tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2021 Nov 2;118(44):e2116147118.
doi: 10.1073/pnas.2116147118.
A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants
Novalia Pishesha[SUP] 1 2 3 4 [/SUP], Thibault J Harmand[SUP] 2 [/SUP], Paul W Rothlauf[SUP] 5 6 [/SUP], Patrique Praest[SUP] 7 [/SUP], Ryan K Alexander[SUP] 2 [/SUP], Renate van den Doel[SUP] 2 [/SUP], Mariel J Liebeskind[SUP] 8 [/SUP], Maria A Vakaki[SUP] 8 [/SUP], Nicholas McCaul[SUP] 2 [/SUP], Charlotte Wijne[SUP] 2 [/SUP], Elisha Verhaar[SUP] 2 [/SUP], William Pinney 3rd[SUP] 2 [/SUP], Hailey Heston[SUP] 2 [/SUP], Louis-Marie Bloyet[SUP] 5 [/SUP], Marjorie Cornejo Pontelli[SUP] 5 [/SUP], Ma Xenia G Ilagan[SUP] 9 10 [/SUP], Robert Jan Lebbink[SUP] 7 [/SUP], William J Buchser[SUP] 8 [/SUP], Emmanuel J H J Wiertz[SUP] 7 [/SUP], Sean P J Whelan[SUP] 5 [/SUP], Hidde L Ploegh[SUP] 11 [/SUP]
Affiliations
Abstract
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[SUB]RBD[/SUB]) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHH[SUB]MHCII[/SUB]). 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[SUB]MHCII[/SUB]-Spike[SUB]RBD[/SUB] elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHH[SUB]MHCII[/SUB]-Spike[SUB]RBD[/SUB] is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.
. 2021 Nov 2;118(44):e2116147118.
doi: 10.1073/pnas.2116147118.
A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants
Novalia Pishesha[SUP] 1 2 3 4 [/SUP], Thibault J Harmand[SUP] 2 [/SUP], Paul W Rothlauf[SUP] 5 6 [/SUP], Patrique Praest[SUP] 7 [/SUP], Ryan K Alexander[SUP] 2 [/SUP], Renate van den Doel[SUP] 2 [/SUP], Mariel J Liebeskind[SUP] 8 [/SUP], Maria A Vakaki[SUP] 8 [/SUP], Nicholas McCaul[SUP] 2 [/SUP], Charlotte Wijne[SUP] 2 [/SUP], Elisha Verhaar[SUP] 2 [/SUP], William Pinney 3rd[SUP] 2 [/SUP], Hailey Heston[SUP] 2 [/SUP], Louis-Marie Bloyet[SUP] 5 [/SUP], Marjorie Cornejo Pontelli[SUP] 5 [/SUP], Ma Xenia G Ilagan[SUP] 9 10 [/SUP], Robert Jan Lebbink[SUP] 7 [/SUP], William J Buchser[SUP] 8 [/SUP], Emmanuel J H J Wiertz[SUP] 7 [/SUP], Sean P J Whelan[SUP] 5 [/SUP], Hidde L Ploegh[SUP] 11 [/SUP]
Affiliations
- PMID: 34654739
- DOI: 10.1073/pnas.2116147118
Abstract
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[SUB]RBD[/SUB]) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHH[SUB]MHCII[/SUB]). 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[SUB]MHCII[/SUB]-Spike[SUB]RBD[/SUB] elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHH[SUB]MHCII[/SUB]-Spike[SUB]RBD[/SUB] is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.