Vesicular Stomatitis Virus Chimeras Expressing the Oropouche Virus Glycoproteins Elicit Protective Immune Responses in Mice

ABSTRACT Oropouche virus (OROV) infection of humans is associated with a debilitating febrile illness that can progress to meningitis or encephalitis. First isolated from a forest worker in Trinidad and Tobago in 1955, the arbovirus OROV has since been detected throughout the Amazon basin with an es...

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Autores principales:	Sarah Hulsey Stubbs, Marjorie Cornejo Pontelli, Nischay Mishra, Changhong Zhou, Juliano de Paula Souza, Rosa Maria Mendes Viana, W. Ian Lipkin, David M. Knipe, Eurico Arruda, Sean P. J. Whelan
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	Oropouche virus arbovirus bunyavirus emerging infectious diseases vaccines Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/769e93f927cb42e19a1bbf60c6eef537
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spelling	oai:doaj.org-article:769e93f927cb42e19a1bbf60c6eef5372021-11-10T18:37:50ZVesicular Stomatitis Virus Chimeras Expressing the Oropouche Virus Glycoproteins Elicit Protective Immune Responses in Mice10.1128/mBio.00463-212150-7511https://doaj.org/article/769e93f927cb42e19a1bbf60c6eef5372021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00463-21https://doaj.org/toc/2150-7511ABSTRACT Oropouche virus (OROV) infection of humans is associated with a debilitating febrile illness that can progress to meningitis or encephalitis. First isolated from a forest worker in Trinidad and Tobago in 1955, the arbovirus OROV has since been detected throughout the Amazon basin with an estimated 500,000 human infections over 60 years. Like other members of the family Peribunyaviridae, the viral genome exists as 3 single-stranded negative-sense RNA segments. The medium-sized segment encodes a viral glycoprotein complex (GPC) that is proteolytically processed into two viral envelope proteins, Gn and Gc, responsible for attachment and membrane fusion. There are no therapeutics or vaccines to combat OROV infection, and we have little understanding of protective immunity to infection. Here, we generated a replication competent chimeric vesicular stomatitis virus (VSV), in which the endogenous glycoprotein was replaced by the GPC of OROV. Serum from mice immunized by intramuscular injection with VSV-OROV specifically neutralized wild-type OROV, and using peptide arrays we mapped multiple epitopes within an N-terminal variable region of Gc recognized by the immune sera. VSV-OROV lacking this variable region of Gc was also immunogenic in mice producing neutralizing sera that recognize additional regions of Gc. Challenge of both sets of immunized mice with wild-type OROV shows that the VSV-OROV chimeras reduce wild-type viral infection and suggest that antibodies that recognize the variable N terminus of Gc afford less protection than those that target more conserved regions of Gc. IMPORTANCE Oropouche virus (OROV), an orthobunyavirus found in Central and South America, is an emerging public health challenge that causes debilitating febrile illness. OROV is transmitted by arthropods, and increasing mobilization has the potential to significantly increase the spread of OROV globally. Despite this, no therapeutics or vaccines have been developed to combat infection. Using vesicular stomatitis (VSV) as a backbone, we developed a chimeric virus bearing the OROV glycoproteins (VSV-OROV) and tested its ability to elicit a neutralizing antibody response. Our results demonstrate that VSV-OROV produces a strong neutralizing antibody response that is at least partially targeted to the N-terminal region of Gc. Importantly, vaccination with VSV-OROV reduces viral loads in mice challenged with wild-type virus. These data provide novel evidence that targeting the OROV glycoproteins may be an effective vaccination strategy to combat OROV infection.Sarah Hulsey StubbsMarjorie Cornejo PontelliNischay MishraChanghong ZhouJuliano de Paula SouzaRosa Maria Mendes VianaW. Ian LipkinDavid M. KnipeEurico ArrudaSean P. J. WhelanAmerican Society for MicrobiologyarticleOropouche virusarbovirusbunyavirusemerging infectious diseasesvaccinesMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Oropouche virus arbovirus bunyavirus emerging infectious diseases vaccines Microbiology QR1-502
spellingShingle	Oropouche virus arbovirus bunyavirus emerging infectious diseases vaccines Microbiology QR1-502 Sarah Hulsey Stubbs Marjorie Cornejo Pontelli Nischay Mishra Changhong Zhou Juliano de Paula Souza Rosa Maria Mendes Viana W. Ian Lipkin David M. Knipe Eurico Arruda Sean P. J. Whelan Vesicular Stomatitis Virus Chimeras Expressing the Oropouche Virus Glycoproteins Elicit Protective Immune Responses in Mice
description	ABSTRACT Oropouche virus (OROV) infection of humans is associated with a debilitating febrile illness that can progress to meningitis or encephalitis. First isolated from a forest worker in Trinidad and Tobago in 1955, the arbovirus OROV has since been detected throughout the Amazon basin with an estimated 500,000 human infections over 60 years. Like other members of the family Peribunyaviridae, the viral genome exists as 3 single-stranded negative-sense RNA segments. The medium-sized segment encodes a viral glycoprotein complex (GPC) that is proteolytically processed into two viral envelope proteins, Gn and Gc, responsible for attachment and membrane fusion. There are no therapeutics or vaccines to combat OROV infection, and we have little understanding of protective immunity to infection. Here, we generated a replication competent chimeric vesicular stomatitis virus (VSV), in which the endogenous glycoprotein was replaced by the GPC of OROV. Serum from mice immunized by intramuscular injection with VSV-OROV specifically neutralized wild-type OROV, and using peptide arrays we mapped multiple epitopes within an N-terminal variable region of Gc recognized by the immune sera. VSV-OROV lacking this variable region of Gc was also immunogenic in mice producing neutralizing sera that recognize additional regions of Gc. Challenge of both sets of immunized mice with wild-type OROV shows that the VSV-OROV chimeras reduce wild-type viral infection and suggest that antibodies that recognize the variable N terminus of Gc afford less protection than those that target more conserved regions of Gc. IMPORTANCE Oropouche virus (OROV), an orthobunyavirus found in Central and South America, is an emerging public health challenge that causes debilitating febrile illness. OROV is transmitted by arthropods, and increasing mobilization has the potential to significantly increase the spread of OROV globally. Despite this, no therapeutics or vaccines have been developed to combat infection. Using vesicular stomatitis (VSV) as a backbone, we developed a chimeric virus bearing the OROV glycoproteins (VSV-OROV) and tested its ability to elicit a neutralizing antibody response. Our results demonstrate that VSV-OROV produces a strong neutralizing antibody response that is at least partially targeted to the N-terminal region of Gc. Importantly, vaccination with VSV-OROV reduces viral loads in mice challenged with wild-type virus. These data provide novel evidence that targeting the OROV glycoproteins may be an effective vaccination strategy to combat OROV infection.
format	article
author	Sarah Hulsey Stubbs Marjorie Cornejo Pontelli Nischay Mishra Changhong Zhou Juliano de Paula Souza Rosa Maria Mendes Viana W. Ian Lipkin David M. Knipe Eurico Arruda Sean P. J. Whelan
author_facet	Sarah Hulsey Stubbs Marjorie Cornejo Pontelli Nischay Mishra Changhong Zhou Juliano de Paula Souza Rosa Maria Mendes Viana W. Ian Lipkin David M. Knipe Eurico Arruda Sean P. J. Whelan
author_sort	Sarah Hulsey Stubbs
title	Vesicular Stomatitis Virus Chimeras Expressing the Oropouche Virus Glycoproteins Elicit Protective Immune Responses in Mice
title_short	Vesicular Stomatitis Virus Chimeras Expressing the Oropouche Virus Glycoproteins Elicit Protective Immune Responses in Mice
title_full	Vesicular Stomatitis Virus Chimeras Expressing the Oropouche Virus Glycoproteins Elicit Protective Immune Responses in Mice
title_fullStr	Vesicular Stomatitis Virus Chimeras Expressing the Oropouche Virus Glycoproteins Elicit Protective Immune Responses in Mice
title_full_unstemmed	Vesicular Stomatitis Virus Chimeras Expressing the Oropouche Virus Glycoproteins Elicit Protective Immune Responses in Mice
title_sort	vesicular stomatitis virus chimeras expressing the oropouche virus glycoproteins elicit protective immune responses in mice
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/769e93f927cb42e19a1bbf60c6eef537
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Vesicular Stomatitis Virus Chimeras Expressing the Oropouche Virus Glycoproteins Elicit Protective Immune Responses in Mice

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