- Poster presentation
- Open Access
Pre-clinical development of BCG.HIVA(CAT) strain, an antibiotic-free selection strain for HIV-TB pediatric vaccine
Retrovirologyvolume 9, Article number: P352 (2012)
Our starting platform was based on a heterologous BCG prime and MVA boost regimen delivering a common immunogen called HIVA. In this study, we have i) developed a BCG.HIVACAT strain containing an antibiotic free selection system (Cobra); ii) evaluated the specific HIV-1 immune responses induced after newborn BALB/c mice immunization with BCG.HIVACAT prime and MVA.HIVA.85A boost; iii) evaluated the specific-TB immune responses induced after newborn BALB/c mice immunization with BCG.HIVACAT prime and MVA.HIVA.85A boost and iv) evaluated the influence of age on specific HIV-1 immune responses using the same vaccination schedule.
7-days-old newborn and 7-weeks-old adult mice were either left unvaccinated or vaccinated subcutaneously with 105 cfu of BCG.HIVACAT or BCGwt, and 16 weeks later were boosted intramuscularly with 106 pfu MVA.HIVA.85A. The mice were sacrificed 2 weeks later. The HIV-1 and TB-specific cellular immune responses were analyzed in spleen cells by intracellular cytokine staining and IFN-γ ELISPOT.
The frequencies of TB-specific CD8 + T-cells producing IFN-γ (P11 stimulation), and spleen cells producing IFN-γ (P11, P15 and PPD stimulation), were higher in BCG.HIVACAT or BCGwt primed and MVA.HIVA.85A boosted mice compared with mice vaccinated with MVA.HIVA.85A alone (i.e. 231, 108 and 24 sfu/106 PPD stimulated splenocytes respectively). The specific HIV-1 immune responses (P18I10 stimulation) were lower in BCG.HIVACAT or BCGwt primed and MVA.HIVA.85A boosted mice compared with mice vaccinated with MVA.HIVA.85A alone (i.e. 270, 276 and 412 sfu/106 P18I10 stimulated splenocytes respectively). When adult and newborn mice were immunized using the same vaccination schedule, the HIV-1-specific immune responses in adult mice were higher than in newborn mice (0.45% vs 0.2% CD8+ T-cells producing IFN γ).
In conclusion we demonstrated the immunogenicity of BCG.HIVACAT and MVA.HIVA.85A in newborn mice but additional experiments should be performed in newborn mice testing different routes and doses that might provide different levels of immunogenicity.