title: Location and dynamics of the immunodominant CD8 T cell response to SIVΔnef immunization and SIVmac251 vaginal challenge.
abstract: Live-attenuated SIV vaccines (LAVs) have been the most effective to date in preventing or partially controlling infection by wild-type SIV in non-human primate models of HIV-1 transmission to women acting by mechanisms of protection that are not well understood. To gain insights into mechanisms of protection by LAVs that could aid development of effective vaccines to prevent HIV-1 transmission to women, we used in situ tetramer staining to determine whether increased densities or changes in the local distribution of SIV-specific CD8 T cells correlated with the maturation of SIVΔnef vaccine-induced protection prior to and after intra-vaginal challenge with wild-type SIVmac251. We evaluated the immunodominant Mamu-A1*001:01/Gag (CM9) and Mamu-A1*001:01/Tat (SL8) epitope response in genital and lymphoid tissues, and found that tetramer+ cells were present at all time points examined. In the cervical vaginal tissues, most tetramer+ cells were distributed diffusely throughout the lamina propria or co-localized with other CD8 T cells within lymphoid aggregates. The distribution and densities of the tetramer+ cells at the portal of entry did not correlate with the maturation of protection or change after challenge. Given these findings, we discuss the possibility that changes in other aspects of the immune system, including the quality of the resident population of virus-specific effector CD8 T cells could contribute to maturation of protection, as well as the potential for vaccine strategies that further increase the size and quality of this effector population to prevent HIV-1 transmission.
authors.affiliation: University of Minnesota, Veterinary and Biomedical Sciences Department, Saint Paul, Minnesota, United States of America.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Sasikala-Appukuttan
authors.affiliation: University of Minnesota, Veterinary and Biomedical Sciences Department, Saint Paul, Minnesota, United States of America.
authors.forename: Hyeon O
authors.initials: HO
authors.lastname: Kim
authors.affiliation: University of Minnesota, Veterinary and Biomedical Sciences Department, Saint Paul, Minnesota, United States of America.
authors.forename: Nikilyn J
authors.initials: NJ
authors.lastname: Kinzel
authors.affiliation: University of Minnesota, Veterinary and Biomedical Sciences Department, Saint Paul, Minnesota, United States of America.
authors.forename: Jung Joo
authors.initials: JJ
authors.lastname: Hong
authors.affiliation: University of Minnesota, Microbiology Department, Minneapolis, Minnesota, United States of America.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Smith
authors.affiliation: University of Minnesota, Veterinary and Biomedical Sciences Department, Saint Paul, Minnesota, United States of America.
authors.forename: Reece
authors.initials: R
authors.lastname: Wagstaff
authors.affiliation: University of Minnesota, School of Public Health, Division of Biostatistics, Minneapolis, Minnesota, United States of America.
authors.forename: Cavan
authors.initials: C
authors.lastname: Reilly
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., (formerly Science Applications International Corporation-Frederick, Inc.), Frederick National Laboratory, Frederick, Maryland, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., (formerly Science Applications International Corporation-Frederick, Inc.), Frederick National Laboratory, Frederick, Maryland, United States of America.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, United States of America.
authors.forename: R Keith
authors.initials: RK
authors.lastname: Reeves
authors.affiliation: Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, United States of America.
authors.forename: R Paul
authors.initials: RP
authors.lastname: Johnson
authors.affiliation: University of Minnesota, Microbiology Department, Minneapolis, Minnesota, United States of America.
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
authors.affiliation: University of Minnesota, Veterinary and Biomedical Sciences Department, Saint Paul, Minnesota, United States of America.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Skinner
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D007110:Immunity, Active / Q000187:drug effects; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology / Q000821:virology; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000187:drug effects* / Q000276:immunology; D014611:Vaccination; D014613:Vaccines, Attenuated; D014621:Vagina / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D019562:Viral Load / Q000187:drug effects; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; C429284:NEF protein, SIV; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated; D054334:Viral Regulatory and Accessory Proteins