title: A single vaccination with attenuated SIVmac 239 via the tonsillar route confers partial protection against challenge with SIVmac 251 at a distant mucosal site, the rectum.
abstract: Elucidating the mechanisms that protect monkeys previously immunized with attenuated SIV (SIVDeltanef) against challenge infection with pathogenic virus may reveal new strategies for the development of an effective HIV vaccine. Here we show that a single atraumatic application of SIVDeltanef to the tonsils of four rhesus macaques conferred protection against SIVmac251 applied intrarectally 26 weeks later. While this protection was not complete, i.e., challenge virus could be isolated from all immunized animals, it was reflected by significantly lower viral loads in the blood (weeks 2-16 after challenge, p < 0.01) and considerably lower loads in lymphoid organs, and more stable peripheral CD4 counts in a proportion of the immunized animals as compared to four non-immunized, SIVmac251-infected control monkeys. SIV-specific humoral as well as systemic and mucosal T cell responses were detected in the immunized animals, but there was no correlation between their magnitude of expression and the level of protection. Analyses of leukocyte subsets in these animals at necropsy (24 weeks after challenge) did not reveal a significantly enhanced proportion of gamma/delta T cells in the tissues of protected monkeys. Therefore, tonsillar application of attenuated SIV induces protection in some animals against a superinfection with wild-type SIV distant at a distant mucosal site.
authors.affiliation: German Primate Center, D-37077 Göttingen, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Stahl-Hennig
authors.forename: Martin
authors.initials: M
authors.lastname: Eisenblatter
authors.forename: Monika
authors.initials: M
authors.lastname: Franz
authors.forename: Heribert
authors.initials: H
authors.lastname: Stoiber
authors.forename: Klara
authors.initials: K
authors.lastname: Tenner-Racz
authors.forename: You-Suk
authors.initials: YS
authors.lastname: Suh
authors.forename: Edith
authors.initials: E
authors.lastname: Jasny
authors.forename: Barbara
authors.initials: B
authors.lastname: Falkensammer
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Ugucchioni
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Georgsson
authors.forename: Carlo
authors.initials: C
authors.lastname: Baroni
authors.forename: Manfred P
authors.initials: MP
authors.lastname: Dierich
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Steinman
authors.forename: Klaus
authors.initials: K
authors.lastname: Uberla
authors.forename: Paul
authors.initials: P
authors.lastname: Racz
authors.forename: Ralf
authors.initials: R
authors.lastname: Ignatius
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D017353:Gene Deletion; D015754:Genes, nef; D007111:Immunity, Cellular; D007413:Intestinal Mucosa / Q000276:immunology / Q000821:virology; D008198:Lymph Nodes / Q000821:virology; D008253:Macaca mulatta; D008297:Male; D014066:Palatine Tonsil / Q000821:virology; D012367:RNA, Viral / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D012007:Rectum / Q000821:virology; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D012367:RNA, Viral; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated