Bicistronic DNA vaccines simultaneously encoding HIV, HSV and HPV antigens promote CD8⁺ T cell responses and protective immunity

• Published in: PloS one Vol. 8; no. 8; p. e71322
• Main Authors: Santana, Vinicius C, Diniz, Mariana O, Cariri, Francisco A M O, Ventura, Armando M, Cunha-Neto, Edécio, Almeida, Rafael R, Campos, Marco A, Lima, Graciela K, Ferreira, Luís C S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08-08-2013; Public Library of Science (PLoS)
• Subjects: AIDS Vaccines - immunology; AIDS Vaccines - therapeutic use; Alphapapillomavirus - genetics; Alphapapillomavirus - immunology; Animals; Antigens; Antigens, Viral - genetics; Antigens, Viral - immunology; Biology; Cancer; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cytotoxicity; Deoxyribonucleic acid; Disease control; DNA; DNA vaccines; Female; Gag protein; Gene expression; Genetic engineering; Herpes simplex; Herpes Simplex - immunology; Herpes Simplex - prevention & control; Herpes Simplex Virus Vaccines - immunology; Herpes Simplex Virus Vaccines - therapeutic use; Herpes viruses; HIV; HIV - genetics; HIV - immunology; HIV Infections - immunology; HIV Infections - prevention & control; Human immunodeficiency virus; Human papillomavirus; Humans; Immunity; Immunization; Immunology; Implantation; Infections; Laboratories; Latent infection; Lymphocytes; Lymphocytes T; Medicine; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Papillomavirus Infections - immunology; Papillomavirus Infections - prevention & control; Papillomavirus Vaccines - immunology; Papillomavirus Vaccines - therapeutic use; Proteins; Simplexvirus - genetics; Simplexvirus - immunology; Surgical implants; T cell receptors; Tumor cells; Tumors; Vaccines; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Vaccines, DNA - therapeutic use; Viral envelope proteins; Virology; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0071322

Millions of people worldwide are currently infected with human papillomavirus (HPV), herpes simplex virus (HSV) or human immunodeficiency virus (HIV). For this enormous contingent of people, the search for preventive and therapeutic immunological approaches represents a hope for the eradication of latent infection and/or virus-associated cancer. To date, attempts to develop vaccines against these viruses have been mainly based on a monovalent concept, in which one or more antigens of a virus are incorporated into a vaccine formulation. In the present report, we designed and tested an immunization strategy based on DNA vaccines that simultaneously encode antigens for HIV, HSV and HPV. With this purpose in mind, we tested two bicistronic DNA vaccines (pIRES I and pIRES II) that encode the HPV-16 oncoprotein E7 and the HIV protein p24 both genetically fused to the HSV-1 gD envelope protein. Mice i.m. immunized with the DNA vaccines mounted antigen-specific CD8⁺ T cell responses, including in vivo cytotoxic responses, against the three antigens. Under experimental conditions, the vaccines conferred protective immunity against challenges with a vaccinia virus expressing the HIV-derived protein Gag, an HSV-1 virus strain and implantation of tumor cells expressing the HPV-16 oncoproteins. Altogether, our results show that the concept of a trivalent HIV, HSV, and HPV vaccine capable to induce CD8⁺ T cell-dependent responses is feasible and may aid in the development of preventive and/or therapeutic approaches for the control of diseases associated with these viruses.