Improved COVID-19 vector vaccine candidate
Mittelhäusern and Bern, 02.08.2022 - In response to the SARS-CoV-2 pandemic, numerous research projects have been launched to develop vaccines against this emerging pathogen. In a recent publication in the Nature portfolio journal “npj vaccines”, scientists at the Institute of Virology and Immunology (IVI) and the University of Bern report on a Vesicular Stomatitis Virus (VSV)-vectored COVID-19 vaccine candidate. Their work shows that intramuscular immunization of mice with VSV-vectored COVID-19 vaccines is inducing strong antibody responses against the SARS-CoV-2 spike protein only if the vector has been complemented with the VSV glycoprotein G.
A COVID-19 vaccine candidate based on the vesicular stomatitis virus (VSV) vector encoding the SARS-CoV-2 spike antigen was developed in the USA and Israel. Although initial pre-clinical experiments showed promising results in Syrian hamster models, human volunteers did not mount proper immune responses to immunization and therefore further development of the vaccine candidate was abandoned. The research groups headed by Gert Zimmer and Charaf Benarafa of the IVI and University of Bern further explored this vector vaccine platform and solved the challenge to develop a VSV-vectored COVID-19 vaccine candidate with superior performance. They found that by adding the VSV G glycoprotein to the viral vector, intramuscular immunization resulted in high titers of spike antigen-specific neutralizing antibodies, even after a single immunization. Using this optimized vaccine, immunized mice were fully protected against a lethal dose of SARS-CoV-2 administered by the nasal route and partially protected if challenged with the Delta variant of SARS-CoV-2.
After this success in preclinical animal models, the improved formulation of this new COVID-19 vaccine candidate developed by the IVI may enter clinical studies to evaluate its safety and effectiveness in human volunteers. Gert Zimmer, principal investigator in the virology department says : “In the present work, the VSV-vectored vaccine was administered via the intramuscular route, which protected mice from severe disease but did not completely block virus replication in the respiratory tract. This is not that surprising given that the intramuscular route of vaccination does not sufficiently induce mucosal immunity. Only the induction of local immune responses will help to block SARS-CoV-2 at sites of primary replication and may prevent virus transmission.” Thus, future work will also focus on immunization regimens that can trigger strong and long-lasting mucosal immunity to SARS-CoV-2.
This discovery could be applicable to other diseases than COVID-19
Vesicular stomatitis virus VSV represents a powerful vector platform, which can be applied to other diseases that are caused by viral pathogens such as MERS coronavirus, HIV-1, hepatitis C virus, or influenza A virus. Moreover, a VSV vaccine has already been approved against Ebola haemorrhagic fever.
The technology described in the present work will certainly help to improve vector production, delivery, and safety for all these VSV-based vaccine candidates in future. With respect to SARS-CoV-2, the new technology may complement existing vaccine approaches to improve immunity.
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