title: Live simian immunodeficiency virus vaccine correlate of protection: local antibody production and concentration on the path of virus entry.
abstract: We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium. This local Ab production and delivery system correlated spatially and temporally with the maturation of local protection against high-dose pathogenic SIV vaginal challenge. Thus, designing vaccines to elicit production and concentration of Abs at mucosal frontlines could aid in the development of an effective vaccine to protect women against HIV-1.
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Ming
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Lijie
authors.initials: L
authors.lastname: Duan
authors.affiliation: Department of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center, and Center for HIV/AIDS Vaccine Immunology and Immunogen Design, The Scripps Research Institute, La Jolla, CA 92037; Ragon Institute of MGH, MIT, and Harvard, Charlestown, MA 02129;
authors.forename: James E
authors.initials: JE
authors.lastname: Voss
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Smith
authors.affiliation: Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Stefan
authors.initials: S
authors.lastname: Pambuccian
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Liang
authors.initials: L
authors.lastname: Shang
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Stephen
authors.initials: S
authors.lastname: Wietgrefe
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Southern
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Cavan S
authors.initials: CS
authors.lastname: Reilly
authors.affiliation: Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108;
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Skinner
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Mary L
authors.initials: ML
authors.lastname: Zupancic
authors.affiliation: Department of Computer Science and Engineering, College of Science and Engineering, University of Minnesota, Minneapolis, MN 55455;
authors.forename: John V
authors.initials: JV
authors.lastname: Carlis
authors.affiliation: AIDS and Cancer Virus Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, MD 21702;
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.affiliation: ZeptoMetrix Corporation, Buffalo, NY 14202;
authors.forename: Diane
authors.initials: D
authors.lastname: Waterman
authors.affiliation: New England Primate Research Center, Harvard Medical School, Southborough, MA 01772; Infectious Disease Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02115;
authors.forename: R Keith
authors.initials: RK
authors.lastname: Reeves
authors.affiliation: New England Primate Research Center, Harvard Medical School, Southborough, MA 01772; Infectious Disease Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA 02115;
authors.forename: Katherine
authors.initials: K
authors.lastname: Masek-Hammerman
authors.affiliation: Department of Pathology and Laboratory Medicine and Emory Vaccine Center, Emory University, Yerkes, Atlanta, GA 30329;
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Derdeyn
authors.affiliation: New England Primate Research Center, Harvard Medical School, Southborough, MA 01772; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115;
authors.forename: Michael D
authors.initials: MD
authors.lastname: Alpert
authors.affiliation: New England Primate Research Center, Harvard Medical School, Southborough, MA 01772; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115;
authors.forename: David T
authors.initials: DT
authors.lastname: Evans
authors.affiliation: Department of Microbiology and Immunology and Molecular Genetics, University of Kentucky, Lexington, KY 40536;
authors.forename: Heinz
authors.initials: H
authors.lastname: Kohler
authors.affiliation: ImmPheron Inc., Lexington, KY 40509; and.
authors.forename: Sybille
authors.initials: S
authors.lastname: Müller
authors.affiliation: Department of Pediatrics, Center for Infectious Diseases, Tulane University, New Orleans, LA 70112.
authors.forename: James
authors.initials: J
authors.lastname: Robinson
authors.affiliation: AIDS and Cancer Virus Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, MD 21702;
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: Department of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center, and Center for HIV/AIDS Vaccine Immunology and Immunogen Design, The Scripps Research Institute, La Jolla, CA 92037; Ragon Institute of MGH, MIT, and Harvard, Charlestown, MA 02129;
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Charlestown, MA 02129; New England Primate Research Center, Harvard Medical School, Southborough, MA 01772;
authors.forename: R Paul
authors.initials: RP
authors.lastname: Johnson
authors.affiliation: Department of Microbiology, Medical School, University of Minnesota, Minneapolis, MN 55455; haase001@umn.edu.
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D002584:Cervix Uteri / Q000276:immunology* / Q000821:virology; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000276:immunology; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D014621:Vagina / Q000276:immunology* / Q000821:virology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015700:HIV Envelope Protein gp41; D007074:Immunoglobulin G; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated