Multivalent and Sequential Heterologous Spike Protein Vaccinations Effectively Induce Protective Humoral Immunity against SARS-CoV-2 Variants
Abstract
:1. Introduction
2. Material and Methods
2.1. Recombinant Proteins and Reagents
2.2. Vaccination
2.3. Inhibition Assay of hACE2 Binding to Spike Proteins
2.4. Enzyme-Linked Immunosorbent Assay (ELISA)
2.5. SARS-CoV-2 Challenge
2.6. Lung Viral Titration
2.7. Plaque Reduction Neutralization Test (PRNT)
2.8. Cytokine and Chemokine Analysis
2.9. Statistical Analysis
3. Result
3.1. Heterologous or Trivalent Spike Protein Vaccinations More Effectively Induce Cross-Reactive IgG Antibodies Than Wuhan Spike Homologous Vaccine
3.2. Heterologous Sequential Spike Protein and Trivalent Spike Vaccinations Induce Higher Levels of Receptor Binding Inhibition Activities and SARS-CoV-2 Neutralizing Titers
3.3. Heterologous Sequential and Trivalent Spike Vaccinations Induce Higher Efficacy of Clearing Lung Virus and Protection against SARS-CoV-2 Than Homologous Spike Repeat Vaccination
3.4. Heterologous Sequential and Trivalent Spike Vaccinations Effectively Prevent Severe Inflammatory Responses Due to MA10 Virus Infection
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Duong, D. Alpha, Beta, Delta, Gamma: What’s important to know about SARS-CoV-2 variants of concern? Can. Med. Assoc. J. CMAJ 2021, 193, E1059–E1060. [Google Scholar] [CrossRef] [PubMed]
- McNaughton, A.L.; Paton, R.S.; Edmans, M.; Youngs, J.; Wellens, J.; Phalora, P.; Fyfe, A.; Belij-Rammerstorfer, S.; Bolton, J.S.; Ball, J.; et al. Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses. JCI Insight 2022, 7, e156372. [Google Scholar] [CrossRef] [PubMed]
- Wilks, S.H.; Mühlemann, B.; Shen, X.; Türeli, S.; LeGresley, E.B.; Netzl, A.; Caniza, M.A.; Chacaltana-Huarcaya, J.N.; Corman, V.M.; Daniell, X.; et al. Mapping SARS-CoV-2 antigenic relationships and serological responses. Science 2023, 382, eadj0070. [Google Scholar] [CrossRef] [PubMed]
- Ren, S.Y.; Wang, W.B.; Gao, R.D.; Zhou, A.M. Omicron variant (B.1.1.529) of SARS-CoV-2: Mutation, infectivity, transmission, and vaccine resistance. World J. Clin. Cases 2022, 10, 1–11. [Google Scholar] [CrossRef] [PubMed]
- Christensen, P.A.; Olsen, R.J.; Long, S.W.; Snehal, R.; Davis, J.J.; Ojeda Saavedra, M.; Reppond, K.; Shyer, M.N.; Cambric, J.; Gadd, R.; et al. Signals of Significantly Increased Vaccine Breakthrough, Decreased Hospitalization Rates, and Less Severe Disease in Patients with Coronavirus Disease 2019 Caused by the Omicron Variant of Severe Acute Respiratory Syndrome Coronavirus 2 in Houston, Texas. Am. J. Pathol. 2022, 192, 642–652. [Google Scholar] [CrossRef]
- Keyel, A.C.; Russell, A.; Plitnick, J.; Rowlands, J.V.; Lamson, D.M.; Rosenberg, E.; St George, K. SARS-CoV-2 Vaccine Breakthrough by Omicron and Delta Variants, New York, USA. Emerg. Infect. Dis. 2022, 28, 1990–1998. [Google Scholar] [CrossRef]
- McLean, G.; Kamil, J.; Lee, B.; Moore, P.; Schulz, T.F.; Muik, A.; Sahin, U.; Türeci, Ö.; Pather, S. The Impact of Evolving SARS-CoV-2 Mutations and Variants on COVID-19 Vaccines. mBio 2022, 13, e0297921. [Google Scholar] [CrossRef] [PubMed]
- Coronavirus (COVID-19) Vaccinations. Available online: https://ourworldindata.org/covid-vaccinations (accessed on 28 February 2024).
- Lau, J.J.; Cheng, S.M.S.; Leung, K.; Lee, C.K.; Hachim, A.; Tsang, L.C.H.; Yam, K.W.H.; Chaothai, S.; Kwan, K.K.H.; Chai, Z.Y.H.; et al. Real-world COVID-19 vaccine effectiveness against the Omicron BA.2 variant in a SARS-CoV-2 infection-naive population. Nat. Med. 2023, 29, 348–357. [Google Scholar] [CrossRef]
- Variant Proportions. Monitoring Variant Proportions. Available online: https://covid.cdc.gov/covid-data-tracker/#variant-proportions (accessed on 28 February 2024).
- Vogel, L. What to know about Omicron XBB.1.5. Can. Med. Assoc. J. CMAJ 2023, 195, E127–E128. [Google Scholar] [CrossRef]
- Huiberts, A.J.; de Gier, B.; Hoeve, C.E.; de Melker, H.E.; Hahné, S.J.; den Hartog, G.; van de Wijgert, J.H.; van den Hof, S.; Knol, M.J. Effectiveness of bivalent mRNA booster vaccination against SARS-CoV-2 Omicron infection, the Netherlands, September to December 2022. Eurosurveillance 2023, 28, 2300087. [Google Scholar] [CrossRef]
- Kim, K.H.; Bhatnagar, N.; Jeeva, S.; Oh, J.; Park, B.R.; Shin, C.H.; Wang, B.Z.; Kang, S.M. Immunogenicity and Neutralizing Activity Comparison of SARS-CoV-2 Spike Full-Length and Subunit Domain Proteins in Young Adult and Old-Aged Mice. Vaccines 2021, 9, 316. [Google Scholar] [CrossRef]
- Bhatnagar, N.; Kim, K.H.; Subbiah, J.; Muhammad-Worsham, S.; Park, B.R.; Liu, R.; Grovenstein, P.; Wang, B.Z.; Kang, S.M. Heterologous Prime-Boost Vaccination with Inactivated Influenza Viruses Induces More Effective Cross-Protection than Homologous Repeat Vaccination. Vaccines 2023, 11, 1209. [Google Scholar] [CrossRef] [PubMed]
- Bommireddy, R.; Stone, S.; Bhatnagar, N.; Kumari, P.; Munoz, L.E.; Oh, J.; Kim, K.H.; Berry, J.T.L.; Jacobsen, K.M.; Jaafar, L.; et al. Influenza Virus-like Particle-Based Hybrid Vaccine Containing RBD Induces Immunity against Influenza and SARS-CoV-2 Viruses. Vaccines 2022, 10, 944. [Google Scholar] [CrossRef]
- Patterson, L.D.; Dubansky, B.D.; Dubansky, B.H.; Stone, S.; Kumar, M.; Rice, C.D. Generation and Characterization of a Multi-Functional Panel of Monoclonal Antibodies for SARS-CoV-2 Research and Treatment. Viruses 2023, 16, 64. [Google Scholar] [CrossRef] [PubMed]
- Kumari, P.; Rothan, H.A.; Natekar, J.P.; Stone, S.; Pathak, H.; Strate, P.G.; Arora, K.; Brinton, M.A.; Kumar, M. Neuroinvasion and Encephalitis Following Intranasal Inoculation of SARS-CoV-2 in K18-hACE2 Mice. Viruses 2021, 13, 132. [Google Scholar] [CrossRef] [PubMed]
- Grunau, B.; Prusinkiewicz, M.; Asamoah-Boaheng, M.; Golding, L.; Lavoie, P.M.; Petric, M.; Levett, P.N.; Haig, S.; Barakauskas, V.; Karim, M.E.; et al. Correlation of SARS-CoV-2 Viral Neutralizing Antibody Titers with Anti-Spike Antibodies and ACE-2 Inhibition among Vaccinated Individuals. Microbiol. Spectr. 2022, 10, e0131522. [Google Scholar] [CrossRef] [PubMed]
- Zhang, S.; Gao, C.; Das, T.; Luo, S.; Tang, H.; Yao, X.; Cho, C.Y.; Lv, J.; Maravillas, K.; Jones, V.; et al. The spike-ACE2 binding assay: An in vitro platform for evaluating vaccination efficacy and for screening SARS-CoV-2 inhibitors and neutralizing antibodies. J. Immunol. Methods 2022, 503, 113244. [Google Scholar] [CrossRef] [PubMed]
- Leist, S.R.; Dinnon, K.H., 3rd; Schäfer, A.; Tse, L.V.; Okuda, K.; Hou, Y.J.; West, A.; Edwards, C.E.; Sanders, W.; Fritch, E.J.; et al. A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice. Cell 2020, 183, 1070–1085.e12. [Google Scholar] [CrossRef]
- Song, P.; Li, W.; Xie, J.; Hou, Y.; You, C. Cytokine storm induced by SARS-CoV-2. Clin. Chim. Acta 2020, 509, 280–287. [Google Scholar] [CrossRef]
- Zanza, C.; Romenskaya, T.; Manetti, A.C.; Franceschi, F.; La Russa, R.; Bertozzi, G.; Maiese, A.; Savioli, G.; Volonnino, G.; Longhitano, Y. Cytokine Storm in COVID-19: Immunopathogenesis and Therapy. Medicina 2022, 58, 144. [Google Scholar] [CrossRef]
- Chi, Y.; Ge, Y.; Wu, B.; Zhang, W.; Wu, T.; Wen, T.; Liu, J.; Guo, X.; Huang, C.; Jiao, Y.; et al. Serum Cytokine and Chemokine Profile in Relation to the Severity of Coronavirus Disease 2019 in China. J. Infect. Dis. 2020, 222, 746–754. [Google Scholar] [CrossRef]
- Andrews, N.; Stowe, J.; Kirsebom, F.; Toffa, S.; Rickeard, T.; Gallagher, E.; Gower, C.; Kall, M.; Groves, N.; O’Connell, A.M.; et al. Covid-19 Vaccine Effectiveness against the Omicron (B.1.1.529) Variant. N. Engl. J. Med. 2022, 386, 1532–1546. [Google Scholar] [CrossRef] [PubMed]
- Khan, M.S.; Kim, E.; Huang, S.; Kenniston, T.W.; Gambotto, A. Trivalent SARS-CoV-2 S1 Subunit Protein Vaccination Induces Broad Humoral Responses in BALB/c Mice. Vaccines 2023, 11, 314. [Google Scholar] [CrossRef] [PubMed]
- Plested, J.S.; Zhu, M.; Cloney-Clark, S.; Massuda, E.; Patel, U.; Klindworth, A.; Massare, M.J.; Cai, R.; Fries, L.; Glenn, G.; et al. Severe Acute Respiratory Syndrome Coronavirus 2 Receptor (Human Angiotensin-Converting Enzyme 2) Binding Inhibition Assay: A Rapid, High-Throughput Assay Useful for Vaccine Immunogenicity Evaluation. Microorganisms 2023, 11, 368. [Google Scholar] [CrossRef] [PubMed]
- Zhu, M.; Cloney-Clark, S.; Feng, S.L.; Parekh, A.; Gorinson, D.; Silva, D.; Skonieczny, P.; Wilson, A.; Kalkeri, R.; Woo, W.; et al. A Severe Acute Respiratory Syndrome Coronavirus 2 Anti-Spike Immunoglobulin G Assay: A Robust Method for Evaluation of Vaccine Immunogenicity Using an Established Correlate of Protection. Microorganisms 2023, 11, 1789. [Google Scholar] [CrossRef] [PubMed]
- Junker, D.; Becker, M.; Wagner, T.R.; Kaiser, P.D.; Maier, S.; Grimm, T.M.; Griesbaum, J.; Marsall, P.; Gruber, J.; Traenkle, B.; et al. Antibody Binding and Angiotensin-Converting Enzyme 2 Binding Inhibition Is Significantly Reduced for Both the BA.1 and BA.2 Omicron Variants. Clin. Infect. Dis. 2023, 76, e240–e249. [Google Scholar] [CrossRef]
- Hernandez-Davies, J.E.; Felgner, J.; Strohmeier, S.; Pone, E.J.; Jain, A.; Jan, S.; Nakajima, R.; Jasinskas, A.; Strahsburger, E.; Krammer, F.; et al. Administration of Multivalent Influenza Virus Recombinant Hemagglutinin Vaccine in Combination-Adjuvant Elicits Broad Reactivity Beyond the Vaccine Components. Front. Immunol. 2021, 12, 692151. [Google Scholar] [CrossRef] [PubMed]
- McLean, H.Q.; Thompson, M.G.; Sundaram, M.E.; Meece, J.K.; McClure, D.L.; Friedrich, T.C.; Belongia, E.A. Impact of repeated vaccination on vaccine effectiveness against influenza A(H3N2) and B during 8 seasons. Clin. Infect. Dis. 2014, 59, 1375–1385. [Google Scholar] [CrossRef]
- Leung, V.K.Y.; Carolan, L.A.; Worth, L.J.; Harper, S.A.; Peck, H.; Tilmanis, D.; Laurie, K.L.; Slavin, M.A.; Sullivan, S.G. Influenza vaccination responses: Evaluating impact of repeat vaccination among health care workers. Vaccine 2017, 35, 2558–2568. [Google Scholar] [CrossRef] [PubMed]
- Park, B.R.; Subbiah, J.; Kim, K.H.; Kwon, Y.M.; Oh, J.; Kim, M.C.; Shin, C.H.; Seong, B.L.; Kang, S.M. Enhanced cross protection by hetero prime-boost vaccination with recombinant influenza viruses containing chimeric hemagglutinin-M2e epitopes. Virology 2022, 566, 143–152. [Google Scholar] [CrossRef]
- Iketani, S.; Liu, L.; Guo, Y.; Liu, L.; Chan, J.F.; Huang, Y.; Wang, M.; Luo, Y.; Yu, J.; Chu, H.; et al. Antibody evasion properties of SARS-CoV-2 Omicron sublineages. Nature 2022, 604, 553–556. [Google Scholar] [CrossRef] [PubMed]
- Deng, W.; Lv, Q.; Li, F.; Liu, J.; Song, Z.; Qi, F.; Wei, Q.; Yu, P.; Liu, M.; Zhou, S.; et al. Sequential immunizations confer cross-protection against variants of SARS-CoV-2, including Omicron in Rhesus macaques. Signal Transduct. Target. Ther. 2022, 7, 124. [Google Scholar] [CrossRef] [PubMed]
- Shin, K.S.; Kim, B.S.; Chang, S.; Jung, I.K.; Park, H.; Park, S.; Shin, J.; Kim, J.H.; Han, S.J.; Park, B.; et al. Boosting with variant-matched adenovirus-based vaccines promotes neutralizing antibody responses against SARS-CoV-2 Omicron sublineages in mice. Int. J. Antimicrob. Agents 2023, 63, 107082. [Google Scholar] [CrossRef]
- Gu, H.; Chen, Q.; Yang, G.; He, L.; Fan, H.; Deng, Y.Q.; Wang, Y.; Teng, Y.; Zhao, Z.; Cui, Y.; et al. Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy. Science 2020, 369, 1603–1607. [Google Scholar] [CrossRef] [PubMed]
- Routhu, N.K.; Cheedarla, N.; Bollimpelli, V.S.; Gangadhara, S.; Edara, V.V.; Lai, L.; Sahoo, A.; Shiferaw, A.; Styles, T.M.; Floyd, K.; et al. SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung. Nat. Commun. 2021, 12, 3587. [Google Scholar] [CrossRef]
- Honda-Okubo, Y.; Bowen, R.; Barker, M.; Bielefeldt-Ohmann, H.; Petrovsky, N. Advax-CpG55.2-adjuvanted monovalent or trivalent SARS-CoV-2 recombinant spike protein vaccine protects hamsters against heterologous infection with Beta or Delta variants. Vaccine 2023, 41, 7116–7128. [Google Scholar] [CrossRef] [PubMed]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
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
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 StyleLiu, 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