Rubinstein A, Goldstein H, Pettoello-Mantovani M, Mizrachi Y, Bloom B R, Furer E, Althaus B, Que J U, Hasler T, Cryz S J
Albert Einstein College of Medicine, Bronx, New York 10461, USA.
AIDS. 1995 Mar;9(3):243-51.
To develop a peptide-based model for a preventive vaccine for HIV-1 infection.
Phase I trial in HIV-1-seronegative volunteers.
Adult healthy subjects HIV-1-antibody-seronegative in an enzyme-linked immunosorbent assay, screened for tuberculin [purified protein derivative (PPD)] reactivity with 2 tuberculin units PPD-administered intradermally.
Submicrogram doses of a PPD conjugate with a peptide of the primary neutralizing domain (PND) of HIV-1MN (PPD-MN-PND) were administered intradermally to tuberculin skin-test-positive and -negative volunteers.
Antibodies to the MN-PND were measured after two immunizations in 10 out of 11 PPD skin-test-positive volunteers. After the fourth immunization high-affinity antibodies were detected, which persisted for over 1 year. High titers of MN-PND-specific immunoglobulin (Ig) G and IgA were detected in the serum and saliva of all volunteers tested. Serum antibodies were cross-reactive with PND peptide from some other HIV-1 strains but neutralized only the HIV-1MN prototype. Human leukocyte antigen (HLA)-B7-restricted MN-PND-specific cytotoxic T lymphocytes (CTL) were also detected.
The PPD-MN-PND vaccine at submicrogram doses is safe and immunogenic in PPD skin-test-positive healthy adult volunteers. Long lasting humoral immune responses in the serum and saliva were possibly accompanied by HLA-B7-restricted CTL responses. This is a vaccine prototype that can be rapidly and inexpensively modified to include other peptide epitopes. It is especially suitable for use in a worldwide multibillion Bacillus Calmette-Guérin (BCG)-primed or tuberculosis-exposed population at risk for HIV-1 infection.
开发一种基于肽的预防HIV-1感染的疫苗模型。
在HIV-1血清阴性志愿者中进行的I期试验。
在酶联免疫吸附试验中HIV-1抗体血清阴性的成年健康受试者，通过皮内注射2个结核菌素单位的结核菌素[纯化蛋白衍生物（PPD）]筛查结核菌素反应性。
将亚微克剂量的与HIV-1MN主要中和结构域（PND）肽结合的PPD（PPD-MN-PND）皮内注射给结核菌素皮肤试验阳性和阴性的志愿者。
11名PPD皮肤试验阳性志愿者中有10名在两次免疫后检测到针对MN-PND的抗体。第四次免疫后检测到高亲和力抗体，其持续超过1年。在所有检测的志愿者的血清和唾液中检测到高滴度的MN-PND特异性免疫球蛋白（Ig）G和IgA。血清抗体与其他一些HIV-1毒株的PND肽发生交叉反应，但仅中和HIV-1MN原型。还检测到人类白细胞抗原（HLA）-B7限制性MN-PND特异性细胞毒性T淋巴细胞（CTL）。
亚微克剂量的PPD-MN-PND疫苗在PPD皮肤试验阳性的健康成年志愿者中是安全且具有免疫原性的。血清和唾液中持久的体液免疫反应可能伴随着HLA-B7限制性CTL反应。这是一种疫苗原型，可以快速且低成本地进行改造以纳入其他肽表位。它特别适用于全球数十亿接种卡介苗（BCG）或接触过结核病且有HIV-1感染风险人群。
