MUCOSAL IMMUNIZATION AGAINST GENITAL TRANSMISSION OF SIV

重要的是艾滋病毒可以通过父母和疫苗传播 能够通过血液传播艾滋病毒是可取的，特别是在 静脉注射吸毒者。目的：本项目的目的是 使用SIV/恒河猴系统确定最佳免疫效果 激发保护性系统免疫反应的策略。结果 最初的免疫方案利用了可溶的HIV-1包膜抗原和 用于肌肉免疫。猴子们要么很虚弱，要么没有 对可溶性HIV-1抗原的抗体反应。这些动物是 然后用HIV-1假病毒粒子粘膜内免疫。要么是A 丙型佐剂(聚磷腈)或明矾用于所有 免疫接种。所有的动物都在感染后产生了抗体反应 最初的假病毒免疫，并加强6周的PI 同样的疫苗。全身和粘膜免疫反应中等。 这些动物被静脉注射了SIV/HIV嵌合体 病毒(Shiv)。所有的动物在挑战后都被感染了。 因为希沃克病毒是非致病性的，而且我们之前已经证明 感染非致病性病毒可以保护恒河猴免受 挑战致病SIV，这些动物将受到挑战 阴道感染有毒力的SIV。所有的动物都成功地抵抗了 挑战病毒。未来方向疫苗可以 预防阴道感染是非常重要的，而且将是 以确定这一发现是否与斯皮拉试图 不需要诱导抗-HIV粘膜免疫反应。关键词 HIV-1假病毒粒子，佐剂，粘膜免疫，阴道SIV挑战

Signifcance HIV can be transmitted parentally and a vaccine capable blood-borne transmission of HIV sis desirable especially for intravenous drug users. Objective The purpose of this project is to use the SIV/rhesus macaque system to define the best imunization strategy to elicit protective systemic immune responses. Results The initial immunization protocol utilized soluble HIV-1 env antigens and for intramuscular immunization. The monkeys made very weak or no antibody responses to the soluble HIV-1 antigens. The animal were then immunized intramucularly with HIV-1 pseudovirions. Either a propietary adjuvant (polyphosphazene) or Alum was used for all the immunizations. All the animals made antibody responses after the initial pseudovirion immunization and were boosted 6 weeks PI with the same vaccine. The systemic and mucosal immune responses were moderate and the animals were challenged intravenously with a SIV/HIV chimeric virus (SHIV) . All the animals became infected after the challenge. Because the SHIV is non pathogenic and because we have prviously shown that infection with a nonpathogenic can protect rhesus macaques from challenge with a pathogenic SIV, these animals will be challenged vaginally with virulent SIV. All the animals successfully resisted the challenge virus. Future Directions The finding that vaccines can protect against vaginal challenge is highly significant and will be pursued to determine if this finding idicates that specila attempts to elicit ant-HIV mucosal immune responses are not needed. KEYWORDS HIV-1 pseudovirions, adjuvant, mucosal immunity, vaginal SIV challenge