SARS-CoV-2 RBD Neutralizing Antibody Induction is Enhanced by Particulate Vaccination

Wei Chiao Huang, Shiqi Zhou, Xuedan He, Kevin Chiem, Moustafa T. Mabrouk, Ruth H. Nissly, Ian M. Bird, Mike Strauss, Suryaprakash Sambhara, Joaquin Ortega, Elizabeth A. Wohlfert, Luis Martinez-Sobrido, Suresh V. Kuchipudi, Bruce A. Davidson, Jonathan F. Lovell

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


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.

Original languageEnglish (US)
Article number2005637
JournalAdvanced Materials
Issue number50
StatePublished - Dec 17 2020

All Science Journal Classification (ASJC) codes

  • General Materials Science
  • Mechanics of Materials
  • Mechanical Engineering


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