Live attenuated Listeria monocytogenes expressing HIV Gag: immunogenicity in rhesus monkeys.
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.
Jiang
Shisong
S
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Rasmussen
Robert A
RA
Nolan
Katrina M
KM
Frankel
Fred R
FR
Lieberman
Judy
J
McClure
Harold M
HM
Williams
Kristina M
KM
Babu
Uma S
US
Raybourne
Richard B
RB
Strobert
Elizabeth
E
Ruprecht
Ruth M
RM
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*
D016915:AIDS Vaccines; D015483:HIV Antibodies; D014613:Vaccines, Attenuated; D054301:gag Gene Products, Human Immunodeficiency Virus