Chimeric Human Papilloma Virus–Simian/Human Immunodeficiency Virus Virus-like-Particle Vaccines: Immunogenicity and Protective Efficacy in Macaques

• Published in: Virology (New York, N.Y.) Vol. 301; no. 1; pp. 176 - 187
• Main Authors: Dale, C.Jane, Liu, Xiaosong Song, De Rose, Robert, Purcell, Damian F.J., Anderson, Jenny, Xu, Yan, Leggatt, Graham R., Frazer, Ian H., Kent, Stephen J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.09.2002
• Subjects: Animals; Antibodies, Viral - biosynthesis; Chimera; DNA vaccine; HIV; HIV-1 - immunology; human papilloma virus; Interferon-gamma - biosynthesis; Lymphocyte Activation; Macaca nemestrina; macaques; Papillomaviridae - immunology; Papillomavirus Vaccines; Reassortant Viruses - immunology; SAIDS Vaccines - immunology; T-Lymphocytes - immunology; Vaccination; vaccine; Vaccines, DNA - immunology; Vaccines, Synthetic - immunology; Virion - immunology; virus-like-particle; DNA vaccine; vaccine; human papilloma virus; HIV; macaques; virus-like-particle
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.2002.1589

Vaccines to efficiently block or limit sexual transmission of both HIV and human papilloma virus (HPV) are urgently needed. Chimeric virus-like-particle (VLP) vaccines consisting of both multimerized HPV L1 proteins and fragments of SIV gag p27, HIV-1 tat, and HIV-1 rev proteins (HPV–SHIV VLPs) were constructed and administered to macaques both systemically and mucosally. An additional group of macaques first received a priming vaccination with DNA vaccines expressing the same SIV and HIV-1 antigens prior to chimeric HPV–SHIV VLP boosting vaccinations. Although HPV L1 antibodies were induced in all immunized macaques, weak antibody or T cell responses to the chimeric SHIV antigens were detected only in animals receiving the DNA prime/HPV–SHIV VLP boost vaccine regimen. Significant but partial protection from a virulent mucosal SHIV challenge was also detected only in the prime/boosted macaques and not in animals receiving the HPV–SHIV VLP vaccines alone, with three of five prime/boosted animals retaining some CD4+ T cells following challenge. Thus, although some immunogenicity and partial protection was observed in non-human primates receiving both DNA and chimeric HPV–SHIV VLP vaccines, significant improvements in vaccine design are required before we can confidently proceed with this approach to clinical trials.