An Adenoviral-Based Mucosal Vaccine for AIDS

说明（由申请人提供）：艾滋病是一个全球性的健康问题，有3 600万人感染了艾滋病毒，估计每年有500万新感染病例。这些数字表明需要一种预防性疫苗，以防止该疾病的进一步传播。尽管在艾滋病疫苗研究方面做出了巨大努力，但传统的疫苗开发方法未能生产出有效的艾滋病毒感染疫苗。除了针对包膜的体液免疫反应外，最近的疫苗工作主要集中在引发针对艾滋病毒结构蛋白的细胞免疫反应。通过这种方法，基于腺病毒载体的疫苗已显示出作为人类艾滋病毒疫苗的巨大潜力。腺病毒载体引起强烈的先天免疫反应，这对诱导强烈的细胞免疫反应有很大的帮助。此外，腺病毒是优良的粘膜疫苗。然而，腺病毒疫苗的一个主要缺点是人类对腺病毒的预先免疫，这可能限制其效力。

DESCRIPTION (provided by applicant): AIDS is a worldwide health problem with 36 million people infected with HIV and estimated 5 million new infections occurring per year. These numbers indicate the need for a prophylactic vaccine to prevent the further spread of the disease. Despite tremendous efforts in AIDS vaccine research, traditional methods of vaccine development have failed to produce an effective vaccine for HIV infection. Recent vaccine efforts have focused on eliciting cellular immune responses directed against structural proteins of HIV instead/in addition to targeting humoral immune responses to the envelope. With that approach, adenoviral vector based vaccines have shown a great potential as vaccines for HIV in humans. Adenoviral vectors elicit strong innate immune responses, which greatly aid in inducing strong cellular immune responses. Moreover, adenoviruses are excellent as mucosal vaccines. However, one major drawback of adenoviral vaccines is prior immunity to adenoviruses in human, which could limit their efficacy. We propose to utilize a PEGylation technique to mask our Adeno-based AIDS vaccine vector, Ad/HIV, and test its efficacy in vivo. We propose to evaluate innate immune responses induced by the mucosal administration of PEGylated Ad/HIV (via intranasal route) and cellular immune responses (CTL and cytokine profiles) directed to HIV immunogen; gag encoded by the adenovector. In addition, we will determine both systemic and mucosal immune responses generated to PEGylated Ad/HIV. We will test the efficacy of PEGylated Ad/HIV both in naive mice and in mice with pre-existing immunity to adenoviruses. The results from this study will provide the groundwork for the development of a highly effective mucosal AIDS vaccine that can be repeatedly administered to patients with high efficacy.