Dr. Grazia Ferrari Presented at the AIDS Vaccine 2010
Prime-boost vaccination via parental and mucosal routes induces systemic and mucosal immunity and control of plasma viremia following heterologous SHIV challenge
Maria Grazia Ferrari1, Ranajit Pal1, Britany Bowen1, DeVon Thompson1, Lauren Hudacik1, Eun Mi Lee1,Lindsey Galmin1, Brad Lewis1, Deborah Weiss1, Linda Wyatt2, Pat Earl2,
Anthony Cristillo1, Vaniambadi Kalyanaraman1, Philip Markham1 and Thomas VanCott1
1Advanced BioScience Laboratories, Inc. Kensington, Maryland; 2NIAID, National Institutes of Health, Bethesda, Maryland
Background: As sexual transmission of HIV-1 occurs via the mucosal route, an effective HIV-1 vaccine should induce both mucosal and systemic immunity. Although partial success of RV144 trial underscores the importance of prime/boost vaccine regimen for containment of HIV infection, induction of mucosal immunity was not focused in this trial. Therefore immunogenicity and efficacy of prime/boost vaccine designed to induce both systemic and mucosal immunity warrants further investigation.
Methods: A heterologous prime-boost vaccine regimen utilizing DNA encoding HIV-1Ba-L env and SIV gag, MVA encoding HIV-1ADA env and SIV gag/pol genes, and a mixture of adjuvanted-gp120 from 5 different clades was tested in rhesus macaques. Group 1 macaques received two DNA immunizations via electroporation, followed by two immunizations intramuscularly with MVA and gp120 protein adjuvanted with QS-21; Group 2 received two DNA immunizations via electroporation and intranasally adjuvanted by polyethylenimine, followed by two immunizations where MVA was administered intranasally and HIV-1 gp120 protein was administered intramuscularly (both adjuvanted by polyethylenimine). Immunizations were administered at week 0 and 8 (DNA) and week 20 and 29 (MVA+protein). Antibodies and T-cells responses were measured at systemic and mucosal compartments. Macaques were challenged intrarectally with heterologous SHIV162P4 at week 33 and the challenge outcome was monitored by quantitation of plasma viral RNA load.
Results: All vaccinated macaques developed gp120-specific serum IgG and IgA responses. T-cell specific responses were detected in PBMCs by IFN-g ELISPOT and cytokine multiplexing. Further Intracellular Cytokine Staining revealed CD8+ and CD4+ responses in lymphocytes from bronchoalveolar lavages, jejunum and rectal pinch biopsies. Following challenge one animal from group 1 was completely protected while other immunized animals were infected and showed a significant control of viremia compared to the naïve controls.
Conclusion: Prime/boost vaccine regimen inducing antibody and cellular immune responses in systemic and mucosal compartments provides partial protection against heterologous mucosal challenge.
