BACKGROUND: The genetic diversity of human immunodeficiency virus type 1 (HIV-1) raises the question of whether vaccines that include a component to elicit antiviral T cell immunity based on a single viral genetic clade could provide cellular immune protection against divergent HIV-1 clades. Therefore, we quantified the cross-clade reactivity, among unvaccinated individuals, of anti-HIV-1 T cell responses to the infecting HIV-1 clade relative to other major circulating clades. METHODS: Cellular immune responses to HIV-1 clades A, B, and C were compared by standardized interferon- gamma enzyme-linked immunospot assays among 250 unvaccinated individuals, infected with diverse HIV-1 clades, from Brazil, Malawi, South Africa, Thailand, and the United States. Cross-clade reactivity was evaluated by use of the ratio of responses to heterologous versus homologous (infecting) clades of HIV-1. RESULTS: Cellular immune responses were predominantly focused on viral Gag and Nef proteins. Cross-clade reactivity of cellular immune responses to HIV-1 clade A, B, and C proteins was substantial for Nef proteins (ratio, 0.97 [95% confidence interval, 0.89-1.05]) and lower for Gag proteins (ratio, 0.67 [95% confidence interval, 0.62-0.73]). The difference in cross-clade reactivity to Nef and Gag proteins was significant (P<.0001). CONCLUSIONS: Cross-clade reactivity of cellular immune responses can be substantial but varies by viral protein.
BACKGROUND: The genetic diversity of human immunodeficiency virus type 1 (HIV-1) raises the question of whether vaccines that include a component to elicit antiviral T cell immunity based on a single viral genetic clade could provide cellular immune protection against divergent HIV-1 clades. Therefore, we quantified the cross-clade reactivity, among unvaccinated individuals, of anti-HIV-1 T cell responses to the infecting HIV-1 clade relative to other major circulating clades. METHODS: Cellular immune responses to HIV-1 clades A, B, and C were compared by standardized interferon- gamma enzyme-linked immunospot assays among 250 unvaccinated individuals, infected with diverse HIV-1 clades, from Brazil, Malawi, South Africa, Thailand, and the United States. Cross-clade reactivity was evaluated by use of the ratio of responses to heterologous versus homologous (infecting) clades of HIV-1. RESULTS: Cellular immune responses were predominantly focused on viral Gag and Nef proteins. Cross-clade reactivity of cellular immune responses to HIV-1 clade A, B, and C proteins was substantial for Nef proteins (ratio, 0.97 [95% confidence interval, 0.89-1.05]) and lower for Gag proteins (ratio, 0.67 [95% confidence interval, 0.62-0.73]). The difference in cross-clade reactivity to Nef and Gag proteins was significant (P<.0001). CONCLUSIONS: Cross-clade reactivity of cellular immune responses can be substantial but varies by viral protein.
Authors: Nina D Russell; Barney S Graham; Michael C Keefer; M Juliana McElrath; Steve G Self; Kent J Weinhold; David C Montefiori; Guido Ferrari; Helen Horton; Georgia D Tomaras; Sanjay Gurunathan; Lynn Baglyos; Sharon E Frey; Mark J Mulligan; Clayton D Harro; Susan P Buchbinder; Lindsey R Baden; William A Blattner; Beryl A Koblin; Lawrence Corey Journal: J Acquir Immune Defic Syndr Date: 2007-02-01 Impact factor: 3.731
Authors: Laura E Valentine; Shari M Piaskowski; Eva G Rakasz; Nathan L Henry; Nancy A Wilson; David I Watkins Journal: J Virol Date: 2007-10-24 Impact factor: 5.103
Authors: Nicholas J Maness; Levi J Yant; Chungwon Chung; John T Loffredo; Thomas C Friedrich; Shari M Piaskowski; Jessica Furlott; Gemma E May; Taeko Soma; Enrique J León; Nancy A Wilson; Helen Piontkivska; Austin L Hughes; John Sidney; Alessandro Sette; David I Watkins Journal: J Virol Date: 2008-04-02 Impact factor: 5.103
Authors: Lyle R McKinnon; Rupert Capina; Harold Peters; Mark Mendoza; Joshua Kimani; Charles Wachihi; Anthony Kariri; Makobu Kimani; Meika Richmond; Sandy Koesters Kiazyk; Keith R Fowke; Walter Jaoko; Ma Luo; T Blake Ball; Francis A Plummer Journal: J Virol Date: 2009-09-16 Impact factor: 5.103
Authors: Clayton Harro; Xiao Sun; Jon E Stek; Randi Y Leavitt; Devan V Mehrotra; Fubao Wang; Andrew J Bett; Danilo R Casimiro; John W Shiver; Mark J DiNubile; Erin Quirk Journal: Clin Vaccine Immunol Date: 2009-07-15
Authors: Lyle R McKinnon; Xiaojuan Mao; Joshua Kimani; Charles Wachihi; Christina Semeniuk; Mark Mendoza; Binhua Liang; Ma Luo; Keith R Fowke; Francis A Plummer; T Blake Ball Journal: PLoS One Date: 2009-09-11 Impact factor: 3.240