黏膜艾滋病疫苗可降低猕猴黏膜感染后肠道储存库及血液中的疾病发生率和病毒载量。

Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaques.

作者信息

Belyakov I M, Hel Z, Kelsall B, Kuznetsov V A, Ahlers J D, Nacsa J, Watkins D I, Allen T M, Sette A, Altman J, Woodward R, Markham P D, Clements J D, Franchini G, Strober W, Berzofsky J A

机构信息

Molecular Immunogenetics and Vaccine Research Section, Metabolism Branch, National Cancer Institute, Bethesda, Maryland, USA.

出版信息

Nat Med. 2001 Dec;7(12):1320-6. doi: 10.1038/nm1201-1320.

DOI:10.1038/nm1201-1320

PMID:11726972

Abstract

Given the mucosal transmission of HIV-1, we compared whether a mucosal vaccine could induce mucosal cytotoxic T lymphocytes (CTLs) and protect rhesus macaques against mucosal infection with simian/human immunodeficiency virus (SHIV) more effectively than the same vaccine given subcutaneously. Here we show that mucosal CTLs specific for simian immunodeficiency virus can be induced by intrarectal immunization of macaques with a synthetic-peptide vaccine incorporating the LT(R192G) adjuvant. This response correlated with the level of T-helper response. After intrarectal challenge with pathogenic SHIV-Ku2, viral titers were eliminated more completely (to undetectable levels) both in blood and intestine, a major reservoir for virus replication, in intrarectally immunized animals than in subcutaneously immunized or control macaques. Moreover, CD4+ T cells were better preserved. Thus, induction of CTLs in the intestinal mucosa, a key site of virus replication, with a mucosal AIDS vaccine ameliorates infection by SHIV in non-human primates.

摘要

鉴于HIV-1的黏膜传播特性，我们比较了黏膜疫苗是否比皮下注射相同疫苗更有效地诱导黏膜细胞毒性T淋巴细胞（CTL），并保护恒河猴免受猿猴/人类免疫缺陷病毒（SHIV）的黏膜感染。在此我们表明，用含有LT（R192G）佐剂的合成肽疫苗经直肠免疫猕猴，可诱导出针对猿猴免疫缺陷病毒的黏膜CTL。这种反应与辅助性T细胞反应水平相关。在用致病性SHIV-Ku2经直肠攻击后，与皮下免疫或对照猕猴相比，经直肠免疫的动物血液和肠道（病毒复制的主要储存部位）中的病毒滴度被更彻底地清除（至检测不到的水平）。此外，CD4+T细胞得到了更好的保存。因此，用黏膜艾滋病疫苗在病毒复制的关键部位——肠道黏膜中诱导CTL，可改善非人灵长类动物受SHIV感染的情况。