A Recombinant Protein XBB.1.5 RBD/Alum/CpG Vaccine Elicits High Neutralizing Antibody Titers against Omicron Subvariants of SARS-CoV-2
Author:
Thimmiraju Syamala Rani12, Adhikari Rakesh12, Villar Maria Jose12, Lee Jungsoon12, Liu Zhuyun12, Kundu Rakhi12, Chen Yi-Lin12, Sharma Suman3, Ghei Karm3, Keegan Brian12, Versteeg Leroy12ORCID, Gillespie Portia M.12ORCID, Ciciriello Allan12, Islam Nelufa Y.12, Poveda Cristina12, Uzcategui Nestor12, Chen Wen-Hsiang12, Kimata Jason T.3ORCID, Zhan Bin12ORCID, Strych Ulrich12ORCID, Bottazzi Maria Elena1245ORCID, Hotez Peter J.1245, Pollet Jeroen12ORCID
Affiliation:
1. Texas Children’s Hospital Center for Vaccine Development, Houston, TX 77030, USA 2. Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA 3. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA 4. Department of Biology, Baylor University, Waco, TX 76706, USA 5. James A. Baker III Institute for Public Policy, Rice University, Houston, TX 77005, USA
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.
Funder
Robert J. Kleberg Jr. and Helen C. Kleberg Foundation Fifth Generation, Inc. JPB Foundation Texas Children’s Hospital Center for Vaccine Development Intramural Funds
Subject
Pharmacology (medical),Infectious Diseases,Drug Discovery,Pharmacology,Immunology
Reference25 articles.
1. SARS-CoV-2 variant biology: Immune escape, transmission and fitness;Carabelli;Nat. Rev. Microbiol.,2023 2. SARS-CoV-2 variant omicron XBB.1.5: Challenges and prospects–correspondence;Channabasappa;Int. J. Surg.,2023 3. Gerardi, V., Rohaim, M.A., Naggar, R.F.E., Atasoy, M.O., and Munir, M. (2023). Deep Structural Analysis of Myriads of Omicron Sub-Variants Revealed Hotspot for Vaccine Escape Immunity. Vaccines, 11. 4. Enhanced evasion of neutralizing antibody response by Omicron XBB.1.5, CH.1.1, and CA.3.1 variants;Qu;Cell. Rep.,2023 5. A recombinant spike-XBB.1.5 protein vaccine induces broad-spectrum immune responses against XBB.1.5-included Omicron variants of SARS-CoV-2;He;MedComm,2023
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|