Lu Shan, Grimes Serrano Jill M, Wang Shixia
Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Curr HIV Res. 2010 Dec;8(8):622-9. doi: 10.2174/157016210794088290.
A major hurdle in the development of a global HIV-1 vaccine is viral diversity. For close to three decades, HIV vaccine development has focused on either the induction of T cell immune responses or antibody responses, and only rarely on both components. After the failure of the STEP trial, the scientific community concluded that a T cell-based vaccine would likely not be protective if the T cell immune responses were elicited against only a few dominant epitopes. Similarly, for vaccines focusing on antibody responses, one of the main criticisms after VaxGen's failed Phase III trials was on the limited antigen breadth included in the two formulations used. The successes of polyvalent vaccine approaches against other antigenically variable pathogens encourage implementation of the same approach for the design of HIV-1 vaccines. A review of the existing HIV-1 vaccination approaches based on the polyvalent principle is included here to provide a historical perspective for the current effort of developing a polyvalent HIV-1 vaccine. Results summarized in this review provide a clear indication that the polyvalent approach is a viable one for the future development of an effective HIV vaccine.
全球人类免疫缺陷病毒1型(HIV-1)疫苗研发中的一个主要障碍是病毒的多样性。近三十年来,HIV疫苗的研发主要集中在诱导T细胞免疫反应或抗体反应上,很少同时关注这两个方面。STEP试验失败后,科学界得出结论,如果T细胞免疫反应仅针对少数优势表位引发,基于T细胞的疫苗可能无法起到保护作用。同样,对于专注于抗体反应的疫苗,VaxGen公司三期试验失败后,主要批评之一是所使用的两种制剂中包含的抗原广度有限。针对其他抗原可变病原体的多价疫苗方法取得的成功,促使人们在HIV-1疫苗设计中采用同样的方法。本文对基于多价原则的现有HIV-1疫苗接种方法进行了综述,为当前研发多价HIV-1疫苗的努力提供历史视角。本综述总结的结果清楚地表明,多价方法对于未来有效HIV疫苗的开发是可行的。