Antigenic competition in CD4(+) T cell responses in a randomized, multicenter, double-blind clinical HIV vaccine trial

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art_KALLAS_Antigenic_competition_in_CD4_T_cell_responses_in_2019.PDF (2.19 MB)
Citações na Scopus
17
Tipo de produção
article
Data de publicação
2019
Editora
AMER ASSOC ADVANCEMENT SCIENCE
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
GRUNENBERG, Nicole A.
YU, Chenchen
MANSO, Bryce
PANTALEO, Giuseppe
CASAPIA, Martin
BADEN, Lindsey R.
VALENCIA, Javier
SOBIESZCZYK, Magdalena
Hong Van Tieu
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
SCIENCE TRANSLATIONAL MEDICINE, v.11, n.519, article ID eaaw1673, 10p, 2019
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
T cell responses have been implicated in reduced risk of HIV acquisition in uninfected persons and control of viral replication in HIV-infected individuals. HIV Gag-specific T cells have been predominantly associated with post-infection control, whereas Env antigens are the target for protective antibodies; therefore, inclusion of both antigens is common in HIV vaccine design. However, inclusion of multiple antigens may provoke antigenic competition, reducing the potential effectiveness of the vaccine. HVTN 084 was a randomized, multicenter, double-blind phase 1 trial to investigate whether adding Env to a Gag/Pol vaccine decreases the magnitude or breadth of Gag/ Pol-specific T cell responses. Fifty volunteers each received one intramuscular injection of 1 x 10(10) particle units (PU) of rAd5 Gag/Pol and EnvA/B/C (3:1:1:1 mixture) or 5 x 10(9) PU of rAd5 Gag/Pol. CD4(+) T cell responses to Gag/ Pol measured 4 weeks after vaccination by cytokine expression were significantly higher in the group vaccinated without Env, whereas CD8(+) T cell responses did not differ significantly between the two groups. Mapping of individual epitopes revealed greater breadth of the Gag/Pol-specific T cell response in the absence of Env compared to Env coimmunization. Addition of an Env component to a Gag/Pol vaccine led to reduced Gag/Pol CD4(+) T cell response rate and magnitude as well as reduced epitope breadth, confirming the presence of antigenic competition. Therefore, T cell-based vaccine strategies should aim at choosing a minimalist set of antigens to reduce interference of individual vaccine components with the induction of the maximally achievable immune response.
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URI
https://observatorio.fm.usp.br/handle/OPI/34431
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MIP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/60
Artigos e Materiais de Revistas Científicas - ODS/03