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