IMMUNOCONJUGATES THAT WILL BE EFFECTIVE IN ELICITING ANTI-HIV RESPONSE

感染HIV-1的早期表现是辅助性T细胞的丢失 (CD4+）细胞功能。 随后，这些细胞也被耗尽， 由于HIV-1的细胞病变效应， 由于CD 4 + T细胞是 蛋白质抗原的抗体反应所需的，缺乏 这些细胞的功能或数量将导致 对HIV-1的抗体反应减弱。 我们的开发方法 一种增强HIV-1感染者免疫反应的疫苗， 一直使用T细胞非依赖性（TI）抗原，从而绕过 需要CD 4 + T细胞。 已知流产布鲁氏菌（Brucella abortus，BA） 可以用作半抗原的载体，以刺激抗体应答， 缺乏T细胞。 之前我们发现HIV-1与 牛种布氏杆菌（BA）在小鼠体内也能引起抗HIV抗体反应 耗尽的奇数CD 4 + T细胞。 由于脂多糖（LPS）从其他 革兰氏阴性杆菌能刺激B细胞，我们决定纯化LPS 从BA，以取代BA作为载体。 这将完善使用 作为载体的BA的分子的定义的结构和消除其他 可能有毒的BA元素。 纯化来自BA的LPS并测试其生物活性。 功能活动。 将半抗原三硝基苯基（TNP）缀合至 这个LPS。 TNP-LPS（BA）表现为T非依赖性1型携带者， 抗TNP应答在（i）对TNP不应答的裸鼠中引发， T依赖性抗原和（ii）CBA/n小鼠，不响应T- 独立的2型抗原（多糖）。 TNP缀合形式的 LPS来自E.大肠杆菌和B.在C3 H/HEJ小鼠中比较流产， 巨噬细胞对脂多糖的反应不足 TNP-LPS（BA）诱导的抗- TNP属于所有四种IgG同种型。 这表明来自BA， 与EC的LPS不同，它可以刺激T细胞释放WITCH因子， 而不需要从巨噬细胞释放IL-1。

An early manifestation of infection with HIV-1 is the loss of helper T (CD4+) cell function. Subsequently these cells are also depleted in number due to cytopathic effects of HIV-1. Since CD4+ T cells are required in antibody responses to protein antigens, deficiency in function or number of these cells would be expected to result in impaired antibody responses against HIV-1. Our approach for developing a vaccine to boost immune responses in HIV-1 infected individuals has been to use T-cell independent (TI) antigens and thus bypass the requirement for CD4+ T cells. It is known that Brucella abortus (BA) can be used as a carrier for haptens to stimulate antibody responses in the absence of T cells. Previously we showed that HIV-1 conjugated to Brucella abortus (BA) elicited anti-HIV antibody responses even in mice depleted odd CD4+ T cells. Since lipopolysaccharide (LPS) from other gram negative bacilli can stimulate B cells, we decided to purify LPS from BA in order to replace BA as the carrier. This will refine the use of BA as a carrier to molecule of defined structure and eliminate other BA elements that may be toxic. LPS from BA was purified and tested for functional activity. The hapten, trinitrophenyl (TNP) was conjugated to this LPS. TNP-LPS(BA) behaved as a T-independent type 1 carrier since anti-TNP responses were elicited in (i) nude mice that do not respond to T-dependent antigens and in (ii) CBA/n mice that do not respond to T- independent type 2 antigens (polysaccharides). TNP-conjugated forms of LPS from E. Coli and B. abortus were compared in C3H/HEJ mice, which have deficient macrophage responses to LPS. TNP-LPS (BA) induced anti- TNP belonging to all four IgG isotypes. This suggests that LPS from BA, unlike LPS from EC, can stimulate release of witch factors from T cells without requiring release of IL-1 from macrophages.