Two previous studies were conducted on the development of a human papillomavirus infectivity and disease model using macaque females previously infected with simian immunodeficiency virus (SIV). The current study investigated 1) the utility of this model for evaluating preventative vaccine candidates for genital HPV; 2) the requirement of SIV-induced immunosuppression; and 3) the ability to produce clinically apparent HPV tissue changes (eg. condyloma) with more profound immunosuppression. Animals are being monitored for HPV reactive immune response and presence or persistence of HPV-11 nucleic acid following infectious virus challenge. Four animals are currently being studied. Two were previously infected with SIV251 and two animals are SIV naive. These animals are being followed for evidence of HPV infection, replication and generation of associated pathology. Animals are being sampled biweekly to monthly for serum, vaginal lavages and biopsy specimens. We are currently analyzing these specimens for serum anti-HPV antibodies, histochemistry and immunohistochemistry of biopsy specimens, PCR of lavage specimens, SIV serology and assessment of viral load. Serum and lavage specimens demonstrating significant immune response will be further characterized for IgG versus IgA anti-HPV response. Samples will also be analyzed using our established in vitro neutralization assay for HPV-11. Furthermore, we are in the process of establishing additional early markers of infection. HPV-11 early genes (E1^E4, E6 and E7) are being generated using the baculovirus expression system. From the recombinant proteins we plan to establish enzyme-linked immunoassays for antibody reactivity to gene products found early in the virus replication cycle. These assays, if successful, will further document that HPV-11 is replicating in the macaques. In addition antisera generated to these recombinant proteins will be tested for utility in immunohistochemistry. These would provide an additional tool for demonstration of cellular localization of HPV within the genital tract.
Showing the most recent 10 out of 408 publications
