title: Simian-human immunodeficiency virus SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239 is independent of the route of immunization and is associated with a combination of cytotoxic T-lymphocyte and alpha interferon responses.
abstract: Attenuated primate lentivirus vaccines provide the most consistent protection against challenge with pathogenic simian immunodeficiency virus (SIV). Thus, they provide an excellent model to examine the influence of the route of immunization on challenge outcome and to study vaccine-induced protective anti-SIV immune responses. In the present study, rhesus macaques were immunized with live nonpathogenic simian-human immunodeficiency virus (SHIV) 89.6 either intravenously or mucosally (intranasally or intravaginally) and then challenged intravaginally with pathogenic SIVmac239. The route of immunization did not affect mucosal challenge outcome after a prolonged period of systemic infection with the nonpathogenic vaccine virus. Further, protection from the SIV challenge was associated with the induction of multiple host immune effector mechanisms. A comparison of immune responses in vaccinated-protected and vaccinated-unprotected animals revealed that vaccinated-protected animals had higher frequencies of SIV Gag-specific cytotoxic T lymphocytes and gamma interferon (IFN-gamma)-secreting cells during the acute phase postchallenge. Vaccinated-protected animals also had a more pronounced increase in peripheral blood mononuclear cell IFN-alpha mRNA levels than did the vaccinated-unprotected animals in the first few weeks after challenge. Thus, innate as well as cellular anti-SIV immune responses appeared to contribute to the SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239.
authors.affiliation: Center for Comparative Medicine, California National Primate Research Center, School of Veterinary Medicine, University of California-Davis, California 95616, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Abel
authors.forename: Lara
authors.initials: L
authors.lastname: Compton
authors.forename: Tracy
authors.initials: T
authors.lastname: Rourke
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Ding
authors.initials: D
authors.lastname: Lu
authors.forename: Kristina
authors.initials: K
authors.lastname: Rothaeusler
authors.forename: Linda
authors.initials: L
authors.lastname: Fritts
authors.forename: Kristen
authors.initials: K
authors.lastname: Bost
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Miller
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D018791:CD4 Lymphocyte Count; D005260:Female; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D012367:RNA, Viral / Q000097:blood; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology / Q000472:pathogenicity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D014613:Vaccines, Attenuated; D014621:Vagina / Q000821:virology
chemical_list: D000914:Antibodies, Viral; D016898:Interferon-alpha; D012367:RNA, Viral; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated