title: Live attenuated Listeria monocytogenes expressing HIV Gag: immunogenicity in rhesus monkeys.
abstract: Induction of strong cellular immunity will be important for AIDS vaccine candidates. Natural infection with wild-type Listeria monocytogenes (Lm), an orally transmitted organism, is known to generate strong cellular immunity, thus raising the possibility that live attenuated Lm could serve as a vaccine vector. We sought to examine the potential of live attenuated Lm to induce cellular immune responses to HIV Gag. Rhesus macaques were immunized with Lmdd-gag that expresses HIV gag and lacks two genes in the D-alanine (D-ala) synthesis pathway. Without this key component of the bacterial cell wall, vaccine vector replication critically depends on exogenous D-ala. Lmdd-gag was given to animals either solely orally or by oral priming followed by intramuscular (i.m.) boosting; D-ala was co-administered with all vaccinations. Lmdd-gag and D-ala were well tolerated. Oral priming/oral boosting induced Gag-specific cellular immune responses, whereas oral priming/i.m. boosting induced systemic as well as mucosal anti-Gag antibodies. These results suggest that the route of vaccination may bias anti-Gag immune responses either towards T-helper type 1 (Th1) or Th2 responses; overall, our data show that live attenuated, recombinant Lmdd-gag is safe and immunogenic in primates.
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Shisong
authors.initials: S
authors.lastname: Jiang
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rasmussen
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Nolan
authors.forename: Fred R
authors.initials: FR
authors.lastname: Frankel
authors.forename: Judy
authors.initials: J
authors.lastname: Lieberman
authors.forename: Harold M
authors.initials: HM
authors.lastname: McClure
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Williams
authors.forename: Uma S
authors.initials: US
authors.lastname: Babu
authors.forename: Richard B
authors.initials: RB
authors.lastname: Raybourne
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Strobert
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Ruprecht
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*; D000284:Administration, Oral; D000818:Animals; D017353:Gene Deletion; D005798:Genes, Bacterial; D015750:Genes, gag; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D008089:Listeria monocytogenes / Q000235:genetics* / Q000276:immunology*; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D012449:Safety; D013601:T-Lymphocytes / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D015483:HIV Antibodies; D014613:Vaccines, Attenuated; D054301:gag Gene Products, Human Immunodeficiency Virus