Vaccine-elicited systemic and mucosal humoral responses of lactating rhesus monkeys vaccinated with the transmitted/founder HIV Envelope 1086C
© Fouda et al; licensee BioMed Central Ltd. 2012
Published: 13 September 2012
We previously demonstrated that vaccination of lactating rhesus monkeys with a DNA prime/ vector boost strategy induces strong SIV-specific cellular immune responses, but limited Envelope-specific humoral responses in breast milk. Therefore, we sought to improve vaccine-elicited Envelope-specific antibody responses in the milk compartment by using a transmitted/founder (T/F) HIV Envelope immunogen in a prime-boost strategy modeled after that of the moderately-successful RV144 HIV vaccine trial.
Eight female, hormone-induced lactating rhesus monkeys were intramuscularly primed with either recombinant DNA (n = 4) or MVA pox virus vector (n = 4) expressing the T/F clade C HIV Envelope 1086C. All animals were intramuscularly boosted twice with the 1086C gp120 protein and the adjuvant MF59. Milk, vaginal, rectal and plasma samples were assessed for HIV Envelope-binding IgG and IgA responses. Anti-V1V2 antibodies and neutralization responses were also measured in milk and plasma.
Envelope 1086C-binding IgG responses were detected in plasma, milk, and vaginal samples of all vaccinated animals and two of four rectal samples from MVA-vaccinated animals. Moreover, anti-V1V2 IgG antibodies were detected in all plasma, but only one milk sample. Low magnitude Envelope 1086C-specific IgA responses were detected in milk of two of four DNA-primed and three of four MVA-primed animals, but in none of the rectal samples. In contrast, all vaginal samples from MVA-primed, but none from DNA-primed, animals had detectable Envelope-specific IgA. Remarkably, strong tier 1 and low to moderate tier 2 neutralization was detected in plasma and milk of each group. The plasma neutralization titers against MW965 (clade C tier 1, p=0.03) and CAP45 (clade C tier 2, p=0.03) were significantly higher in MVA-primed than DNA-primed animals.
MVA prime/ T/F Envelope protein boost strategy appears to induce stronger systemic and mucosal binding and neutralizing antibody responses than the DNA prime/protein boost regimen in lactating rhesus monkeys.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.