TY - JOUR
T1 - SARS-CoV-2 RBD Neutralizing Antibody Induction is Enhanced by Particulate Vaccination
AU - Huang, Wei Chiao
AU - Zhou, Shiqi
AU - He, Xuedan
AU - Chiem, Kevin
AU - Mabrouk, Moustafa T.
AU - Nissly, Ruth H.
AU - Bird, Ian M.
AU - Strauss, Mike
AU - Sambhara, Suryaprakash
AU - Ortega, Joaquin
AU - Wohlfert, Elizabeth A.
AU - Martinez-Sobrido, Luis
AU - Kuchipudi, Suresh V.
AU - Davidson, Bruce A.
AU - Lovell, Jonathan F.
N1 - Funding Information:
The authors acknowledge assistance from Dr. Michael Farzan and Dr. Huihui Mu for providing the reagents and protocols to generate pseudovirus, as well as providing HEK293 cells expressing hACE2. This study was supported by the National Institutes of Health (R01AI148557 and R01CA247771). The authors thank Kelly Sears and other staff members of the Facility for Electron Microscopy Research (FEMR) at McGill University. FEMR is supported by the Canadian Foundation for Innovation, Quebec Government and McGill University. All animal experiments were carried out in accordance to protocols approved by the University at Buffalo or the Pocono Rabbit Farm Institutional Animal Care and Use Committee.
Funding Information:
The authors acknowledge assistance from Dr. Michael Farzan and Dr. Huihui Mu for providing the reagents and protocols to generate pseudovirus, as well as providing HEK293 cells expressing hACE2. This study was supported by the National Institutes of Health (R01AI148557 and R01CA247771). The authors thank Kelly Sears and other staff members of the Facility for Electron Microscopy Research (FEMR) at McGill University. FEMR is supported by the Canadian Foundation for Innovation, Quebec Government and McGill University. All animal experiments were carried out in accordance to protocols approved by the University at Buffalo or the Pocono Rabbit Farm Institutional Animal Care and Use Committee.
Publisher Copyright:
© 2020 Wiley-VCH GmbH
PY - 2020/12/17
Y1 - 2020/12/17
N2 - The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a candidate vaccine antigen that binds angiotensin-converting enzyme 2 (ACE2), leading to virus entry. Here, it is shown that rapid conversion of recombinant RBD into particulate form via admixing with liposomes containing cobalt-porphyrin-phospholipid (CoPoP) potently enhances the functional antibody response. Antigen binding via His-tag insertion into the CoPoP bilayer results in a serum-stable and conformationally intact display of the RBD on the liposome surface. Compared to other vaccine formulations, immunization using CoPoP liposomes admixed with recombinant RBD induces multiple orders of magnitude higher levels of antibody titers in mice that neutralize pseudovirus cell entry, block RBD interaction with ACE2, and inhibit live virus replication. Enhanced immunogenicity can be accounted for by greater RBD uptake into antigen-presenting cells in particulate form and improved immune cell infiltration in draining lymph nodes. QS-21 inclusion in the liposomes results in an enhanced antigen-specific polyfunctional T cell response. In mice, high dose immunization results in minimal local reactogenicity, is well-tolerated, and does not elevate serum cobalt levels. Taken together, these results confirm that particulate presentation strategies for the RBD immunogen should be considered for inducing strongly neutralizing antibody responses against SARS-CoV-2.
AB - The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is a candidate vaccine antigen that binds angiotensin-converting enzyme 2 (ACE2), leading to virus entry. Here, it is shown that rapid conversion of recombinant RBD into particulate form via admixing with liposomes containing cobalt-porphyrin-phospholipid (CoPoP) potently enhances the functional antibody response. Antigen binding via His-tag insertion into the CoPoP bilayer results in a serum-stable and conformationally intact display of the RBD on the liposome surface. Compared to other vaccine formulations, immunization using CoPoP liposomes admixed with recombinant RBD induces multiple orders of magnitude higher levels of antibody titers in mice that neutralize pseudovirus cell entry, block RBD interaction with ACE2, and inhibit live virus replication. Enhanced immunogenicity can be accounted for by greater RBD uptake into antigen-presenting cells in particulate form and improved immune cell infiltration in draining lymph nodes. QS-21 inclusion in the liposomes results in an enhanced antigen-specific polyfunctional T cell response. In mice, high dose immunization results in minimal local reactogenicity, is well-tolerated, and does not elevate serum cobalt levels. Taken together, these results confirm that particulate presentation strategies for the RBD immunogen should be considered for inducing strongly neutralizing antibody responses against SARS-CoV-2.
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U2 - 10.1002/adma.202005637
DO - 10.1002/adma.202005637
M3 - Article
C2 - 33111375
AN - SCOPUS:85093977503
SN - 0935-9648
VL - 32
JO - Advanced Materials
JF - Advanced Materials
IS - 50
M1 - 2005637
ER -