Redfield R R, Birx D L, Ketter N, Tramont E, Polonis V, Davis C, Brundage J F, Smith G, Johnson S, Fowler A
Department of Retroviral Research, Walter Reed Army Institute of Research, Rockville, Md. 20850.
N Engl J Med. 1991 Jun 13;324(24):1677-84. doi: 10.1056/NEJM199106133242401.
Despite multiple antiviral humoral and cellular immune responses, infection with the human immunodeficiency virus (HIV) results in a progressively debilitating disease. We hypothesized that a more effective immune response could be generated by post-infection vaccination with HIV-specific antigens.
We performed a phase I trial of the safety and immunogenicity of a vaccine prepared from molecularly cloned envelope protein, gp160, in 30 volunteer subjects with HIV infection in Walter Reed stage 1 or 2. The vaccine was administered either on days 0, 30, and 120 or on days 0, 30, 60, 120, 150, and 180. HIV-specific humoral and cellular immune responses were measured; local and systemic reactions to vaccination, including general measures of immune function, were monitored.
In 19 of the 30 subjects both humoral and cellular immunity to HIV envelope proteins increased in response to vaccination with gp160. Seroconversion to selected envelope epitopes was observed, as were new T-cell proliferative responses to gp160. Response was associated with the CD4 cell count determined before vaccination (13 of 16 subjects [81 percent] with greater than 600 cells per milliliter responded, as compared with 6 of 14 [43 percent] with less than or equal to 600 cells per milliliter; P = 0.07) and with the number of injections administered (87 percent of subjects randomly assigned to receive six injections responded, as compared with 40 percent of those assigned to three injections; P = 0.02). Local reactions at the site of injection were mild. There were no adverse systemic reactions, including diminution of general in vitro or in vivo cellular immune function. After 10 months of follow-up, the mean CD4 count had not decreased in the 19 subjects who responded, but it had decreased by 7.3 percent in the 11 who did not respond.
This gp160 vaccine is safe and immunogenic in volunteer patients with early HIV infection. Although it is too early to know whether this approach will be clinically useful, further scientific and therapeutic evaluation of HIV-specific vaccine therapy is warranted. Similar vaccines may prove to be effective for other chronic infections.
尽管存在多种抗病毒体液免疫和细胞免疫反应，但人类免疫缺陷病毒（HIV）感染仍会导致疾病逐渐恶化。我们推测，感染后接种HIV特异性抗原可能会产生更有效的免疫反应。
我们对30名处于沃尔特·里德1期或2期的HIV感染志愿者进行了一项I期试验，以研究由分子克隆包膜蛋白gp160制备的疫苗的安全性和免疫原性。疫苗分别在第0、30和120天或第0、30、60、120、150和180天接种。检测HIV特异性体液免疫和细胞免疫反应；监测疫苗接种的局部和全身反应，包括免疫功能的一般指标。
30名受试者中有19名在接种gp160后对HIV包膜蛋白的体液免疫和细胞免疫均增强。观察到针对选定包膜表位的血清转化，以及对gp160新的T细胞增殖反应。反应与接种前测定的CD4细胞计数有关（每毫升大于600个细胞的16名受试者中有13名[81%]有反应，而每毫升小于或等于600个细胞的14名受试者中有6名[43%]有反应；P = 0.07），也与接种次数有关（随机分配接受6次注射的受试者中有87%有反应，而分配接受3次注射的受试者中有40%有反应；P = 0.02）。注射部位的局部反应较轻。没有出现不良全身反应，包括体外或体内一般细胞免疫功能的降低。经过10个月的随访，19名有反应的受试者的平均CD4计数没有下降，但11名无反应受试者的平均CD4计数下降了7.3%。
这种gp160疫苗在早期HIV感染的志愿者患者中是安全且具有免疫原性的。虽然现在判断这种方法是否具有临床实用性还为时过早，但有必要对HIV特异性疫苗疗法进行进一步的科学和治疗评估。类似的疫苗可能对其他慢性感染也有效。
