Optimized intramuscular immunization with VSV-vectored spike protein triggers a superior protective humoral immune response to SARS-CoV-2

Immunization with vesicular stomatitis virus (VSV)-vectored COVID-19 vaccine candidates expressing the SARS-CoV-2 spike protein in place of the VSV glycoprotein relies implicitly on expression of the ACE2 receptor at the muscular injection site. Here, we report that such a viral vector vaccine did n...

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Bibliographic Details
Published in:bioRxiv 2022-06
Main Authors: Taddeo, Adriano, Ines Berenguer Veiga, Devisme, Christelle, Boss, Renate, Plattet, Philippe, Weigang, Sebastian, Kochs, Georg, Thiel, Volker, Benarafa, Charaf, Zimmer, Gert
Format: Article
Language:English
Subjects:
ACE2
Angiotensin-converting enzyme 2
Coronaviruses
COVID-19 vaccines
Glycoproteins
Immune response (humoral)
Immunization
Lethal dose
Severe acute respiratory syndrome coronavirus 2
Spike protein
Stomatitis
Transgenic mice
Vaccines
Vectors (Biology)
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Summary:Immunization with vesicular stomatitis virus (VSV)-vectored COVID-19 vaccine candidates expressing the SARS-CoV-2 spike protein in place of the VSV glycoprotein relies implicitly on expression of the ACE2 receptor at the muscular injection site. Here, we report that such a viral vector vaccine did not induce protective immunity following intramuscular immunization of K18-hACE2 transgenic mice. However, when the viral vector was trans-complemented with the VSV glycoprotein, intramuscular immunization resulted in high titers of spike-specific neutralizing antibodies. The vaccinated animals were fully protected following infection with a lethal dose of SARS-CoV-2-SD614G via the nasal route, and partially protected if challenged with the SARS-CoV-2Delta variant. While dissemination of the challenge virus to the brain was completely inhibited, replication in the lung with consequent lung pathology was not entirely controlled. Thus, intramuscular immunization was clearly enhanced by trans-complementation of the VSV-vectored vaccines by the VSV glycoprotein and led to protection from COVID-19, although not achieving sterilizing immunity. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2022.06.14.495413