Brown Scott A, Surman Sherri L, Sealy Robert, Jones Bart G, Slobod Karen S, Branum Kristen, Lockey Timothy D, Howlett Nanna, Freiden Pamela, Flynn Patricia, Hurwitz Julia L
Department of Immunology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN, USA;
Viruses. 2010 Feb 1;2(2):435-467. doi: 10.3390/v2020435.
Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of `original antigenic sin' is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus) and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans.
目前，有超过3000万人感染了HIV-1，且每天还有数千人被感染。疫苗接种是预防病毒性疾病的最有效机制，经过25年多的研究，一种疫苗在一项晚期临床疗效试验中显示出了些许令人鼓舞的结果。对试验结果进行的改良意向性分析表明，与安慰剂组相比，疫苗组的感染率降低了约30%。该疫苗采用异源初免-加强免疫方案进行接种，在此过程中，目标抗原和递送载体均发生了改变。在此，我们研究了异源初免-加强免疫接种的复杂性。我们表明，在初免和加强接种中使用不同的递送载体有助于避免载体特异性免疫反应所造成的抑制作用。我们还表明，在加强接种中引入新抗原可能具有优势，这表明“原始抗原罪”的影响并非绝对。本文对临床前和临床研究进行了综述，包括我们自己使用重组DNA、病毒（仙台病毒或痘苗病毒）和蛋白质的三载体疫苗接种方案所开展的工作。有前景的初步结果表明，异源初免-加强策略可能为未来预防人类HIV-1感染奠定基础。
