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Volume 12
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10.3390/vaccines12040362
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Article

Multivalent and Sequential Heterologous Spike Protein Vaccinations Effectively Induce Protective Humoral Immunity against SARS-CoV-2 Variants

by
Rong Liu
1,†,
Janhavi P. Natekar
2,†,
Ki-Hye Kim
1,
Heather Pathak
2,
Noopur Bhatnagar
1,
Jannatul Ruhan Raha
1,
Bo Ryoung Park
1,
Anchala Guglani
2,
Chong Hyun Shin
1,
Mukesh Kumar
2,* and
Sang-Moo Kang
1,*
1
Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA
2
Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, GA 30303, USA
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Vaccines 2024, 12(4), 362; https://doi.org/10.3390/vaccines12040362
Submission received: 6 March 2024 / Revised: 23 March 2024 / Accepted: 26 March 2024 / Published: 27 March 2024
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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Abstract

The emergence of new SARS-CoV-2 variants continues to cause challenging problems for the effective control of COVID-19. In this study, we tested the hypothesis of whether a strategy of multivalent and sequential heterologous spike protein vaccinations would induce a broader range and higher levels of neutralizing antibodies against SARS-CoV-2 variants and more effective protection than homologous spike protein vaccination in a mouse model. We determined spike-specific IgG, receptor-binding inhibition titers, and protective efficacy in the groups of mice that were vaccinated with multivalent recombinant spike proteins (Wuhan, Delta, Omicron), sequentially with heterologous spike protein variants, or with homologous spike proteins. Trivalent (Wuhan + Delta + Omicron) and sequential heterologous spike protein vaccinations were more effective in inducing serum inhibition activities of receptor binding to spike variants and virus neutralizing antibody titers than homologous spike protein vaccination. The higher efficacy of protection was observed in mice with trivalent and sequential heterologous spike protein vaccination after a challenge with a mouse-adapted SARS-CoV-2 MA10 strain compared to homologous spike protein vaccination. This study provides evidence that a strategy of multivalent and sequential heterologous variant spike vaccination might provide more effective protection against emerging SARS-CoV-2 variants than homologous spike vaccination and significantly alleviate severe inflammation due to COVID-19.
Keywords: SARS-CoV-2; spike; sequential heterologous vaccination; multivalent vaccine; neutralizing activity SARS-CoV-2; spike; sequential heterologous vaccination; multivalent vaccine; neutralizing activity

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MDPI and ACS Style

Liu, R.; Natekar, J.P.; Kim, K.-H.; Pathak, H.; Bhatnagar, N.; Raha, J.R.; Park, B.R.; Guglani, A.; Shin, C.H.; Kumar, M.; et al. Multivalent and Sequential Heterologous Spike Protein Vaccinations Effectively Induce Protective Humoral Immunity against SARS-CoV-2 Variants. Vaccines 2024, 12, 362. https://doi.org/10.3390/vaccines12040362

AMA Style

Liu R, Natekar JP, Kim K-H, Pathak H, Bhatnagar N, Raha JR, Park BR, Guglani A, Shin CH, Kumar M, et al. Multivalent and Sequential Heterologous Spike Protein Vaccinations Effectively Induce Protective Humoral Immunity against SARS-CoV-2 Variants. Vaccines. 2024; 12(4):362. https://doi.org/10.3390/vaccines12040362

Chicago/Turabian Style

Liu, Rong, Janhavi P. Natekar, Ki-Hye Kim, Heather Pathak, Noopur Bhatnagar, Jannatul Ruhan Raha, Bo Ryoung Park, Anchala Guglani, Chong Hyun Shin, Mukesh Kumar, and et al. 2024. "Multivalent and Sequential Heterologous Spike Protein Vaccinations Effectively Induce Protective Humoral Immunity against SARS-CoV-2 Variants" Vaccines 12, no. 4: 362. https://doi.org/10.3390/vaccines12040362

APA Style

Liu, R., Natekar, J. P., Kim, K.-H., Pathak, H., Bhatnagar, N., Raha, J. R., Park, B. R., Guglani, A., Shin, C. H., Kumar, M., & Kang, S.-M. (2024). Multivalent and Sequential Heterologous Spike Protein Vaccinations Effectively Induce Protective Humoral Immunity against SARS-CoV-2 Variants. Vaccines, 12(4), 362. https://doi.org/10.3390/vaccines12040362

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