Crotty Shane, Andino Raul
Department of Microbiology and Immunology, University of California, 513 Parnassus Ave., Box 0414, San Francisco, CA 94143, USA.
Adv Drug Deliv Rev. 2004 Apr 19;56(6):835-52. doi: 10.1016/j.addr.2003.10.042.
Sexual transmission is the major route for the spread of the human immunodeficiency virus (HIV) in the AIDS pandemic progression. Most attempts to develop a protective HIV vaccine have failed despite eliciting strong systemic immune responses. The basic hypothesis of our poliovirus vaccine vector strategy is that essential requirements for protective immunization against HIV and other related lentiviruses may involve (1) induction of mucosal immunity and (2) immunological responses against multiple viral antigens. To test this hypothesis, we have developed replication-competent poliovirus recombinants, based on the Sabin poliovirus vaccine strain viruses, that carry and express antigens derived from the simian immunodeficiency virus (SIV). Because there are no good immunological correlates for complete protection against SIV infection, we have elected to express the entire SIV genome in defined, discrete overlapping fragments. With this approach all the potentially important antigenic sequences can be effectively expressed at local mucosal sites by the inoculation of a cocktail of recombinant polioviruses that carries a complete set of SIV antigens. Infection of susceptible mice and cynomolgus monkeys with poliovirus-SIV cocktails elicits serum and secretory humoral responses, as well as a strong cellular immunity to the inserted sequences. Most importantly, we have demonstrated that vaccination of cynomolgus monkeys with poliovirus-SIV cocktails protects against infection and AIDS after intravaginal challenge with highly pathogenic SIV(mac)251.
性传播是人类免疫缺陷病毒（HIV）在艾滋病大流行进程中传播的主要途径。尽管能引发强烈的全身免疫反应，但大多数研发保护性HIV疫苗的尝试都失败了。我们脊髓灰质炎病毒疫苗载体策略的基本假设是，针对HIV和其他相关慢病毒进行保护性免疫的基本要求可能包括：（1）诱导黏膜免疫；（2）针对多种病毒抗原的免疫反应。为了验证这一假设，我们基于Sabin脊髓灰质炎病毒疫苗株病毒开发了具有复制能力的脊髓灰质炎病毒重组体，这些重组体携带并表达源自猴免疫缺陷病毒（SIV）的抗原。由于目前尚无针对完全预防SIV感染的良好免疫相关指标，我们选择将整个SIV基因组以特定的、离散的重叠片段形式进行表达。通过这种方法，接种携带全套SIV抗原的重组脊髓灰质炎病毒混合物，所有潜在重要的抗原序列都能在局部黏膜部位有效表达。用脊髓灰质炎病毒 - SIV混合物感染易感小鼠和食蟹猴会引发血清和分泌性体液反应，以及对插入序列的强烈细胞免疫。最重要的是，我们已经证明，用脊髓灰质炎病毒 - SIV混合物对食蟹猴进行疫苗接种后，在经阴道用高致病性SIV（mac）251攻击时可预防感染和艾滋病。
