VSV-Based Vaccines Reduce Virus Shedding and Viral Load in Hamsters Infected with SARS-CoV-2 Variants of Concern

Abstract

The continued progression of the COVID-19 pandemic can partly be attributed to the ability of SARS-CoV-2 to mutate and introduce new viral variants. Some of these variants with the potential to spread quickly and conquer the globe are termed variants of concern (VOC). The existing vaccines implemented on a global scale are based on the ancestral strain, which has resulted in increased numbers of breakthrough infections as these VOC have emerged. It is imperative to show protection against VOC infection with newly developed vaccines. Previously, we evaluated two vesicular stomatitis virus (VSV)-based vaccines expressing the SARS-CoV-2 spike protein alone (VSV-SARS2) or in combination with the Ebola virus glycoprotein (VSV-SARS2-EBOV) and demonstrated their fast-acting potential. Here, we prolonged the time to challenge; we vaccinated hamsters intranasally (IN) or intramuscularly 28 days prior to infection with three SARS-CoV-2 VOC—the Alpha, Beta, and Delta variants. IN vaccination with either the VSV-SARS2 or VSV-SARS2-EBOV resulted in the highest protective efficacy as demonstrated by decreased virus shedding and lung viral load of vaccinated hamsters. Histopathologic analysis of the lungs revealed the least amount of lung damage in the IN-vaccinated animals regardless of the challenge virus. This data demonstrates the ability of a VSV-based vaccine to not only protect from disease caused by SARS-CoV-2 VOC but also reduce viral shedding.

Preclinical immunogenicity and efficacy of a candidate COVID-19 vaccine based on a vesicular stomatitis virus-SARS-CoV-2 chimera

“…Some of the preclinical data presented here provide useful context for considering the basis for the low immunogenicity of the single IM dose of VSV∆G-SARS-CoV-2 #9 observed in the phase 1 clinical trial. 18 Yet, more importantly, the research described here, as well as by others 50 , 86 also provides encouraging data to support the development and further evaluation of an intranasal VSV∆G-SARS-CoV-2 vaccine that could help prevent upper respiratory tract infection by SARS-CoV-2 and reduce transmission from asymptomatic infected individuals.…”

“…This method of IN vaccination caused no observable adverse reactions in the hamsters ( Figure 7 d) and produced a robust systemic immune response with doses as low as 1000 PFU ( Figure 7 b and c), supporting the interpretation that IN vaccination is an effective method for VSV∆G-SARS-CoV-2 delivery in hamsters, as also concluded by others. 50 , 86 …”

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

“…Immunization via the intramuscular route can induce antibodies of the IgA isotype, which are efficiently secreted into the mucosal tissues of the respiratory tract where they can directly neutralize pathogens at the site of primary replication 33 , 34 . In contrast to the presently approved mRNA vaccines, which rely on intramuscular administration, there is already first evidence from the hamster model that mucosally applied VSV-vectored COVID-19 vaccines can in principle be very effective in preventing virus shedding from the respiratory tract 32 , 35 . Recently, VSV-vectored spike antigen that was administered via the oral route efficiently boosted the immune response to SARS-CoV-2 in nonhuman primates 36 .…”

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

“…33, 34 In contrast to the presently approved mRNA vaccines, which rely on intramuscular administration, there is already first evidence from the hamster model that mucosally applied VSV-vectored COVID-19 vaccines can in principle be very effective in preventing virus shedding from the respiratory tract. 32, 35 Recently, VSV-vectored spike antigen that was administered via the oral route efficiently boosted the immune response to SARS-CoV-2 in nonhuman primates. 36…”

“…33,34 In contrast to the presently approved mRNA vaccines, which rely on intramuscular administration, there is already first evidence from the hamster model that mucosally applied VSV-vectored COVID-19 vaccines can in principle be very effective in preventing virus shedding from the respiratory tract. 32,35 Recently, VSV-vectored spike antigen that was administered via the oral route efficiently boosted the immune response to SARS-CoV-2 in nonhuman primates. 36 In summary, our findings demonstrate that trans-complementation of VSV-vectored vaccines with the VSV G protein has multiple impacts: (1) it improves virus yield to maximize vaccine production, (2) it allows efficient ACE2-independent intramuscular immunization leading to dramatically enhanced immune responses even after a single administration, (3) it supports the induction of broadly neutralizing antibodies when associated with the proper antigen.…”