Preclinical evaluation of a SARS-CoV-2 variant B.1.351-based candidate DNA vaccine.

Preclinical evaluation of a SARS-CoV-2 variant B.1.351-based candidate DNA vaccine.

Publication date: Sep 17, 2023

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 in response to 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), pNTC-Spike. 351, and, in animal models, compare its immunogenicity with a similar DNA vaccine encoding the ancestral index strain spike protein, pNTC-Spike. Both DNA vaccines induced neutralizing antibodies and a Th1 biased immune response. In contrast to the index-specific vaccine, the Beta-specific DNA vaccine induced antibodies in mice and rabbits that, even at low levels, efficiently neutralize the otherwise 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 pNTC-Spike. 351 to broaden neutralizing antibody responses against emerging variants of concern.

Concepts Keywords
Biased Animal model
E484k B.1.351
Models Beta variant vaccine
Rabbits Coronavirus
Vaccine DNA vaccine
T cell responses


Type Source Name
disease VO DNA vaccine
disease VO vaccine
disease MESH Covid-19
disease VO vaccine candidate
disease IDO immune response
disease VO immunization
disease IDO cell

Original Article

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