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Background:  Vaccinia viruses were highly effective in the eradication of smallpox, but they are associated with rare, but severe side effects, particularly for immune compromised individuals. To improve the safety of smallpox vaccines, attenuated vaccinia vectors have been developed. MVA is a highly attenuated vaccinia virus that replicates poorly, if at all, in mammalian cells. So far, data are lacking regarding the immunogenicity of MVA in HIV-1-infected patients. Therefore, we analyzed both in HIV-1-infected patients and in healthy subjects the induction of MVA-specific antibodies and T cells after immunization with a recombinant HIV-1 nef-expressing MVA.

Methods:  We vaccinated subcutaneously, 14 HIV-1-infected patients on HAART and 14 HIV-negative subjects with MVA-nef at a dosage of 5 x 10⁸ TCID₅₀ at weeks 0, 4, and 16. All 14 HIV⁺ and 4 of 14 HIV^– subjects had received smallpox vaccination in their childhood, whereas 10 of 14 HIV^– subjects were vaccinia naive. MVA-specific T cells were monitored by interferon-γ ELISpot and MVA-specific antibodies by ELISA.

Results:  At baseline, MVA-specific T cells could be detected in 3 patients (120 to 180 SFU/10⁶ PBMC) and in 2 HIV^– subjects (70 and 100 SFU/10⁶ PBMC). All subjects developed an MVA-specific T-cell response 2 to 4 weeks after the third vaccination. At week 4, 6, and 16, but not at week 18, the median frequencies of MVA-specific T cells in HIV^– subjects were significantly higher than in the HIV⁺ patients. The median frequency of MVA-specific T cells at week 18 was 860 SFU/10⁶ PBMC (range 260 to 3330) in HIV^–subjects and 490 SFU/10⁶ PBMC (range 30 to 4360) in the HIV⁺ patients. Depletion experiments performed in 8 patients and in all HIV^– subjects revealed that in 6 of 8 HIV⁺ patients and in 4 of 14 HIV^– subjects MVA was recognized only by CD8⁺ T cells, while in 2 of 8 patients and in 10 of 14 HIV^–subjects both MVA-specific CD4⁺ T cells and CD8⁺ T cells could be detected. Prior to vaccination, 5 of 14 HIV⁺ subjects and 4 of 14 HIV^– subjects had a weak antibody response to MVA. By 4 weeks after a single immunization, 13 of 14 infected individuals developed MVA-specific antibodies while the remaining patient seroconverted following the second vaccination. All 14 controls seroconverted at week 4.

Conclusions:  This study demonstrated that MVA-nef is a safe and immunogenic vector that could induce a strong MVA-specific T cell and antibody response both in HIV-1-infected patients and in uninfected individuals.

Keywords: smallpox vaccination; MVA; immunization