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

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dc.contributor.authorThimmiraju, Syamala Ranien_US
dc.contributor.authorAdhikari, Rakeshen_US
dc.contributor.authorVillar, Maria Joseen_US
dc.contributor.authorLee, Jungsoonen_US
dc.contributor.authorLiu, Zhuyunen_US
dc.contributor.authorKundu, Rakhien_US
dc.contributor.authorChen, Yi-Linen_US
dc.contributor.authorSharma, Sumanen_US
dc.contributor.authorGhei, Karmen_US
dc.contributor.authorKeegan, Brianen_US
dc.contributor.authorVersteeg, Leroyen_US
dc.contributor.authorGillespie, Portia M.en_US
dc.contributor.authorCiciriello, Allanen_US
dc.contributor.authorIslam, Nelufa Y.en_US
dc.contributor.authorPoveda, Cristinaen_US
dc.contributor.authorUzcategui, Nestoren_US
dc.contributor.authorChen, Wen-Hsiangen_US
dc.contributor.authorKimata, Jason T.en_US
dc.contributor.authorZhan, Binen_US
dc.contributor.authorStrych, Ulrichen_US
dc.contributor.authorBottazzi, Maria Elenaen_US
dc.contributor.authorHotez, Peter J.en_US
dc.contributor.authorPollet, Jeroenen_US
dc.date.accessioned2024-05-03T15:51:21Zen_US
dc.date.available2024-05-03T15:51:21Zen_US
dc.date.issued2023en_US
dc.description.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.en_US
dc.identifier.citationThimmiraju, 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., … Pollet, J. (2023). A Recombinant Protein XBB.1.5 RBD/Alum/CpG Vaccine Elicits High Neutralizing Antibody Titers against Omicron Subvariants of SARS-CoV-2. Vaccines, 11(10), Article 10. https://doi.org/10.3390/vaccines11101557en_US
dc.identifier.digitalvaccines-11-01557en_US
dc.identifier.urihttps://hdl.handle.net/1911/115633en_US
dc.titleA Recombinant Protein XBB.1.5 RBD/Alum/CpG Vaccine Elicits High Neutralizing Antibody Titers against Omicron Subvariants of SARS-CoV-2en_US
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