Matrix M Adjuvanted H5N1 Vaccine Elicits Broadly Neutralizing Antibodies and Neuraminidase Inhibiting Antibodies in Humans That Correlate With In Vivo Protection

The highly pathogenic avian influenza H5N1 viruses constantly evolve and give rise to novel variants that have caused widespread zoonotic outbreaks and sporadic human infections. Therefore, vaccines capable of eliciting broadly protective antibody responses are desired and under development. We here...

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Autores principales:	Fan Zhou, Lena Hansen, Gabriel Pedersen, Gunnveig Grødeland, Rebecca Cox
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	H5N1 (Avian influenza) correlate of protection adjuvant Matrix M pseudotype neutralization neuraminidase inhibiting antibodies Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/40a683e824284aaa87ebeb97aee95c34
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spelling	oai:doaj.org-article:40a683e824284aaa87ebeb97aee95c342021-11-30T12:32:21ZMatrix M Adjuvanted H5N1 Vaccine Elicits Broadly Neutralizing Antibodies and Neuraminidase Inhibiting Antibodies in Humans That Correlate With In Vivo Protection1664-322410.3389/fimmu.2021.747774https://doaj.org/article/40a683e824284aaa87ebeb97aee95c342021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.747774/fullhttps://doaj.org/toc/1664-3224The highly pathogenic avian influenza H5N1 viruses constantly evolve and give rise to novel variants that have caused widespread zoonotic outbreaks and sporadic human infections. Therefore, vaccines capable of eliciting broadly protective antibody responses are desired and under development. We here investigated the magnitude, kinetics and protective efficacy of the multi-faceted humoral immunity induced by vaccination in healthy adult volunteers with a Matrix M adjuvanted virosomal H5N1 vaccine. Vaccinees were given escalating doses of adjuvanted vaccine (1.5μg, 7.5μg, or 30μg), or a non-adjuvanted vaccine (30μg). An evaluation of sera from vaccinees against pseudotyped viruses covering all (sub)clades isolated from human H5N1 infections demonstrated that the adjuvanted vaccines (7.5μg and 30μg) could elicit rapid and robust increases of broadly cross-neutralizing antibodies against all clades. In addition, the adjuvanted vaccines also induced multifaceted antibody responses including hemagglutinin stalk domain specific, neuraminidase inhibiting, and antibody-dependent cellular cytotoxicity inducing antibodies. The lower adjuvanted dose (1.5µg) showed delayed kinetics, whilst the non-adjuvanted vaccine induced overall lower levels of antibody responses. Importantly, we demonstrate that human sera post vaccination with the adjuvanted (30μg) vaccine provided full protection against a lethal homologous virus challenge in mice. Of note, when combining our data from mice and humans we identified the neutralizing and neuraminidase inhibiting antibody titers as correlates of in vivo protection.Fan ZhouLena HansenGabriel PedersenGabriel PedersenGunnveig GrødelandRebecca CoxRebecca CoxFrontiers Media S.A.articleH5N1 (Avian influenza)correlate of protectionadjuvantMatrix Mpseudotype neutralizationneuraminidase inhibiting antibodiesImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	H5N1 (Avian influenza) correlate of protection adjuvant Matrix M pseudotype neutralization neuraminidase inhibiting antibodies Immunologic diseases. Allergy RC581-607
spellingShingle	H5N1 (Avian influenza) correlate of protection adjuvant Matrix M pseudotype neutralization neuraminidase inhibiting antibodies Immunologic diseases. Allergy RC581-607 Fan Zhou Lena Hansen Gabriel Pedersen Gabriel Pedersen Gunnveig Grødeland Rebecca Cox Rebecca Cox Matrix M Adjuvanted H5N1 Vaccine Elicits Broadly Neutralizing Antibodies and Neuraminidase Inhibiting Antibodies in Humans That Correlate With In Vivo Protection
description	The highly pathogenic avian influenza H5N1 viruses constantly evolve and give rise to novel variants that have caused widespread zoonotic outbreaks and sporadic human infections. Therefore, vaccines capable of eliciting broadly protective antibody responses are desired and under development. We here investigated the magnitude, kinetics and protective efficacy of the multi-faceted humoral immunity induced by vaccination in healthy adult volunteers with a Matrix M adjuvanted virosomal H5N1 vaccine. Vaccinees were given escalating doses of adjuvanted vaccine (1.5μg, 7.5μg, or 30μg), or a non-adjuvanted vaccine (30μg). An evaluation of sera from vaccinees against pseudotyped viruses covering all (sub)clades isolated from human H5N1 infections demonstrated that the adjuvanted vaccines (7.5μg and 30μg) could elicit rapid and robust increases of broadly cross-neutralizing antibodies against all clades. In addition, the adjuvanted vaccines also induced multifaceted antibody responses including hemagglutinin stalk domain specific, neuraminidase inhibiting, and antibody-dependent cellular cytotoxicity inducing antibodies. The lower adjuvanted dose (1.5µg) showed delayed kinetics, whilst the non-adjuvanted vaccine induced overall lower levels of antibody responses. Importantly, we demonstrate that human sera post vaccination with the adjuvanted (30μg) vaccine provided full protection against a lethal homologous virus challenge in mice. Of note, when combining our data from mice and humans we identified the neutralizing and neuraminidase inhibiting antibody titers as correlates of in vivo protection.
format	article
author	Fan Zhou Lena Hansen Gabriel Pedersen Gabriel Pedersen Gunnveig Grødeland Rebecca Cox Rebecca Cox
author_facet	Fan Zhou Lena Hansen Gabriel Pedersen Gabriel Pedersen Gunnveig Grødeland Rebecca Cox Rebecca Cox
author_sort	Fan Zhou
title	Matrix M Adjuvanted H5N1 Vaccine Elicits Broadly Neutralizing Antibodies and Neuraminidase Inhibiting Antibodies in Humans That Correlate With In Vivo Protection
title_short	Matrix M Adjuvanted H5N1 Vaccine Elicits Broadly Neutralizing Antibodies and Neuraminidase Inhibiting Antibodies in Humans That Correlate With In Vivo Protection
title_full	Matrix M Adjuvanted H5N1 Vaccine Elicits Broadly Neutralizing Antibodies and Neuraminidase Inhibiting Antibodies in Humans That Correlate With In Vivo Protection
title_fullStr	Matrix M Adjuvanted H5N1 Vaccine Elicits Broadly Neutralizing Antibodies and Neuraminidase Inhibiting Antibodies in Humans That Correlate With In Vivo Protection
title_full_unstemmed	Matrix M Adjuvanted H5N1 Vaccine Elicits Broadly Neutralizing Antibodies and Neuraminidase Inhibiting Antibodies in Humans That Correlate With In Vivo Protection
title_sort	matrix m adjuvanted h5n1 vaccine elicits broadly neutralizing antibodies and neuraminidase inhibiting antibodies in humans that correlate with in vivo protection
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/40a683e824284aaa87ebeb97aee95c34
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Matrix M Adjuvanted H5N1 Vaccine Elicits Broadly Neutralizing Antibodies and Neuraminidase Inhibiting Antibodies in Humans That Correlate With In Vivo Protection

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