Burton D R
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10018-23. doi: 10.1073/pnas.94.19.10018.
Antibodies that bind well to the envelope spikes of immunodeficiency viruses such as HIV type 1 (HIV-1) and simian immunodeficiency virus (SIV) can offer protection or benefit if present at appropriate concentrations before viral exposure. The challenge in antibody-based HIV-1 vaccine design is to elicit such antibodies to the viruses involved in transmission in humans (primary viruses). At least two major obstacles exist. The first is that very little of the envelope spike surface of primary viruses appears accessible for antibody binding (low antigenicity), probably because of oligomerization of the constituent proteins and a high degree of glycosylation of one of the proteins. The second is that the mature oligomer constituting the spikes appears to stimulate only weak antibody responses (low immunogenicity). Viral variation is another possible obstacle that appears to present fewer problems than anticipated. Vaccine design should focus on presentation of an intact mature oligomer, increasing the immunogenicity of the oligomer and learning from the antibodies available that potently neutralize primary viruses.
如果在病毒暴露前以适当浓度存在，能与免疫缺陷病毒（如1型人类免疫缺陷病毒（HIV-1）和猿猴免疫缺陷病毒（SIV））包膜刺突紧密结合的抗体可提供保护或益处。基于抗体的HIV-1疫苗设计面临的挑战是引发针对人类传播所涉及病毒（原发性病毒）的此类抗体。至少存在两个主要障碍。第一个障碍是原发性病毒包膜刺突表面很少有区域可被抗体结合（抗原性低），这可能是由于组成蛋白的寡聚化以及其中一种蛋白的高度糖基化。第二个障碍是构成刺突的成熟寡聚体似乎仅刺激微弱的抗体反应（免疫原性低）。病毒变异是另一个可能的障碍，但其带来的问题似乎比预期的要少。疫苗设计应专注于完整成熟寡聚体的呈现、提高寡聚体的免疫原性以及借鉴可有效中和原发性病毒的现有抗体。
