVID-19
KW - Nanobody
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=85118213216&partnerID=8YFLogxK
U2 - 10.1073/pnas.2116147118
DO - 10.1073/pnas.2116147118
M3 - Article
C2 - 34654739
AN - SCOPUS:85118213216
SN - 0027-8424
VL - 118
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 44
M1 - e2116147118
ER -