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J Immunol. 2017 Sep 1;199(5):1923-1932. doi: 10.4049/jimmunol.1700320. Epub 2017 Jul 31.

Modified Vaccinia Virus Ankara Vector Induces Specific Cellular and Humoral Responses in the Female Reproductive Tract, the Main HIV Portal of Entry.

Author information

1
Immunologie des Infections Virales et des Maladies Auto-immunes (ImVA)/Infrastructure Nationale pour la Modélisation des Maladies Infectieuses Humaines et les Thérapies Innovantes (IDMIT)/Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA)/Direction de la Recherche Fondamentale (DRF)/Institut des Maladies Emergentes et des Traitements Innovants (IMETI), Université Paris-Sud, INSERM U1184, 92265 Fontenay-Aux-Roses, France.
2
Mucosal Innate Immunity and Sexually Transmitted Infections Control Group, Department of Virology, Institut Pasteur, 75015 Paris, France.
3
Vaccine Research Institute, Henri Mondor Hospital, 94010 Créteil, France.
4
Faculté de Médecine, Université Paris-Est, INSERM U955, 94010 Créteil, France.
5
Service d'Immunologie Clinique, Groupe Henri-Mondor Albert-Chenevier, Assistance Publique-Hôpitaux de Paris, 94010 Créteil, France.
6
Division Internationale, Institut Pasteur, 75015 Paris, France; and.
7
Viral Evolution and Transmission Unit, San Raffaele Scientific Institute, 20132 Milan, Italy.
8
Immunologie des Infections Virales et des Maladies Auto-immunes (ImVA)/Infrastructure Nationale pour la Modélisation des Maladies Infectieuses Humaines et les Thérapies Innovantes (IDMIT)/Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA)/Direction de la Recherche Fondamentale (DRF)/Institut des Maladies Emergentes et des Traitements Innovants (IMETI), Université Paris-Sud, INSERM U1184, 92265 Fontenay-Aux-Roses, France; elisabeth.menu@pasteur.fr.

Abstract

The female reproductive tract (FRT) is one of the major mucosal invasion sites for HIV-1. This site has been neglected in previous HIV-1 vaccine studies. Immune responses in the FRT after systemic vaccination remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized specific immune responses in all compartments of the FRT of nonhuman primates after systemic vaccination. Memory T cells were preferentially found in the lower tract (vagina and cervix), whereas APCs and innate lymphoid cells were mainly located in the upper tract (uterus and fallopian tubes). This compartmentalization of immune cells in the FRT was supported by transcriptomic analyses and a correlation network. Polyfunctional MVA-specific CD8+ T cells were detected in the blood, lymph nodes, vagina, cervix, uterus, and fallopian tubes. Anti-MVA IgG and IgA were detected in cervicovaginal fluid after a second vaccine dose. Thus, systemic vaccination with an MVA vector elicits cellular and Ab responses in the FRT.

PMID:
28760882
DOI:
10.4049/jimmunol.1700320
[Indexed for MEDLINE]
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