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猕猴中通过靶向髂淋巴结免疫亚单位猴免疫缺陷病毒包膜和核心疫苗引发的保护性黏膜免疫。

Protective mucosal immunity elicited by targeted iliac lymph node immunization with a subunit SIV envelope and core vaccine in macaques.

作者信息

Lehner T, Wang Y, Cranage M, Bergmeier L A, Mitchell E, Tao L, Hall G, Dennis M, Cook N, Brookes R, Klavinskis L, Jones I, Doyle C, Ward R

机构信息

Department of Immunology, United Medical School, Guy's Hospital, London, UK.

出版信息

Nat Med. 1996 Jul;2(7):767-75. doi: 10.1038/nm0796-767.

Abstract

Prevention of sexually transmitted HIV infection was investigated in macaques by immunization with a recombinant SIV (simian immunodeficiency virus) envelope gp 120 and core p27 vaccine. In two independent series of experiments, we used the novel targeted iliac lymph node (TILN) route of immunization, aiming close to the iliac lymph nodes draining the genitorectal mucosa. Rectal challenge with the SIVmac 32H J5 molecular clone in two series induced total protection in four out of seven macaques immunized by TILN, compared with infection in 13 of 14 unimmunized macaques or immunized by other routes (P = 0.025). The remaining three macaques showed either a decrease in viral load ( > 90%) or transient viremia, indicating that all seven TILN-immunized macaques showed total or partial protection (P = 0.001). Protection was associated with significant increase in the iliac lymph nodes of IgA antibody-secreting cells to p27 (P < 0.02), CD8-suppressor factor (P < 0.01), and the chemokines RANTES and MIP-1 beta (P < 0.01).

摘要

通过用重组猴免疫缺陷病毒(SIV)包膜糖蛋白120和核心蛋白p27疫苗免疫猕猴,对性传播HIV感染的预防进行了研究。在两个独立的实验系列中,我们采用了新型的靶向髂淋巴结(TILN)免疫途径,目标是靠近引流生殖泌尿黏膜的髂淋巴结。在两个系列中,用SIVmac 32H J5分子克隆对直肠进行攻击,结果显示,通过TILN免疫的7只猕猴中有4只得到了完全保护,相比之下,14只未免疫或通过其他途径免疫的猕猴中有13只被感染(P = 0.025)。其余3只猕猴要么病毒载量下降(>90%),要么出现短暂病毒血症,这表明所有7只经TILN免疫的猕猴都表现出完全或部分保护(P = 0.001)。保护作用与髂淋巴结中针对p27的分泌IgA抗体的细胞、CD8抑制因子(P < 0.01)以及趋化因子RANTES和MIP-1β(P < 0.01)显著增加有关。

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