Intranasal Immunization with a Vaccinia Virus Vaccine Vector Expressing Pre-Fusion Stabilized SARS-CoV-2 Spike Fully Protected Mice against Lethal Challenge with the Heavily Mutated Mouse-Adapted SARS2-N501YMA30 Strain of SARS-CoV-2

Karen V. Kibler; Mateusz Szczerba; Douglas Lake; Alexa J. Roeder; Masmudur Rahman; Brenda G. Hogue; Lok-Yin Roy Wong; Stanley Perlman; Yize Li; Bertram L. Jacobs

doi:10.3390/vaccines10081172

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Intranasal Immunization with a Vaccinia Virus Vaccine Vector Expressing Pre-Fusion Stabilized SARS-CoV-2 Spike Fully Protected Mice against Lethal Challenge with the Heavily Mutated Mouse-Adapted SARS2-N501YMA30 Strain of SARS-CoV-2

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Intranasal Immunization with a Vaccinia Virus Vaccine Vector Expressing Pre-Fusion Stabilized SARS-CoV-2 Spike Fully Protected Mice against Lethal Challenge with the Heavily Mutated Mouse-Adapted SARS2-N501YMA30 Strain of SARS-CoV-2

Karen V. Kibler, Mateusz Szczerba, Douglas Lake, Alexa J. Roeder, Masmudur Rahman, Brenda G. Hogue, Lok-Yin Roy Wong, Stanley Perlman, Yize Li and Bertram L. Jacobs

Vaccines (Basel), Vol.10(1172), p.1172

07/01/2022

DOI: 10.3390/vaccines10081172

PMCID: PMC9394475

PMID: 35893821

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Abstract

The Omicron SARS-CoV-2 variant has been designated as a variant of concern because its spike protein is heavily mutated. In particular, the Omicron spike is mutated at five positions (K417, N440, E484, Q493, and N501) that have been associated with escape from neutralizing antibodies induced by either infection with or immunization against the early Washington strain of SARS-CoV-2. The mouse-adapted strain of SARS-CoV-2, SARS2-N501YMA30, contains a spike that is also heavily mutated, with mutations at four of the five positions in the Omicron spike associated with neutralizing antibody escape (K417, E484, Q493, and N501). In this manuscript, we show that intranasal immunization with a pre-fusion stabilized Washington strain spike, expressed from a highly attenuated, replication-competent vaccinia virus construct, NYVAC-KC, fully protected mice against symptoms and death from SARS2-N501YMA30. Similarly, immunization by scarification on the skin fully protected against death, but not from mild disease. This data demonstrates that the Washington strain spike, when expressed from a highly attenuated, replication-competent poxvirus—administered without parenteral injection—can fully protect against the heavily mutated mouse-adapted SARS2-N501YMA30.

replication-competent

SARS-CoV-2

vaccine

Details

Title: Subtitle: Intranasal Immunization with a Vaccinia Virus Vaccine Vector Expressing Pre-Fusion Stabilized SARS-CoV-2 Spike Fully Protected Mice against Lethal Challenge with the Heavily Mutated Mouse-Adapted SARS2-N501YMA30 Strain of SARS-CoV-2
Creators: Karen V. Kibler - Arizona State University
Mateusz Szczerba - Arizona State University
Douglas Lake - Arizona State University
Alexa J. Roeder - Arizona State University
Masmudur Rahman - Arizona State University
Brenda G. Hogue - Arizona State University
Lok-Yin Roy Wong - University of Iowa
Stanley Perlman - University of Iowa
Yize Li - Arizona State University
Bertram L. Jacobs - Arizona State University
Resource Type: Journal article
Publication Details: Vaccines (Basel), Vol.10(1172), p.1172
DOI: 10.3390/vaccines10081172
PMID: 35893821
PMCID: PMC9394475
NLM abbreviation: Vaccines (Basel)
eISSN: 2076-393X
Publisher: MDPI AG
Grant note: DOI: 10.13039/100007482, name: Arizona State University, award: GF000000002391
Language: English
Date published: 07/01/2022
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9984288742202771

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