A synthetic HIV‐1 Tat protein breaches the skin barrier and elicits Tat‐neutralizing antibodies and cellular immunity

The HIV‐1 Tat protein plays a critical role in the pathogenesis of HIV and has been considered as a candidate vaccine antigen. In an effort to design a non‐invasive vaccination strategy against HIV‐1 that stimulates the induction of systemic and mucosal immune responses, we studied the transcutaneous delivery of a synthetic Tat protein using cholera toxin as an adjuvant. Following immunization of BALB/c mice with various doses of Tat, IgG and IgA antibody responses were measured in the serum and vaginal washes, respectively. Serum antibodies predominantly recognized the N‐terminal and basic functional domains of the protein and exhibited neutralizing capacity against Tat‐driven transactivation. Transcutaneous immunization also elicited potent cellular immune responses against Tat and the secretion of high levels of IL‐2, IFN‐γ and IL‐6. These findings demonstrate for the first time that by using a simple and safe immunization procedure, a synthetic Tat protein can elicit potentially protective immune responses. Transcutaneous immunization may be advantageous for the non‐invasive delivery of other HIV candidate vaccine antigens.