A phase I trial of preventive HIV vaccination with heterologous poxviral-vectors containing matching HIV-1 inserts in healthy HIV-uninfected subjects

作者：Keefer Michael C^*; Frey Sharon E; Elizaga Marnie; Metch Barbara; De Rosa Stephen C; Barroso Paulo F; Tomaras Georgia; Cardinali Massimo; Goepfert Paul; Kalichman Artur; Philippon Valerie; McElrath M Juliana; Jin Xia; Ferrari Guido; Defawe Olivier D; Mazzara Gail P; Montefiori David; Pensiero Michael; Panicali Dennis L; Corey Lawrence

来源：Vaccine, 2011, 29(10): 1948-1958.

DOI：10.1016/j.vaccine.2010.12.104

• Preventive HIV vaccine
• MVA and Fowlpox vectors
• Phase I clinical trial

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-naive participants. FPV-HIV alone was poorly immunogenic, while the high dose (10(9) pfu/2 ml) of MVA-HIV alone elicited maximal responses after two injections: CD4+ and CD8+ T-cell responses in 26/55 (47.3%) and 5/60(8.3%) of participants, respectively, and IFN-gamma ELISpot responses in 28/62(45.2%). The infrequent CD8+ T-cell responses following MVA-HIV priming were boosted only by the heterologous (FPV-HIV) construct in 14/27 (51.9%) of participants post 4th vaccination. Alternatively, HIV envelope-specific binding antibodies were demonstrated in approximately two-thirds of recipients of the homologous boosting regimen, but in less than 20% of subjects after the heterologous vector boost. Thus, a heterologous poxvirus vector prime-boost regimen can induce HIV-specific CD8+ T-cell and CD4+ T-cell responses, which may be an important feature of an optimal regimen for preventive HIV vaccination.

• 出版日期2011-2-24