title: Mucosal Humoral Immune Response to SIVmac239∆nef Vaccination and Vaginal Challenge.
abstract: Live attenuated vaccines such as SIV with a deleted nef gene have provided the most robust protection against subsequent vaginal challenge with wild-type (WT) SIV in the SIV-rhesus macaque model of HIV-1 transmission to women. Hence, identifying correlates of this protection could enable design of an effective HIV-1 vaccine. One such prechallenge correlate of protection from vaginal challenge has recently been identified as a system with three components: 1) IgG Abs reacting with the viral envelope glycoprotein trimeric gp41; 2) produced by plasma cells in the submucosa and ectopic tertiary lymphoid follicles in the ectocervix and vagina; and 3) concentrated on the path of virus entry by the neonatal FcR in the overlying epithelium. We now examine the mucosal production of the Ab component of this system after vaginal challenge. We show that vaginal challenge immediately elicits striking increases in plasma cells not only in the female reproductive tract but also at other mucosal sites, and that these increases correlate with low but persistent replication at mucosal sites. We describe vaginal ectopic follicles that are structurally and functionally organized similar to follicles in secondary lymphoid organs, and we provide inferential evidence for a key role of the female reproductive tract epithelium in facilitating Ab production, affinity maturation, and class switch recombination. Vaccination thus accesses an epithelial-immune system axis in the female reproductive tract to respond to exposure to mucosal pathogens. Designing strategies to mimic this system could advance development of an effective HIV-1 vaccine.
authors: Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors: Ming
authors: M
authors: Zeng
authors: Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors: Anthony J
authors: AJ
authors: Smith
authors: Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors: Liang
authors: L
authors: Shang
authors: Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors: Stephen W
authors: SW
authors: Wietgrefe
authors: Department of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunology and Immunogen Design, The Scripps Research Institute, La Jolla, CA 92037;
authors: James E
authors: JE
authors: Voss
authors: Department of Computer Science and Engineering, College of Science and Engineering, University of Minnesota, Minneapolis, MN 55455;
authors: John V
authors: JV
authors: Carlis
authors: Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors: Qingsheng
authors: Q
authors: Li
authors: AIDS and Cancer Virus Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, MD 21702;
authors: Michael
authors: M
authors: Piatak
authors: AIDS and Cancer Virus Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, MD 21702;
authors: Jeffrey D
authors: JD
authors: Lifson
authors: New England Primate Research Center, Harvard Medical School, Southborough, MA, 01772; and Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139.
authors: R Paul
authors: RP
authors: Johnson
authors: Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, MN 55455; haase001@umn.edu.
authors: Ashley T
authors: AT
authors: Haase
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D004848:Epithelium / Q000276:immunology / Q000378:metabolism*; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007114:Immunization; D008253:Macaca mulatta; D011961:Receptors, Fc / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000502:physiology*; D014613:Vaccines, Attenuated; D014621:Vagina / Q000276:immunology*; D053586:Virus Internalization; D014779:Virus Replication
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015700:HIV Envelope Protein gp41; D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; D014613:Vaccines, Attenuated; C100688:Fc receptor, neonatal