Mucosal delivery of the human immunodeficiency virus-1 Tat protein in mice elicits systemic neutralizing antibodies, cytotoxic T lymphocytes and mucosal IgA

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

“…The antibody response was predominantly focused at the N-terminal and basic functional domains of the protein represented by peptides 1-15, 1-20 and 44-61. These results extend previous observations demonstrating the immunodominance of these epitopes after intranasal immunization [24,25] and suggest that sTat is processed and presented by epidermal Langerhans cells (LC) the same way as by the dendritic cells of the mucosal epithelium. These epitopes are generally conserved and play a critical role in the cellular uptake of Tat and transactivation [26][27][28][29].…”

“…It is composed of 86-101 amino acid residues (depending on the isolate) encoded by two exons. The first 72 amino acid residues (encoded by the first exon) are organized into three functional domains: (i) an acidic N-terminal region (aa [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] that binds to cell surface CD26 and is thought to mediate immunosuppressive activity [3]; (ii) a cysteine-rich domain (aa [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] that mediates binding to chemokine receptors [4]; and (iii) the basic domain (aa 41-60). The latter domain is responsible for the internalization of extracellular Tat and its import into the nucleus and is also required for binding to short RNA transcripts containing the viral transactivation-responsive element (TAR) [5,6].…”

HIV-1 Tat-Based Vaccines: An Overview and Perspectives in the Field of HIV/AIDS Vaccine Development

“…This evidence thereby suggests that the presence of anti-Tat antibodies may predict the clinical outcome and that the induction of humoral responses against Tat, either during the course of the natural infection or by vaccination, may contrast the progression to the disease. The predominant antibody responses to Tat have been mapped at amino acids 1-20 and 36-50, which are highly conserved among different HIV subtypes [120] and are key for Tat function and contain B [133,144] and T cell [115,[145][146][147][148][149][150][151] epitopes. However, antibody responses against other functional domains of Tat are also detected during infection, including the cysteine, basic, and carboxy-terminal regions [120-122, 126, 129, 152, 153].…”

Protection of Mice from Rabies by Intranasal Immunization with Inactivated Rabies Virus

“…it is easier to vaccinate animals with the mucosal method than the parenteral method, and unlike parenteral vaccines, mucosal vaccination stimulates sigA production in mucosal tissues, which could effectively inhibit the entry of pathogens that invade their hosts via the mucosal route. The efficacy of mucosal immunization has been well documented for mucosal pathogens, such as influenza virus, Newcastle disease virus, foot and mouth disease virus, Aujeszky's disease virus, hiV and Ascaris suum [15,19,22,25,26,28,29,30]. Furthermore, mucosal immunization can also stimulate systemic immune responses, such as serum igG production and cytokine production by T cells [28,29].…”

“…recently, mucosal immunization using recombinant proteins or inactivated pathogens has been studied for both mucosal [15,19,22,25,26,28,29,30] and nonmucosal pathogens [1,2,16,23]. Due to the ease of administration and the efficacy against both mucosal and non-mucosal pathogens, a mucosal immunization strategy with recombinant protein is considered as one of the most promising alternative vaccination methods.…”