title: Comparison of systemic and mucosal immunization with helper-dependent adenoviruses for vaccination against mucosal challenge with SHIV.
abstract: Most HIV-1 infections are thought to occur at mucosal surfaces during sexual contact. It has been hypothesized that vaccines delivered at mucosal surfaces may mediate better protection against HIV-1 than vaccines that are delivered systemically. To test this, rhesus macaques were vaccinated by intramuscular (i.m.) or intravaginal (ivag.) routes with helper-dependent adenoviral (HD-Ad) vectors expressing HIV-1 envelope. Macaques were first immunized intranasally with species C Ad serotype 5 (Ad5) prior to serotype-switching with species C HD-Ad6, Ad1, Ad5, and Ad2 vectors expressing env followed by rectal challenge with CCR5-tropic SHIV-SF162P3. Vaccination by the systemic route generated stronger systemic CD8 T cell responses in PBMC, but weaker mucosal responses. Conversely, mucosal immunization generated stronger CD4 T cell central memory (Tcm) responses in the colon. Intramuscular immunization generated higher levels of env-binding antibodies, but neither produced neutralizing or cytotoxic antibodies. After mucosal SHIV challenge, both groups controlled SHIV better than control animals. However, more animals in the ivag. group had lower viral set points than in in the i.m. group. These data suggest mucosal vaccination may have improve protection against sexually-transmitted HIV. These data also demonstrate that helper-dependent Ad vaccines can mediate robust vaccine responses in the face of prior immunity to Ad5 and during four rounds of adenovirus vaccination.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Translational Immunovirology Program, Department of Immunology, Mayo Clinic, Rochester, Minnesota, United States of America.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Weaver
authors.forename: Pramod N
authors.initials: PN
authors.lastname: Nehete
authors.forename: Bharti P
authors.initials: BP
authors.lastname: Nehete
authors.forename: Guojun
authors.initials: G
authors.lastname: Yang
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Buchl
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Hanley
authors.forename: Donna
authors.initials: D
authors.lastname: Palmer
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Philip
authors.initials: P
authors.lastname: Ng
authors.forename: K Jagannadha
authors.initials: KJ
authors.lastname: Sastry
authors.forename: Michael A
authors.initials: MA
authors.lastname: Barry
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D006378:Helper Viruses / Q000235:genetics; D007109:Immunity; D018928:Immunity, Mucosal; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000276:immunology / Q000821:virology; D054353:Perforin / Q000096:biosynthesis; D019713:Receptors, CCR5 / Q000378:metabolism; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D014621:Vagina / Q000821:virology; D056189:Viral Tropism / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D019713:Receptors, CCR5; D018449:SAIDS Vaccines; D054353:Perforin; D007371:Interferon-gamma