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...
Guardado en:
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | article |
Lenguaje: | EN |
Publicado: |
Elsevier
2021
|
Materias: | |
Acceso en línea: | https://doaj.org/article/4899da1012804294873b875b8874ede5 |
Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
id |
oai:doaj.org-article:4899da1012804294873b875b8874ede5 |
---|---|
record_format |
dspace |
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 |
work_keys_str_mv |
AT chihyunlai recombinantproteinsubunitsarscov2vaccinesformulatedwithcovaccinehtadjuvantinducebroadth1biasedhumoralandcellularimmuneresponsesinmice AT albertto recombinantproteinsubunitsarscov2vaccinesformulatedwithcovaccinehtadjuvantinducebroadth1biasedhumoralandcellularimmuneresponsesinmice AT teriannswong recombinantproteinsubunitsarscov2vaccinesformulatedwithcovaccinehtadjuvantinducebroadth1biasedhumoralandcellularimmuneresponsesinmice AT michaelmlieberman recombinantproteinsubunitsarscov2vaccinesformulatedwithcovaccinehtadjuvantinducebroadth1biasedhumoralandcellularimmuneresponsesinmice AT davideclements recombinantproteinsubunitsarscov2vaccinesformulatedwithcovaccinehtadjuvantinducebroadth1biasedhumoralandcellularimmuneresponsesinmice AT jamestsenda recombinantproteinsubunitsarscov2vaccinesformulatedwithcovaccinehtadjuvantinducebroadth1biasedhumoralandcellularimmuneresponsesinmice AT aquenahball recombinantproteinsubunitsarscov2vaccinesformulatedwithcovaccinehtadjuvantinducebroadth1biasedhumoralandcellularimmuneresponsesinmice AT laurentpessaint recombinantproteinsubunitsarscov2vaccinesformulatedwithcovaccinehtadjuvantinducebroadth1biasedhumoralandcellularimmuneresponsesinmice AT hanneandersen recombinantproteinsubunitsarscov2vaccinesformulatedwithcovaccinehtadjuvantinducebroadth1biasedhumoralandcellularimmuneresponsesinmice AT wakakofuruyama recombinantproteinsubunitsarscov2vaccinesformulatedwithcovaccinehtadjuvantinducebroadth1biasedhumoralandcellularimmuneresponsesinmice AT andreamarzi recombinantproteinsubunitsarscov2vaccinesformulatedwithcovaccinehtadjuvantinducebroadth1biasedhumoralandcellularimmuneresponsesinmice AT oreoladonini recombinantproteinsubunitsarscov2vaccinesformulatedwithcovaccinehtadjuvantinducebroadth1biasedhumoralandcellularimmuneresponsesinmice AT axeltlehrer recombinantproteinsubunitsarscov2vaccinesformulatedwithcovaccinehtadjuvantinducebroadth1biasedhumoralandcellularimmuneresponsesinmice |
_version_ |
1718409839068053504 |