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

Version 1 : Received: 1 September 2023 / Approved: 4 September 2023 / Online: 5 September 2023 (03:47:28 CEST)
Version 2 : Received: 5 September 2023 / Approved: 6 September 2023 / Online: 7 September 2023 (10:17:31 CEST)
Version 3 : Received: 12 September 2023 / Approved: 13 September 2023 / Online: 13 September 2023 (07:35:34 CEST)
Version 4 : Received: 29 September 2023 / Approved: 30 September 2023 / Online: 30 September 2023 (07:44:51 CEST)

A peer-reviewed article of this Preprint also exists.

Thimmiraju, S.R.; Adhikari, R.; Villar, M.J.; Lee, J.; Liu, Z.; Kundu, R.; Chen, Y.-L.; Sharma, S.; Ghei, K.; Keegan, B.; Versteeg, L.; Gillespie, P.M.; Ciciriello, A.; Islam, N.Y.; Poveda, C.; Uzcategui, N.; Chen, W.-H.; Kimata, J.T.; Zhan, B.; Strych, U.; Bottazzi, M.E.; Hotez, P.J.; Pollet, J. A Recombinant Protein XBB.1.5 RBD/Alum/CpG Vaccine Elicits High Neutralizing Antibody Titers against Omicron Subvariants of SARS-CoV-2. Vaccines 2023, 11, 1557. Thimmiraju, S.R.; Adhikari, R.; Villar, M.J.; Lee, J.; Liu, Z.; Kundu, R.; Chen, Y.-L.; Sharma, S.; Ghei, K.; Keegan, B.; Versteeg, L.; Gillespie, P.M.; Ciciriello, A.; Islam, N.Y.; Poveda, C.; Uzcategui, N.; Chen, W.-H.; Kimata, J.T.; Zhan, B.; Strych, U.; Bottazzi, M.E.; Hotez, P.J.; Pollet, J. A Recombinant Protein XBB.1.5 RBD/Alum/CpG Vaccine Elicits High Neutralizing Antibody Titers against Omicron Subvariants of SARS-CoV-2. Vaccines 2023, 11, 1557.

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, serum from vaccinated mice demonstrated potent neutralization against the XBB.1.5 pseudovirus as well as several other Omicron pseudoviruses. However, regardless of high antibody cross-reactivity by 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 by sera from mice vaccinated with the WT RBD/CpG/Alum vaccine or with the BA.4/5-based vaccine, 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.

Keywords

Immune escape; Vaccine efficacy; COVID-19; SARS-CoV-2

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Comments (1)

Comment 1

Received: 30 September 2023
Commenter: Jeroen Pollet
Commenter's Conflict of Interests: Author

Comment: Revised paper after peer-review
Additional data added to show protection against the EG.5 SARS-COV-2 variant

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