Replication-deficient mutant Herpes Simplex Virus-1 targets professional antigen presenting cells and induces efficient CD4+ T helper responses.
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.
Fiorentini
Simona
S
Department of Experimental and Applied Medicine, Section of Microbiology, University of Brescia Medical School, Piazzale Spedali Civili, 1, I-25123 Brescia, Italy.
Marconi
Peggy
P
Avolio
Manuela
M
Marini
Elena
E
Garrafa
Emirena
E
Caracciolo
Sonia
S
Rossi
Daniele
D
Bozac
Alexandra
A
Becker
Pablo D
PD
Gentili
Francesca
F
Facchetti
Fabio
F
Guzman
Carlos A
CA
Manservigi
Roberto
R
Caruso
Arnaldo
A
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000821:virology*; D015704:CD4 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000097:blood; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018259:Herpesvirus 1, Human / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D007114:Immunization; D017737:Macrophages, Peritoneal / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D011995:Recombination, Genetic; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus
D015704:CD4 Antigens; D015683:Gene Products, gag; D015483:HIV Antibodies; D015488:HIV Antigens; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1