Preclinical Evaluation of a SARS-CoV-2 Variant B.1.351-Based Candidate DNA Vaccine
32 Pages Posted: 12 Apr 2023
Abstract
The SARS-CoV-2 pandemic revealed the critical shortfalls of global vaccine availability for emergent pathogens and the need for exploring additional vaccine platforms with rapid update potential targeting new variants. Thus, it remains essential, for the present evolving SARS-CoV-2/Covid-19 and future pandemics, to continuously develop and characterize new and different vaccine platforms. Here, we describe an expression-optimized DNA vaccine candidate based on the SARS-CoV-2 spike protein of the Beta variant (B.1.351) and, in animal models, compared its immunogenicity with a similar DNA vaccine encoding the index strain spike protein. Both DNA vaccines induced neutralizing antibodies and a Th1 biased immune response. In contrast to the ancestral index-specific vaccine, the Beta-specific DNA vaccine induced antibodies in mice and rabbits that, even at low levels, efficiently neutralize the antibody resistant Beta variant. It similarly neutralized unrelated variants bearing the neutralization resistant E484K spike mutation. Intensive priming using two vaccinations with pNTC-Spike and a single booster immunization with the pNTC-Spike.351 induced a more robust neutralizing antibody response with comparable magnitude against different variants of concern. Thus, DNA vaccine technology with heterologous spike protein prime-boost should be explored further using the Beta derived pNCT-Spike.351 to broaden neutralizing antibody responses against emerging variants of concern.
Note:
Funding Information: No particular funding was obtained for this work, which was a part of the Danish national health response to the COVID-19 pandemic.
Declaration of Interests: A.F. and C.P. are co-inventors on a patent application covering a SARS CoV-2 DNA vaccine; all rights to the vaccine have been assigned to Statens Serum Institut (SSI), a Danish national not-for-profit governmental public health institute. Other authors declare that there are no competing interests.
Ethics Approval Statement: Animal husbandry and procedures were carried out in accordance with the Animal Experimentation Act of Denmark and the European Convention ETS 123 and approved by the Danish Animal Experiments Inspectorate (2017-15-0201-01322).
Keywords: DNA vaccine, SARS-CoV-2, Beta variant vaccine, B.1.351, Immunogenicity, animal model
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