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We evaluated replication-defective poxvirus vectors (modified vaccinia Ankara [MVA] and fowlpox [FPV]) in a homologous and heterologous vector prime-boost vaccination regimen containing matching HIV inserts (MVA-HIV and FPV-HIV) given at months 0, 1, 3, 5 and 7 in 150 healthy HIV-negative vaccinia-naïve participants. FPV-HIV alone was poorly immunogenic, while the high dose (10 9 NIH Public Access Author ManuscriptVaccine. Author manuscript; available in PMC 2011 February 24.Published in final edited form as: Vaccine. 2011 February 24; 29(10): 1948-1958. doi:10.1016/j.vaccine.2010. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript boost. Thus, a heterologous poxvirus vector prime-boost regimen can induce an HIV-specific CD8+ T-cell and CD4+ T-cell responses, which may be an important feature of an optimal regimen for preventive HIV vaccination.