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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Increased detection of HIV-specific T cell responses by combination of central sequences with comparable immunogenicity
AIDS, Volume 22, No. 4, Year 2008
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Description
OBJECTIVE: To evaluate the recognition of computationally designed, centralized HIV-1 antigens derived from clade B, C and group M sequences by individuals infected with HIV-1-M clades B and C. METHODS: Three centralized sequences have been described - consensus, ancestor and center-of-tree - each of which attempts to minimize the genetic distance to circulating viruses. It is unclear whether any of these sequences affords an advantage for T cell recognition. The ability of centralized clade B and C and group M peptides to be targeted in ELISpot assays was assessed using samples from the United States, Peru, Barbados and South Africa. RESULTS: Each of the clade-specific centralized peptide sets was equally powerful in detecting cytotoxic T cell (CTL) responses. Importantly, combination of these sets detected significantly broader responses. Although broad responses were observed in populations from which few sequences informed the design of these centralized sequences, the genetic distance between local sequences and the respective test set was inversely associated with response rates. Furthermore, the CTL reactivity in clade C-infected subjects using clade B peptides was reduced relative to within-clade peptide responses, while responses to group M peptides were comparable to within-clade peptide responses in these individuals. CONCLUSIONS: All tested centralized antigens provided a similarly potent set of antigenic peptides. However, the significantly broader responses detected using the combination of sets highlight the importance of maximizing coverage of HIV-1 sequence diversity in vaccine preparations, as well as in the evaluation of CTL responses in HIV-1-infected individuals and those vaccinated. © 2008 Lippincott Williams & Wilkins, Inc.
Authors & Co-Authors
Frahm, Nicole
United States, Boston
Massachusetts General Hospital
Nickle, David C.
United States, Seattle
University of Washington School of Medicine
Linde, Caitlyn H.
United States, Boston
Massachusetts General Hospital
Cohen, Daniel E.
United States, Boston
Fenway Community Health Center
Zuniga, Rosario
Peru, Lima
Asociación Civil Impacta Salud y Educación
Lucchetti, Aldo
Peru, Lima
Asociación Civil Impacta Salud y Educación
Roach, Timothy C.
Barbados, Bridgetown
Queen Elizabeth Hospital Bridgetown
Walker, Bruce D.
United States, Boston
Massachusetts General Hospital
United States, Chevy Chase
Howard Hughes Medical Institute
South Africa, Durban
University of Kwazulu-natal
Allen, Todd M.
United States, Boston
Massachusetts General Hospital
Korber, Bette T.
United States, Los Alamos
Los Alamos National Laboratory
United States, Santa fe
Santa fe Institute
Mullins, James I.
United States, Seattle
University of Washington School of Medicine
Brander, Christian
United States, Boston
Massachusetts General Hospital
Statistics
Citations: 38
Authors: 12
Affiliations: 9
Identifiers
Doi:
10.1097/QAD.0b013e3282f42412
Research Areas
Genetics And Genomics
Health System And Policy
Infectious Diseases
Study Locations
South Africa