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RelCoVax®, a two antigen subunit protein vaccine candidate against SARS-CoV-2 induces strong immune responses in mice

View ORCID ProfileAbhishek Phatarphekar, G. E. C. Vidyadhar Reddy, Abhiram Gokhale, Gopala Karanam, Pushpa Kuchroo, Ketaki Shinde, Girish Masand, Shyam Pagare, Nilesh Khadpe, Sangita S. Pai, Vijita Vijayan, R. L. Ramnath, K. Pratap Reddy, Praveen Rao, S. Harinarayana Rao, Venkata Ramana
doi: https://doi.org/10.1101/2022.01.07.475330
Abhishek Phatarphekar
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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  • ORCID record for Abhishek Phatarphekar
  • For correspondence: abhishek1.p@ril.com
G. E. C. Vidyadhar Reddy
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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Abhiram Gokhale
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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Gopala Karanam
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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Pushpa Kuchroo
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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Ketaki Shinde
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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Girish Masand
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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Shyam Pagare
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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Nilesh Khadpe
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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Sangita S. Pai
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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Vijita Vijayan
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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R. L. Ramnath
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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K. Pratap Reddy
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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Praveen Rao
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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S. Harinarayana Rao
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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Venkata Ramana
1Dhirubhai Ambani Life Sciences Centre, Reliance Life Sciences Pvt. Ltd., Rabale, Navi Mumbai 400701, Maharashtra, India
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  • Abstract
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Abstract

The COVID-19 pandemic has spurred an unprecedented movement to develop safe and effective vaccines against the SARS-CoV-2 virus to immunize the global population. The first set of vaccine candidates that received emergency use authorization targeted the spike (S) glycoprotein of the SARS-CoV-2 virus that enables virus entry into cells via the receptor binding domain (RBD). Recently, multiple variants of SARS-CoV-2 have emerged with mutations in S protein and the ability to evade neutralizing antibodies in vaccinated individuals. We have developed a dual RBD and nucleocapsid (N) subunit protein vaccine candidate named RelCoVax® through heterologous expression in mammalian cells (RBD) and E. coli (N). The RelCoVax® formulation containing a combination of aluminum hydroxide (alum) and a synthetic CpG oligonucleotide as adjuvants elicited high antibody titers against RBD and N proteins in mice after a prime and boost dose regimen administered 2 weeks apart. The vaccine also stimulated cellular immune responses with a potential Th1 bias as evidenced by increased IFN-γ release by splenocytes from immunized mice upon antigen exposure particularly N protein. Finally, the serum of mice immunized with RelCoVax® demonstrated the ability to neutralize two different SARS-CoV-2 viral strains in vitro including the Delta strain that has become dominant in many regions of the world and can evade vaccine induced neutralizing antibodies. These results warrant further evaluation of RelCoVax® through advanced studies and contribute towards enhancing our understanding of multicomponent subunit vaccine candidates against SARS-CoV-2.

Competing Interest Statement

All authors are employees of Reliance Life Sciences Pvt. Ltd. and have no other competing financial interests or personal relationships to disclose.

  • Abbreviations

    ACE2
    angiotensin converting enzyme 2
    CHO
    Chinese hamster ovary
    CI
    confidence interval
    COVID-19
    Corona virus disease 19
    CpG
    cytosine phospho guanine
    E. coli
    Escherichia coli
    ELISA
    enzyme linked immunosorbent assay
    ELISpot
    Enzyme linked immunosorbent spot
    GMT
    geometric mean titer
    IFN-γ
    interferon-γ
    IgG
    immunoglobulin G
    N
    nucleocapsid
    pfu
    plaque forming units
    pRNT
    plaque reduction neutralization test
    RBD
    receptor binding domain
    SARS-CoV-2
    Severe acute respiratory syndrome Corona virus 2
    S
    spike
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    Posted January 10, 2022.
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    RelCoVax®, a two antigen subunit protein vaccine candidate against SARS-CoV-2 induces strong immune responses in mice
    Abhishek Phatarphekar, G. E. C. Vidyadhar Reddy, Abhiram Gokhale, Gopala Karanam, Pushpa Kuchroo, Ketaki Shinde, Girish Masand, Shyam Pagare, Nilesh Khadpe, Sangita S. Pai, Vijita Vijayan, R. L. Ramnath, K. Pratap Reddy, Praveen Rao, S. Harinarayana Rao, Venkata Ramana
    bioRxiv 2022.01.07.475330; doi: https://doi.org/10.1101/2022.01.07.475330
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    RelCoVax®, a two antigen subunit protein vaccine candidate against SARS-CoV-2 induces strong immune responses in mice
    Abhishek Phatarphekar, G. E. C. Vidyadhar Reddy, Abhiram Gokhale, Gopala Karanam, Pushpa Kuchroo, Ketaki Shinde, Girish Masand, Shyam Pagare, Nilesh Khadpe, Sangita S. Pai, Vijita Vijayan, R. L. Ramnath, K. Pratap Reddy, Praveen Rao, S. Harinarayana Rao, Venkata Ramana
    bioRxiv 2022.01.07.475330; doi: https://doi.org/10.1101/2022.01.07.475330

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