Clerici M, Tacket C O, Via C S, Lucey D R, Muluk S C, Zajac R A, Boswell R N, Berzofsky J A, Shearer G M
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Eur J Immunol. 1991 Jun;21(6):1345-9. doi: 10.1002/eji.1830210603.
Healthy, human immunodeficiency virus seronegative (HIV-) volunteers were multiply immunized with a recombinant gp160 (rgp160) candidate acquired immunodeficiency syndrome (AIDS) vaccine. Peripheral blood lymphocytes from volunteers immunized with 40 micrograms or with 80 micrograms (two volunteers per group) of rgp160, as well as from control donors, were tested for T helper (Th) cell function either prior to immunization, 8 to 12 months after the third immunization, or 2 to 5 months after the fourth immunization. The Th cell functional tests included antigen-induced in vitro interleukin 2 (IL 2) production and proliferation in response to influenza A virus (FLU) and to four synthetic peptides of HIV gp120 and gp160, previously demonstrated to be recognized by T cells from HIV naturally infected patients. Our results demonstrate the following: (a) immunization of HIV- individuals with rgp160 results in IL 2 production and T cell proliferation in response to HIV determinants; (b) boosting with rgp160 enhances Th function; (c) HIV-specific Th function is up to 100-fold greater in the multiply immunized volunteers than that observed in asymptomatic, HIV-infected individuals; and (d) multiple immunization with rgp160 does not impair Th function to a non-HIV antigen such as influenza A virus. These results indicate that immunization of uninfected individuals with an HIV subunit vaccine results in much stronger Th cell immunity than does natural infection and suggests that vaccination against HIV may be possible.
健康的、人类免疫缺陷病毒血清阴性(HIV-)志愿者用重组gp160(rgp160)候选获得性免疫缺陷综合征(AIDS)疫苗进行多次免疫。对用40微克或80微克(每组两名志愿者)rgp160免疫的志愿者以及对照供体的外周血淋巴细胞,在免疫前、第三次免疫后8至12个月或第四次免疫后2至5个月进行T辅助(Th)细胞功能测试。Th细胞功能测试包括抗原诱导的体外白细胞介素2(IL-2)产生以及对甲型流感病毒(FLU)和HIV gp120及gp160的四种合成肽的增殖反应,这些肽先前已被证明可被HIV自然感染患者的T细胞识别。我们的结果表明:(a)用rgp160对HIV-个体进行免疫可导致针对HIV决定簇的IL-2产生和T细胞增殖;(b)用rgp160加强免疫可增强Th功能;(c)多次免疫的志愿者中HIV特异性Th功能比无症状HIV感染个体中观察到的功能高100倍;(d)用rgp160多次免疫不会损害对非HIV抗原如甲型流感病毒的Th功能。这些结果表明,用HIV亚单位疫苗对未感染个体进行免疫可产生比自然感染更强的Th细胞免疫,并提示针对HIV的疫苗接种可能是可行的。