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 Rani
dc.contributor.authorAdhikari, Rakesh
dc.contributor.authorVillar, Maria Jose
dc.contributor.authorLee, Jungsoon
dc.contributor.authorLiu, Zhuyun
dc.contributor.authorKundu, Rakhi
dc.contributor.authorChen, Yi-Lin
dc.contributor.authorSharma, Suman
dc.contributor.authorGhei, Karm
dc.contributor.authorKeegan, Brian
dc.contributor.authorVersteeg, Leroy
dc.contributor.authorGillespie, Portia M.
dc.contributor.authorCiciriello, Allan
dc.contributor.authorIslam, Nelufa Y.
dc.contributor.authorPoveda, Cristina
dc.contributor.authorUzcategui, Nestor
dc.contributor.authorChen, Wen-Hsiang
dc.contributor.authorKimata, Jason T.
dc.contributor.authorZhan, Bin
dc.contributor.authorStrych, Ulrich
dc.contributor.authorBottazzi, Maria Elena
dc.contributor.authorHotez, Peter J.
dc.contributor.authorPollet, Jeroen
dc.date.accessioned2024-05-03T15:51:21Z
dc.date.available2024-05-03T15:51:21Z
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.
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/vaccines11101557
dc.identifier.digitalvaccines-11-01557
dc.identifier.urihttps://hdl.handle.net/1911/115633
dc.titleA 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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