SARS-CoV-2 vaccine based on vesicular stomatitis virus exhibits high neutralizing efficacy against variants

Serum samples obtained from the recipients of the BriLife® coronavirus disease 2019 (COVID-19) vaccine candidate have shown high potency in neutralizing the alpha, beta, gamma, and delta variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Study: Neutralization of SARS-CoV-2 variants by rVSV-ΔG-spike-elicited human sera. Image Credit: Melinda Nagy/Shutterstock

BriLife®, also known as IIBR-100, is a vesicular stomatitis virus (VSV)-based, SARS-CoV-2 spike-containing vaccine developed by the Israel Institute for Biological Science, Israel.

The study is currently available on the medRxiv* preprint server.

Background

The evidence collected shortly after the initiation of global vaccination campaigns against COVID-19 has highlighted the efficacy of vaccines in preventing SARS-CoV-2 infection, symptomatic COVID-19, hospitalization, and mortality.

However, some recent evidence on vaccine breakthrough cases has raised the possibility of waning vaccine efficacy with time.

One potential reason is the emergence of novel viral variants with multiple spike mutations that can significantly affect the neutralizing potency of vaccines.

To bring an end to the pandemic, it is important to continuously monitor vaccine efficacy in the general population and develop new vaccine candidates that can effectively target emerging variants.

In the current study, the scientists have tested the efficacy of BriLife®-vaccinated human sera in neutralizing more infectious and probably more virulent SARS-CoV-2 variants, including the alpha, beta, gamma, and delta variants.

The vaccine candidate

BriLife® is a VSV-based, replication-competent COVID-19 vaccine candidate in which the surface glycoprotein of VSV has been replaced with the spike glycoprotein of the original SARS-CoV-2 strain.

The study

The scientists collected serum samples from the participants of the BriLife® phase II clinical trial after two weeks of intramuscular prime-boost immunization.

In one part of the study, they tested the efficacy of nine serum samples in neutralizing the original SARS-CoV-2 strain and alpha, beta, and gamma variants. In another part of the study, they tested the efficacy of eleven serum samples in neutralizing the original SARS-CoV-2 strain and the delta variant.

In a separate set of experiments, they tested the virus-neutralizing efficacy of nine serum samples obtained from COVID-19 recovered individuals.

Important observations

Nine serum samples tested in one part of the study showed significant efficacy in neutralizing both the wild-type SARS-CoV-2 and the gamma variant. Compared to the wild-type virus, a 1.5-fold and 2.4-fold reduced neutralizing efficacy was observed against the alpha and beta variants, respectively.

In the other part of the study, almost all serum samples that neutralized the wild-type virus showed similar efficacy in neutralizing the delta variant. In contrast, serum samples collected from COVID-19 recovered individuals showed 3.8-fold reduced neutralizing efficacy against the delta variant compared to that against the wild-type virus.

However, the convalescent sera showed comparable efficacy against the wild-type virus and the alpha, beta, and gamma variants.

Advantages of the vaccine candidate

One of the potential disadvantages of viral vector-based vaccines is the development of vector immunity. Vector immunity refers to the induction of innate immune response against the surface antigens of viral vectors, such as adenoviral vectors. This could potentially reduce vaccine efficacy upon repeated immunizations.

In BriLife®, the risk of vector immunity was reduced by replacing the surface antigen of VSV with SARS-CoV-2 spike. Upon vaccination with BriLife®, no significant induction of vector immunity was observed in the study.

The development of this vaccine candidate was accompanied by the spontaneous acquisition of multiple mutations, some of which are naturally present in newly emerged viral variants. These mutations are N501Y and E484D located at the spike receptor-binding domain (RBD) and R685G located at the furin cleavage site in the junction of S1 and S2 subunits. The viral variants with these spike mutations have been found to have increased ability to escape antibody-mediated neutralization.

The spontaneous acquisition of N501Y and E484D spike mutations during the development of BriLife® might be attributed to its high neutralizing efficacy against tested viral variants.

Study significance

The study findings reveal that antibodies induced in response to the BriLife® vaccine can effectively neutralize a wide range of SARS-CoV-2 variants, including the delta variant.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.