A Recombinant Protein XBB.1.5 RBD/Alum/CpG Vaccine Elicits High Neutralizing Antibody Titers against Omicron Subvariants of SARS-CoV-2

Authors

Syamala Rani Thimmiraju
Rakesh Adhikari
Maria Jose Villar
Jungsoon Lee
Zhuyun Liu
Rakhi Kundu
Yi-Lin Chen
Suman Sharma
Karm Ghei
Brian Keegan
Leroy Versteeg
Portia M Gillespie
Allan Ciciriello
Nelufa Y Islam
Cristina Poveda
Nestor Uzcategui
Wen-Hsiang Chen
Jason T Kimata
Bin Zhan
Ulrich Strych
Maria Elena Bottazzi
Peter J Hotez
Jeroen Pollet

Publication Date

10-1-2023

Journal

Vaccines

DOI

10.3390/vaccines11101557

PMID

37896960

PMCID

PMC10610638

PubMedCentral® Posted Date

10-1-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

immune escape, vaccine efficacy, COVID-19, SARS-CoV-2

Abstract

(1) Background: We previously reported the development of a recombinant protein SARS-CoV-2 vaccine, consisting of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, adjuvanted with aluminum hydroxide (alum) and CpG oligonucleotides. In mice and non-human primates, our wild-type (WT) RBD vaccine induced high neutralizing antibody titers against the WT isolate of the virus, and, with partners in India and Indonesia, it was later developed into two closely resembling human vaccines, Corbevax and Indovac. Here, we describe the development and characterization of a next-generation vaccine adapted to the recently emerging XBB variants of SARS-CoV-2. (2) Methods: We conducted preclinical studies in mice using a novel yeast-produced SARS-CoV-2 XBB.1.5 RBD subunit vaccine candidate formulated with alum and CpG. We examined the neutralization profile of sera obtained from mice vaccinated twice intramuscularly at a 21-day interval with the XBB.1.5-based RBD vaccine, against WT, Beta, Delta, BA.4, BQ.1.1, BA.2.75.2, XBB.1.16, XBB.1.5, and EG.5.1 SARS-CoV-2 pseudoviruses. (3) Results: The XBB.1.5 RBD/CpG/alum vaccine elicited a robust antibody response in mice. Furthermore, the serum from vaccinated mice demonstrated potent neutralization against the XBB.1.5 pseudovirus as well as several other Omicron pseudoviruses. However, regardless of the high antibody cross-reactivity with ELISA, the anti-XBB.1.5 RBD antigen serum showed low neutralizing titers against the WT and Delta virus variants. (4) Conclusions: Whereas we observed modest cross-neutralization against Omicron subvariants with the sera from mice vaccinated with the WT RBD/CpG/Alum vaccine or with the BA.4/5-based vaccine, the sera raised against the XBB.1.5 RBD showed robust cross-neutralization. These findings underscore the imminent opportunity for an updated vaccine formulation utilizing the XBB.1.5 RBD antigen.