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HIV-1 Tat-specific IgG antibodies in high-responders target a B-cell epitope in the cysteine-rich domain and block extracellular Tat efficiently

Kashi, V P and Jacob, R A and Paul, S and Nayak, Kaustuv and Satish, B and Swaminathan, Soumya and Satish, K S and Ranga, U (2009) HIV-1 Tat-specific IgG antibodies in high-responders target a B-cell epitope in the cysteine-rich domain and block extracellular Tat efficiently. Vaccine, 27 (48). pp. 6739-6747. ISSN 0264-410X

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Abstract

Tat, an important regulatory protein of HIV-1, has been implicated in HIV-related pathogenesis. Immune responses to Tat, although underrepresented, confer protection against disease progression, in natural infection and experimental immunization, making Tat an attractive vaccine candidate. Information on immune responses to Tat from India which has the second largest HIV incidence has been lacking. Herewe report a cross-sectional study evaluating the humoral response to Tat from a large number of samples from two southern states of India. 14% of the seropositive (63/447) and 4.6% of seronegative samples (7/150) harbored Tat-reactive antibodies.Asignificantnumberof the seropositive samples contained high levels of anti-Tat antibodies (31/447) which demonstrated class-switch to IgG1 and bound to Tat with high avidity. Cross-reactivity analysis showed that these antibodies interacted with Tat from different clades with variable degree withthe highest interaction with subtype-AE and the least with subtype-B Tat. Importantly, a B-cell epitope in the cysteine-rich domain was found to be the most immunodominant one and antibodies interacting with this epitope blocked extracellular Tat efficiently. To the best of our knowledge this is the first report on immune responses to Tat from Indian populations and the data presented here could significantly contribute to HIV Tat vaccine design.

NIRT Creators:
NIRT CreatorsEmail
Item Type: Article
Uncontrolled Keywords: HIV-1; Subtype C; Tat; Humoral immune response; Affinity maturation; Isotype switch; India; Natural antibody; IgG; Tat vaccine
Subjects: HIV
Tuberculosis > HIV - Basic Science
Divisions: Basic Science Research > Immunology
Depositing User: Dr. Rathinasabapati R
Date Deposited: 21 Nov 2017 10:36
Last Modified: 21 Nov 2017 10:36
URI: http://eprints.nirt.res.in/id/eprint/979

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