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Title: The Grafting of Universal T-Helper Epitopes Enhances Immunogenicity of HIV-1 Tat Concurrently Improving Its Safety Profile
Authors: Kashi, Venkatesh P.
Jacob, Rajesh A.
Shamanna, Raghavendra A.
Menon, Malini
Balasiddaiah, Anangi
Varghese, Rebu K.
Bachu, Mahesh
Ranga, Udaykumar
Keywords: Human-Immunodeficiency-Virus
Clade-Specific Differences
Type-1 Tat
Neutralizing Antibodies
Cynomolgus Monkeys
Rhesus Macaques
89.6P Challenge
Issue Date: 2014
Publisher: Public Library of Science
Citation: Kashi, VP; Jacob, RA; Shamanna, RA; Menon, M; Balasiddaiah, A; Varghese, RK; Bachu, M; Ranga, U, The Grafting of Universal T-Helper Epitopes Enhances Immunogenicity of HIV-1 Tat Concurrently Improving Its Safety Profile. PLoS One 2014, 9 (12) , e114155
PLoS One
Abstract: Extracellular Tat (eTat) plays an important role in HIV-1 pathogenesis. The presence of anti-Tat antibodies is negatively correlated with disease progression, hence making Tat a potential vaccine candidate. The cytotoxicity and moderate immunogenicity of Tat however remain impediments for developing Tat-based vaccines. Here, we report a novel strategy to concurrently enhance the immunogenicity and safety profile of Tat. The grafting of universal helper T-lymphocyte (HTL) epitopes, Pan DR Epitope (PADRE) and Pol(711) into the cysteine rich domain (CRD) and the basic domain (BD) abolished the transactivation potential of the Tat protein. The HTL-Tat proteins elicited a significantly higher titer of antibodies as compared to the wild-type Tat in BALB/c mice. While the N-terminal epitope remained immunodominant in HTL-Tat immunizations, an additional epitope in exon-2 was recognized with comparable magnitude suggesting a broader immune recognition. Additionally, the HTL-Tat proteins induced cross-reactive antibodies of high avidity that efficiently neutralized exogenous Tat, thus blocking the activation of a Tat-defective provirus. With advantages such as presentation of multiple B-cell epitopes, enhanced antibody response and importantly, transactivation-deficient Tat protein, this approach has potential application for the generation of Tat-based HIV/AIDS vaccines.
Description: Open Access
ISSN: 1932-6203
Appears in Collections:Research Papers (Ravi Manjithaya)

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