Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections

H5N1 COBRA hemagglutinin (HA) sequences, termed human COBRA-2 HA, were constructed through layering of HA sequences from viruses isolated from humans collected between 2004–2007 using only clade 2 strains. These COBRA HA proteins, when expressed on the surface of virus-like particles (VLP), elicited...

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Autores principales:	Ivette A. Nuñez, Ying Huang, Ted M. Ross
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	COBRA influenza H5N1 avian influenza vaccine H5Nx vaccine Medicine R
Acceso en línea:	https://doaj.org/article/f77127bfd75647069590b4e78ed1d0c3
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spelling	oai:doaj.org-article:f77127bfd75647069590b4e78ed1d0c32021-11-25T18:37:31ZNext-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections10.3390/pathogens101113522076-0817https://doaj.org/article/f77127bfd75647069590b4e78ed1d0c32021-10-01T00:00:00Zhttps://www.mdpi.com/2076-0817/10/11/1352https://doaj.org/toc/2076-0817H5N1 COBRA hemagglutinin (HA) sequences, termed human COBRA-2 HA, were constructed through layering of HA sequences from viruses isolated from humans collected between 2004–2007 using only clade 2 strains. These COBRA HA proteins, when expressed on the surface of virus-like particles (VLP), elicited protective immune responses in mice, ferrets, and non-human primates. However, these vaccines were not as effective at inducing neutralizing antibodies against newly circulating viruses. Therefore, COBRA HA-based vaccines were updated in order to elicit protective antibodies against the current circulating clades of H5Nx viruses. Next-generation COBRA HA vaccines were designed to encompass the newly emerging viruses circulating in wild avian populations. HA amino acid sequences from avian and human H5 influenza viruses isolated between 2011–2017 were downloaded from the GISAID (Global Initiative on Sharing All Influenza Data). Mice were vaccinated with H5 COBRA rHA that elicited antibodies with hemagglutinin inhibition (HAI) activity against H5Nx viruses from five clades. The H5 COBRA rHA vaccine, termed IAN8, elicited protective immune responses against mice challenged with A/Sichuan/26621/2014 and A/Vietnam/1203/2004. This vaccine elicited antibodies with HAI activity against viruses from clades 2.2, 2.3.2.1, 2.3.4.2, 2.2.1 and 2.2.2. Lungs from vaccinated mice had decreased viral titers and the levels of cellular infiltration in mice vaccinated with IAN-8 rHA were similar to mice vaccinated with wild-type HA comparator vaccines or mock vaccinated controls. Overall, these next-generation H5 COBRA HA vaccines elicited protective antibodies against both historical H5Nx influenza viruses, as well as currently circulating clades of H5N1, H5N6, and H5N8 influenza viruses.Ivette A. NuñezYing HuangTed M. RossMDPI AGarticleCOBRAinfluenzaH5N1avian influenza vaccineH5Nx vaccineMedicineRENPathogens, Vol 10, Iss 1352, p 1352 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COBRA influenza H5N1 avian influenza vaccine H5Nx vaccine Medicine R
spellingShingle	COBRA influenza H5N1 avian influenza vaccine H5Nx vaccine Medicine R Ivette A. Nuñez Ying Huang Ted M. Ross Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections
description	H5N1 COBRA hemagglutinin (HA) sequences, termed human COBRA-2 HA, were constructed through layering of HA sequences from viruses isolated from humans collected between 2004–2007 using only clade 2 strains. These COBRA HA proteins, when expressed on the surface of virus-like particles (VLP), elicited protective immune responses in mice, ferrets, and non-human primates. However, these vaccines were not as effective at inducing neutralizing antibodies against newly circulating viruses. Therefore, COBRA HA-based vaccines were updated in order to elicit protective antibodies against the current circulating clades of H5Nx viruses. Next-generation COBRA HA vaccines were designed to encompass the newly emerging viruses circulating in wild avian populations. HA amino acid sequences from avian and human H5 influenza viruses isolated between 2011–2017 were downloaded from the GISAID (Global Initiative on Sharing All Influenza Data). Mice were vaccinated with H5 COBRA rHA that elicited antibodies with hemagglutinin inhibition (HAI) activity against H5Nx viruses from five clades. The H5 COBRA rHA vaccine, termed IAN8, elicited protective immune responses against mice challenged with A/Sichuan/26621/2014 and A/Vietnam/1203/2004. This vaccine elicited antibodies with HAI activity against viruses from clades 2.2, 2.3.2.1, 2.3.4.2, 2.2.1 and 2.2.2. Lungs from vaccinated mice had decreased viral titers and the levels of cellular infiltration in mice vaccinated with IAN-8 rHA were similar to mice vaccinated with wild-type HA comparator vaccines or mock vaccinated controls. Overall, these next-generation H5 COBRA HA vaccines elicited protective antibodies against both historical H5Nx influenza viruses, as well as currently circulating clades of H5N1, H5N6, and H5N8 influenza viruses.
format	article
author	Ivette A. Nuñez Ying Huang Ted M. Ross
author_facet	Ivette A. Nuñez Ying Huang Ted M. Ross
author_sort	Ivette A. Nuñez
title	Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections
title_short	Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections
title_full	Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections
title_fullStr	Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections
title_full_unstemmed	Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections
title_sort	next-generation computationally designed influenza hemagglutinin vaccines protect against h5nx virus infections
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/f77127bfd75647069590b4e78ed1d0c3
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Next-Generation Computationally Designed Influenza Hemagglutinin Vaccines Protect against H5Nx Virus Infections

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