Human immunodeficiency virus type 1 Gag-specific vaginal immunity and protection after local immunizations with sindbis virus-based replicon particles.
The majority of human immunodeficiency virus (HIV) infections occur through vaginal and rectal transmission. In seeking a safe, nonreplicating gene-delivery vector that can induce mucosal and systemic immune responses and protection, Sindbis virus-based replicon particles expressing HIV-1 Gag (SIN-Gag) were developed. In mice, after nasal or intramuscular immunization with SIN-Gag and vaginal challenge with vaccinia virus (VV) expressing HIV-1 Gag (VV-Gag), CD8(+) T cell-mediated responses were detected locally, in the vaginal mucosa and in the draining iliac lymph nodes (ILNs), and systemically, in the spleen. However, the mice were not protected against VV-Gag replication in the ovaries. In contrast, after vaginal or rectal immunization with SIN-Gag and vaginal challenge with VV-Gag, despite lower local CD8(+) T cell-mediated responses in the vaginal mucosa and ILNs, the mice were protected against VV-Gag replication in the ovaries. Therefore, local immunization with SIN-Gag induced both local mucosal cell-mediated responses and protection.
Vajdy
M
M
Chiron Corp., Immunology and Infectious Diseases, Emeryville, CA 94608, USA. michael _vajdy@chiron.com
Gardner
J
J
Neidleman
J
J
Cuadra
L
L
Greer
C
C
Perri
S
S
O'Hagan
D
D
Polo
J M
JM
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000818:Animals; D005260:Female; D015683:Gene Products, gag / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology; D018928:Immunity, Mucosal; D051379:Mice; D008807:Mice, Inbred BALB C; D010053:Ovary / Q000821:virology; D012093:Replicon; D012845:Sindbis Virus / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014621:Vagina / Q000276:immunology*; D014779:Virus Replication
D016915:AIDS Vaccines; D015683:Gene Products, gag; D019444:Vaccines, DNA