Replication-deficient mutant Herpes Simplex Virus-1 targets professional antigen presenting cells and induces efficient CD4 + T helper responses

• Published in: Microbes and infection 2007-07, Vol.9 (8), p.988-996
• Main Authors: Fiorentini, Simona, Marconi, Peggy, Avolio, Manuela, Marini, Elena, Garrafa, Emirena, Caracciolo, Sonia, Rossi, Daniele, Bozac, Alexandra, Becker, Pablo D., Gentili, Francesca, Facchetti, Fabio, Guzman, Carlos A., Manservigi, Roberto, Caruso, Arnaldo
• Format: Article
• Language: English
• Subjects: Animals; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - virology; Biological and medical sciences; CD4 Antigens; CD4-Positive T-Lymphocytes - immunology; Female; Fundamental and applied biological sciences. Psychology; gag Gene Products, Human Immunodeficiency Virus; Gene Products, gag - genetics; Gene Products, gag - immunology; Gene Products, gag - metabolism; Genetic Vectors; Helper T-cells; Herpes simplex virus; Herpesvirus 1, Human - genetics; Herpesvirus 1, Human - immunology; Herpesvirus 1, Human - pathogenicity; HIV Antibodies - blood; HIV Antigens - genetics; HIV Antigens - immunology; HIV Antigens - metabolism; HIV-1; HSV-1; Human immunodeficiency virus; Humans; Immunization; Macrophages, Peritoneal - virology; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Mutation; Recombination, Genetic; T-Lymphocytes, Helper-Inducer - immunology; Viral Proteins - genetics; Viral Proteins - immunology; Viral Proteins - metabolism; Virology; Virus Replication
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2007.04.001

Both neutralizing antibodies and cytotoxic T-cells are necessary to control a viral infection. However, vigorous T helper responses are essential for their elicitation and maintenance. Here we show that a recombinant replication-deficient Herpes Simplex Virus (HSV)-1 vector encoding the Human Immunodeficiency Virus (HIV)-1 matrix protein p17 (T0-p17) was capable of infecting professional antigen presenting cells (APCs) in vitro and in vivo. The injection of T0-p17 in the mouse dermis generated a strong p17-specific CD4 + T helper response preceding both p17-specific humoral and effector T cell responses. Moreover, we show that T0-p17 infection did not interfere with the endogenous processing of the transgene encoded antigen, since infected APCs were able to evoke a strong recall response in vitro. Our results demonstrate that replication-deficient HSV vectors can be appealing candidates for the development of vaccines able to trigger T helper responses.