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

Abstract

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.

Engineering a self-navigated MnARK nanovaccine for inducing potent protective immunity against novel coronavirus

“…RBD can be fully exposed during the binding process between novel coronavirus and host cells and is readily recognized by the host immune system to produce immune responses [25] . Multiple recent reports have also supported the critical role of RBD in inducing anti- novel coronavirus neutralizing antibodies in various animal models and humans [26] , [27] , [28] . In the current study, we selected the RBD (amino acid residues 319-541) of the novel coronavirus spike protein as the vaccine antigen.…”

Induction of Potent and Durable Neutralizing Antibodies Against SARS-CoV-2 Using a Receptor Binding Domain-Based Immunogen

“…Compared to monomeric RBD which only induced NT 50 of only 128 or 256 in two of eight animals, dimeric RBD induced average NT 50 of 3,008. Another strategy that has been evaluated is to deliver RBD as a particulate form using liposomes ( 54 ). Here, a recombinant RBD with a histidine tag was incorporated onto liposomes containing cobalt-porphyrin-phospholipid (CoPoP).…”

Mechanism of a COVID-19 nanoparticle vaccine candidate that elicits a broadly neutralizing antibody response to SARS-CoV-2 variants

“…Superior NAb responses have been reported for other COVID-19 vaccine candidates that take advantage of particulate display (66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78). Importantly, our S2GΔHR2-presenting I3-01v9 SApNP vaccine elicited bNAb responses to three SARS-CoV-2 VOCs (Fig.…”