Safety and Immunogenicity Analysis of a Newcastle Disease Virus (NDV-HXP-S) Expressing the Spike Protein of SARS-CoV-2 in Sprague Dawley Rats

Despite global vaccination efforts, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread globally. Relatively high vaccination rates have been achieved in most regions of the United States and several countries worldwide. However, access to vaccines in low- and...

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Autores principales: Johnstone Tcheou, Ariel Raskin, Gagandeep Singh, Hisaaki Kawabata, Dominika Bielak, Weina Sun, Irene González-Domínguez, D Noah Sather, Adolfo García-Sastre, Peter Palese, Florian Krammer, Juan Manuel Carreño
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:5b32844202bb44e5b26127bad0eeb6d72021-11-18T09:23:52ZSafety and Immunogenicity Analysis of a Newcastle Disease Virus (NDV-HXP-S) Expressing the Spike Protein of SARS-CoV-2 in Sprague Dawley Rats1664-322410.3389/fimmu.2021.791764https://doaj.org/article/5b32844202bb44e5b26127bad0eeb6d72021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.791764/fullhttps://doaj.org/toc/1664-3224Despite global vaccination efforts, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread globally. Relatively high vaccination rates have been achieved in most regions of the United States and several countries worldwide. However, access to vaccines in low- and mid-income countries (LMICs) is still suboptimal. Second generation vaccines that are universally affordable and induce systemic and mucosal immunity are needed. Here we performed an extended safety and immunogenicity analysis of a second-generation SARS-CoV-2 vaccine consisting of a live Newcastle disease virus vector expressing a pre-fusion stabilized version of the spike protein (NDV-HXP-S) administered intranasally (IN), intramuscularly (IM), or IN followed by IM in Sprague Dawley rats. Local reactogenicity, systemic toxicity, and post-mortem histopathology were assessed after the vaccine administration, with no indication of severe local or systemic reactions. Immunogenicity studies showed that the three vaccination regimens tested elicited high antibody titers against the wild type SARS-CoV-2 spike protein and the NDV vector. Moreover, high antibody titers were induced against the spike of B.1.1.7 (alpha), B.1.351 (beta) and B.1.617.2 (delta) variants of concern (VOCs). Importantly, robust levels of serum antibodies with neutralizing activity against the authentic SARS-CoV-2 USA‐WA1/2020 isolate were detected after the boost. Overall, our study expands the pre-clinical safety and immunogenicity characterization of NDV-HXP-S and reinforces previous findings in other animal models about its high immunogenicity. Clinical testing of this vaccination approach is ongoing in different countries including Thailand, Vietnam, Brazil and Mexico.Johnstone TcheouAriel RaskinGagandeep SinghHisaaki KawabataDominika BielakWeina SunIrene González-DomínguezD Noah SatherD Noah SatherD Noah SatherAdolfo García-SastreAdolfo García-SastreAdolfo García-SastreAdolfo García-SastreAdolfo García-SastrePeter PalesePeter PaleseFlorian KrammerFlorian KrammerJuan Manuel CarreñoFrontiers Media S.A.articleCOVID-19SARS-CoV-2newcastle disease virusvaccineimmunogenicitysafetyImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic COVID-19
SARS-CoV-2
newcastle disease virus
vaccine
immunogenicity
safety
Immunologic diseases. Allergy
RC581-607
spellingShingle COVID-19
SARS-CoV-2
newcastle disease virus
vaccine
immunogenicity
safety
Immunologic diseases. Allergy
RC581-607
Johnstone Tcheou
Ariel Raskin
Gagandeep Singh
Hisaaki Kawabata
Dominika Bielak
Weina Sun
Irene González-Domínguez
D Noah Sather
D Noah Sather
D Noah Sather
Adolfo García-Sastre
Adolfo García-Sastre
Adolfo García-Sastre
Adolfo García-Sastre
Adolfo García-Sastre
Peter Palese
Peter Palese
Florian Krammer
Florian Krammer
Juan Manuel Carreño
Safety and Immunogenicity Analysis of a Newcastle Disease Virus (NDV-HXP-S) Expressing the Spike Protein of SARS-CoV-2 in Sprague Dawley Rats
description Despite global vaccination efforts, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread globally. Relatively high vaccination rates have been achieved in most regions of the United States and several countries worldwide. However, access to vaccines in low- and mid-income countries (LMICs) is still suboptimal. Second generation vaccines that are universally affordable and induce systemic and mucosal immunity are needed. Here we performed an extended safety and immunogenicity analysis of a second-generation SARS-CoV-2 vaccine consisting of a live Newcastle disease virus vector expressing a pre-fusion stabilized version of the spike protein (NDV-HXP-S) administered intranasally (IN), intramuscularly (IM), or IN followed by IM in Sprague Dawley rats. Local reactogenicity, systemic toxicity, and post-mortem histopathology were assessed after the vaccine administration, with no indication of severe local or systemic reactions. Immunogenicity studies showed that the three vaccination regimens tested elicited high antibody titers against the wild type SARS-CoV-2 spike protein and the NDV vector. Moreover, high antibody titers were induced against the spike of B.1.1.7 (alpha), B.1.351 (beta) and B.1.617.2 (delta) variants of concern (VOCs). Importantly, robust levels of serum antibodies with neutralizing activity against the authentic SARS-CoV-2 USA‐WA1/2020 isolate were detected after the boost. Overall, our study expands the pre-clinical safety and immunogenicity characterization of NDV-HXP-S and reinforces previous findings in other animal models about its high immunogenicity. Clinical testing of this vaccination approach is ongoing in different countries including Thailand, Vietnam, Brazil and Mexico.
format article
author Johnstone Tcheou
Ariel Raskin
Gagandeep Singh
Hisaaki Kawabata
Dominika Bielak
Weina Sun
Irene González-Domínguez
D Noah Sather
D Noah Sather
D Noah Sather
Adolfo García-Sastre
Adolfo García-Sastre
Adolfo García-Sastre
Adolfo García-Sastre
Adolfo García-Sastre
Peter Palese
Peter Palese
Florian Krammer
Florian Krammer
Juan Manuel Carreño
author_facet Johnstone Tcheou
Ariel Raskin
Gagandeep Singh
Hisaaki Kawabata
Dominika Bielak
Weina Sun
Irene González-Domínguez
D Noah Sather
D Noah Sather
D Noah Sather
Adolfo García-Sastre
Adolfo García-Sastre
Adolfo García-Sastre
Adolfo García-Sastre
Adolfo García-Sastre
Peter Palese
Peter Palese
Florian Krammer
Florian Krammer
Juan Manuel Carreño
author_sort Johnstone Tcheou
title Safety and Immunogenicity Analysis of a Newcastle Disease Virus (NDV-HXP-S) Expressing the Spike Protein of SARS-CoV-2 in Sprague Dawley Rats
title_short Safety and Immunogenicity Analysis of a Newcastle Disease Virus (NDV-HXP-S) Expressing the Spike Protein of SARS-CoV-2 in Sprague Dawley Rats
title_full Safety and Immunogenicity Analysis of a Newcastle Disease Virus (NDV-HXP-S) Expressing the Spike Protein of SARS-CoV-2 in Sprague Dawley Rats
title_fullStr Safety and Immunogenicity Analysis of a Newcastle Disease Virus (NDV-HXP-S) Expressing the Spike Protein of SARS-CoV-2 in Sprague Dawley Rats
title_full_unstemmed Safety and Immunogenicity Analysis of a Newcastle Disease Virus (NDV-HXP-S) Expressing the Spike Protein of SARS-CoV-2 in Sprague Dawley Rats
title_sort safety and immunogenicity analysis of a newcastle disease virus (ndv-hxp-s) expressing the spike protein of sars-cov-2 in sprague dawley rats
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/5b32844202bb44e5b26127bad0eeb6d7
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