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

Caputo, Antonella; Gavioli, Riccardo; Bellino, Stefania; Longo, Olimpia; Tripiciano, Antonella; Francavilla, Vittorio; Sgadari, Cecilia; Paniccia, Giovanni; Titti, Fausto; Cafaro, Aurelio; Ferrantelli, Flavia; Monini, Paolo; Ensoli, Fabrizio; Ensoli, Barbara

doi:10.1080/08830180903013026

Cited by 38 publications

(36 citation statements)

References 264 publications

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“…In addition to its major intracellular role as a regulator of transcription, Tat has distinct extracellular functions in viral pathogenesis and replication (45,47). Therefore, HIV-1 Tat has been targeted by candidate AIDS vaccines (41,47,48). Tat consists of 86 to 101 amino acids and can be divided into six different functional domains: (i) the NT prolinerich region (residues 1 to 21), (ii) the cysteine-rich region (residues 22 to 37), (iii) the core region (residues 38 to 48), (iv) the basic region (residues 49 to 59),(v) the glutamine-rich region (residues 60 to 72), and (vi) the C terminus (47).…”

Section: Discussionmentioning

confidence: 99%

Novel Biopanning Strategy To Identify Epitopes Associated with Vaccine Protection

Bachler

Humbert

Palikuqi

et al. 2013

J Virol

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cIdentifying immune correlates of protection is important to develop vaccines against infectious diseases. We designed a novel, universally applicable strategy to profile the antibody (Ab) repertoire of protected vaccine recipients, using recombinant phages encoding random peptide libraries. The new approach, termed "protection-linked (PL) biopanning," probes the Ab paratopes of protected vaccinees versus those with vaccine failure. As proof of concept, we screened plasma samples from vaccinated rhesus macaques (RMs) that had completely resisted multiple mucosal challenges with R5-tropic simian-human immunodeficiency viruses (SHIVs). The animals had been immunized with a multicomponent vaccine (multimeric HIV-1 gp160, HIV-1 Tat, and SIV Gag-Pol particles). After PL biopanning, we analyzed the phagotopes selected for amino acid homologies; in addition to the expected Env mimotopes, one recurring motif reflected the neutralizing Ab epitope at the N terminus (NT) of HIV-1 Tat. Subsequent binding and functional assays indicated that anti-Tat NT Abs were present only in completely or partially protected RMs; peak viremia of the latter was inversely correlated with anti-Tat NT Ab titers. In contrast, highly viremic, unvaccinated controls did not develop detectable Abs against the same epitope. Based upon the protective effect observed in vivo, we suggest that Tat should be included in multicomponent HIV-1 vaccines. Our data highlight the power of the new PL-biopanning strategy to identify Ab responses with significant association to vaccine protection, regardless of the mechanism(s) or targets of the protective Abs. PL biopanning is also unbiased with regard to pathogens or disease model, making it a universal tool.T he design of a safe, effective vaccine is desirable to control the AIDS pandemic. In order to improve future vaccine candidates, it is important to understand the protective mechanism(s) leading to reduced virus acquisition (1). Thus, correlates of infection risk for the recent RV144 vaccine efficacy trial (2) are the subject of intense study (3,4). However, additional information can be gained by dissecting immune responses in biologically relevant animal models where immunization induced complete protection from immunodeficiency virus challenge(s) (5, 6).Recent results of active (7,8) and passive (9) immunization trials in humans and in nonhuman primates suggested that antihuman immunodeficiency virus type 1 (HIV-1) Env antibodies (Abs) can have protective roles even in the absence of virus neutralization, implying that other Ab-mediated mechanisms may be involved in preventing mucosal virus acquisition. Thus, the ability to profile Ab epitopes associated with protection might help to identify potential targets for future HIV-1 vaccines.Random peptide phage display has been used to dissect Ab responses in the context of primate immunodeficiency virus infections, and several studies have identified HIV-1 or simian-human immunodeficiency virus (SHIV)-specific peptides (10-14). We developed a novel epitope...

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Section: Discussionmentioning

confidence: 99%

Novel Biopanning Strategy To Identify Epitopes Associated with Vaccine Protection

Bachler

Humbert

Palikuqi

et al. 2013

J Virol

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“…[5][6][7][8][9][10][11] Thus, the inclusion of Tat in preventive and therapeutic vaccines has been pursued by several groups showing promising results in nonhuman primates [12][13][14][15][16] and in phase I and II clinical trials. [16][17][18][19] However, the development of vaccines able to induce protective responses has to face some major challenges such as: i) the compliance requested for mass immunizations; ii) the induction of immune responses in mucosal tissues, which are the predominant sites of HIV acquisition; 20 and iii) the isotypes of antibodies elicited, which may influence the level of vaccine efficacy. 21 These factors may be modulated by the administration route.…”

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confidence: 99%

Effects of different routes of administration on the immunogenicity of the Tat protein and a Tat-derived peptide

Finessi

Nicoli

Gallerani

et al. 2015

Human Vaccines & Immunotherapeutics

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The use of the Tat protein of HIV in vaccines against AIDS showed promising results in primate and human studies. To characterize the impact of the administration route on the induction of humoral responses at systemic and mucosal levels, we compared intradermal, intramuscular and mucosal immunizations with Tat and a Tat-derived peptide. Mice were immunized with the Tat protein by different routes and the titer and isotype of anti-Tat antibodies were assessed in serum and mucosal lavages. Intramuscular and intradermal administrations showed comparable immunogenicity, while the mucosal administration was unable to induce IgM in serum and IgG at mucosal sites but showed superior immunogenicity in terms of IgA induction. Anti-Tat antibodies were also obtained upon vaccination with the immunodominant Tat 1–20 peptide which was, however, less immunogenic than the whole Tat protein

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“…Thus, the understanding of the signaling pathways implicated in the stimulation of virus replication or in the production of immunopathogenic cytokines may suggest possible targeted therapeutic approaches to neutralize such key steps. Taking into account the role of Tat protein in viral replication and induction of immunological and neurological disorders, this Tat protein represents a potential vaccine candidate (Caputo, Gavioli et al 2009). Tat protein appears to be an effective candidate to include for an HIV vaccine, since its gene product is produced early during the viral life cycle.…”

Section: Resultsmentioning

confidence: 99%

HIV Infection «HIV Tat Protein, a Key Factor in Pathogenesis and Immune System Dysregulation: Implication of IL-10»

Haij¹,

Planès²,

Mzoughi³

et al. 2011

HIV-Host Interactions

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

Cited by 38 publications

References 264 publications

Novel Biopanning Strategy To Identify Epitopes Associated with Vaccine Protection

Novel Biopanning Strategy To Identify Epitopes Associated with Vaccine Protection

Effects of different routes of administration on the immunogenicity of the Tat protein and a Tat-derived peptide

HIV Infection «HIV Tat Protein, a Key Factor in Pathogenesis and Immune System Dysregulation: Implication of IL-10»

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