Systemic and Mucosal Immunity Is Elicited after Both Intramuscular and Intravaginal Delivery of Human Immunodeficiency Virus Type 1 DNA Plasmid Vaccines to Pregnant Chimpanzees

Abstract

DNA vaccines encoding human immunodeficiency virus type 1 (HIV-1) env/rev and gag/pol were delivered intravaginally (IVAG) and intramuscularly (IM) to 2 pregnant chimpanzees. Vaccination was well tolerated and each chimpanzee developed antibodies (up to 1 year later) to both vaccines. Placental transfer of anti-Env and anti-Gag IgG was demonstrated in both maternal/infant pairs. Specific IgG was also demonstrated in saliva, vaginal, and rectal washes after IVAG immunization. Predominantly anti-HIV-1 IgA was detected in the milk of both mothers after both IM and IVAG immunization. Cellular responses included Gag-specific proliferation of lymphocytes and cytotoxic T lymphocytes against both antigens. These data suggest a strategy for induction of mucosal and systemic responses after both IM and IVAG delivery of DNA vaccines in a primate model and could ultimately be useful in lowering maternal-to-fetal transmission of HIV-1, perinatally and through breastfeeding.

Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo

“…RNA was eluted in water and RNA concentrations were measured by spectrophotometry. Reverse transcriptase-PCR was performed using the First Strand cDNA Synthesis Kit (Invitrogen, Carlsbad, CA, USA) using oligo dt (12)(13)(14)(15)(16)(17)(18) primers and superscript II to generate cDNA strands (Invitrogen). For PCR, the sense primer used for amplification of wild-type CCR10 was designed and carried out as described by Morteau et al 37 Briefly, primers are specific for the region upstream from the site of insertion of the targeting construct (ATG codon): 5 0 -CGGAGAA ACCCTTGTAGCCAG-3 0 .…”

“…1,[7][8][9][10][11] The inclusion of genes encoding cytokines or chemokines (immune trafficking signals) in a vaccination strategy can alter the magnitude, duration and nature of the immune response and such genes have been tested as vaccine adjuvants. [12][13][14][15][16][17] These strategies have shown promise in improving the efficacy of DNA vaccines in large-animal models such as horses, dogs and pigs, as well as in humans. 2,[18][19][20][21][22] Currently, several DNAbased veterinary products have been licensed for use.…”

Vaccine-Induced Immune Responses in Rodents and Nonhuman Primates by Use of a Humanized Human Immunodeficiency Virus Type 1 pol Gene

“…However, there is no convincing evidence for a strong vaccine-induced T-cell immunity against Pol when using these constructs. In the only work directly related to HIV-1 Pol, chimpanzees were treated with DNA vaccines for HIV-1 gag-pol fusion products (1,6). Bulk-culture proliferative and CTL activities were observed on stimulation with gag-polexpressing poxviruses, but the extent to which these responses are directed at pol remains unclear.…”

“…Cellular immunity can be induced using a number of in vivo gene-based transfection approaches that include nonintegrating DNA plasmids (1,2,6,44) and replication-defective viral vectors (3,7,9,13,22). Reports on vaccine-induced cellular immunity against Pol in model animal systems have, however, been limited (25).…”

“…Reports on vaccine-induced cellular immunity against Pol in model animal systems have, however, been limited (25). While nonhuman primate studies that involve immunization with DNA vaccines consisting of HIV-1 Pol have been reported (1,6), there has been no definitive evidence that a cellular immune response to this antigen has been generated in these animal systems. The usefulness of rodent systems in assessing the immunogenicity of vaccine candidates is even more limited given that only one CTL epitope (in C3H, H-2 k background) (24) is known to date.…”