Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT™ adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice

The speed at which several COVID-19 vaccines went from conception to receiving FDA and EMA approval for emergency use is an achievement unrivaled in the history of vaccine development. Mass vaccination efforts using the highly effective vaccines are currently underway to generate sufficient herd imm...

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Autores principales: Chih-Yun Lai, Albert To, Teri Ann S. Wong, Michael M. Lieberman, David E. Clements, James T. Senda, Aquena H. Ball, Laurent Pessaint, Hanne Andersen, Wakako Furuyama, Andrea Marzi, Oreola Donini, Axel T. Lehrer
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Publicado: Elsevier 2021
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spelling oai:doaj.org-article:4899da1012804294873b875b8874ede52021-11-26T04:39:02ZRecombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT™ adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice2590-136210.1016/j.jvacx.2021.100126https://doaj.org/article/4899da1012804294873b875b8874ede52021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2590136221000437https://doaj.org/toc/2590-1362The speed at which several COVID-19 vaccines went from conception to receiving FDA and EMA approval for emergency use is an achievement unrivaled in the history of vaccine development. Mass vaccination efforts using the highly effective vaccines are currently underway to generate sufficient herd immunity and reduce transmission of the SARS-CoV-2 virus. Despite the most advanced vaccine technology, global recipient coverage, especially in resource-poor areas remains a challenge as genetic drift in naïve population pockets threatens overall vaccine efficacy. In this study, we described the production of insect-cell expressed SARS-CoV-2 spike protein ectodomain constructs and examined their immunogenicity in mice. We demonstrated that, when formulated with CoVaccine HTTM adjuvant, an oil-in-water nanoemulsion compatible with lyophilization, our vaccine candidates elicit a broad-spectrum IgG response, high neutralizing antibody (NtAb) titers against SARS-CoV-2 prototype and variants of concern, specifically B.1.351 (Beta) and P.1. (Gamma), and an antigen-specific IFN-γ secreting response in outbred mice. Of note, different ectodomain constructs yielded variations in NtAb titers against the prototype strain and some VOC. Dose response experiments indicated that NtAb titers increased with antigen dose, but not adjuvant dose, and may be higher with a lower adjuvant dose. Our findings lay the immunological foundation for the development of a dry-thermostabilized vaccine that is deployable without refrigeration.Chih-Yun LaiAlbert ToTeri Ann S. WongMichael M. LiebermanDavid E. ClementsJames T. SendaAquena H. BallLaurent PessaintHanne AndersenWakako FuruyamaAndrea MarziOreola DoniniAxel T. LehrerElsevierarticleSARS-CoV-2 vaccineSpike glycoproteinRecombinant proteinAdjuvantCoVaccine HT™Immunologic diseases. AllergyRC581-607ENVaccine: X, Vol 9, Iss , Pp 100126- (2021)
institution DOAJ
collection DOAJ
language EN
topic SARS-CoV-2 vaccine
Spike glycoprotein
Recombinant protein
Adjuvant
CoVaccine HT™
Immunologic diseases. Allergy
RC581-607
spellingShingle SARS-CoV-2 vaccine
Spike glycoprotein
Recombinant protein
Adjuvant
CoVaccine HT™
Immunologic diseases. Allergy
RC581-607
Chih-Yun Lai
Albert To
Teri Ann S. Wong
Michael M. Lieberman
David E. Clements
James T. Senda
Aquena H. Ball
Laurent Pessaint
Hanne Andersen
Wakako Furuyama
Andrea Marzi
Oreola Donini
Axel T. Lehrer
Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT™ adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice
description The speed at which several COVID-19 vaccines went from conception to receiving FDA and EMA approval for emergency use is an achievement unrivaled in the history of vaccine development. Mass vaccination efforts using the highly effective vaccines are currently underway to generate sufficient herd immunity and reduce transmission of the SARS-CoV-2 virus. Despite the most advanced vaccine technology, global recipient coverage, especially in resource-poor areas remains a challenge as genetic drift in naïve population pockets threatens overall vaccine efficacy. In this study, we described the production of insect-cell expressed SARS-CoV-2 spike protein ectodomain constructs and examined their immunogenicity in mice. We demonstrated that, when formulated with CoVaccine HTTM adjuvant, an oil-in-water nanoemulsion compatible with lyophilization, our vaccine candidates elicit a broad-spectrum IgG response, high neutralizing antibody (NtAb) titers against SARS-CoV-2 prototype and variants of concern, specifically B.1.351 (Beta) and P.1. (Gamma), and an antigen-specific IFN-γ secreting response in outbred mice. Of note, different ectodomain constructs yielded variations in NtAb titers against the prototype strain and some VOC. Dose response experiments indicated that NtAb titers increased with antigen dose, but not adjuvant dose, and may be higher with a lower adjuvant dose. Our findings lay the immunological foundation for the development of a dry-thermostabilized vaccine that is deployable without refrigeration.
format article
author Chih-Yun Lai
Albert To
Teri Ann S. Wong
Michael M. Lieberman
David E. Clements
James T. Senda
Aquena H. Ball
Laurent Pessaint
Hanne Andersen
Wakako Furuyama
Andrea Marzi
Oreola Donini
Axel T. Lehrer
author_facet Chih-Yun Lai
Albert To
Teri Ann S. Wong
Michael M. Lieberman
David E. Clements
James T. Senda
Aquena H. Ball
Laurent Pessaint
Hanne Andersen
Wakako Furuyama
Andrea Marzi
Oreola Donini
Axel T. Lehrer
author_sort Chih-Yun Lai
title Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT™ adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice
title_short Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT™ adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice
title_full Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT™ adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice
title_fullStr Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT™ adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice
title_full_unstemmed Recombinant protein subunit SARS-CoV-2 vaccines formulated with CoVaccine HT™ adjuvant induce broad, Th1 biased, humoral and cellular immune responses in mice
title_sort recombinant protein subunit sars-cov-2 vaccines formulated with covaccine ht™ adjuvant induce broad, th1 biased, humoral and cellular immune responses in mice
publisher Elsevier
publishDate 2021
url https://doaj.org/article/4899da1012804294873b875b8874ede5
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