Comparison of DNA vaccines producing HIV-1 Gag and LAMP/Gag chimera in rhesus macaques reveals antigen-specific T-cell responses with distinct phenotypes

Antonio Valentin; Priya Chikhlikar; Vainav Patel; Margherita Rosati; Milton Maciel; Kern Hee Chang; Peter Silvera; Barbara K. Felber; George N. Pavlakis; J. Thomas August; Ernesto T.A. Marques

doi:10.1016/j.vaccine.2009.05.093

Comparison of DNA vaccines producing HIV-1 Gag and LAMP/Gag chimera in rhesus macaques reveals antigen-specific T-cell responses with distinct phenotypes

Antonio Valentin, Priya Chikhlikar, Vainav Patel, Margherita Rosati, Milton Maciel, Kern Hee Chang, Peter Silvera, Barbara K. Felber, George N. Pavlakis, J. Thomas August, Ernesto T.A. Marques

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

Abstract

Optimized DNA expression vectors encoding the native HIV-1 Gag or a fusion of Gag with the lysosomal membrane associated protein 1 (LAMP) were compared for immunogenicity upon intramuscular DNA delivery in rhesus macaques. Both vaccines elicited CD4⁺ T-cell responses, but with significant differences in the phenotype of the Gag-specific cells: the native Gag induced CD4⁺ responses with a phenotype of central memory-like T cells (CD28⁺ CD45RA^-), whereas the LAMP/Gag chimera induced CD4⁺ responses with effector memory phenotype (CD28^- CD45RA^-). Antigen-specific T cells producing both IFN-γ and TNFα were found in the animals receiving the native Gag, whereas the LAMP/Gag chimera induced humoral responses faster. These results demonstrate that modification of intracellular Gag trafficking results in the induction of distinct immune responses. Combinations of DNA vectors encoding both forms of antigen may be more potent in eliciting anti-HIV-1 immunity.

Original language	English (US)
Pages (from-to)	4840-4849
Number of pages	10
Journal	Vaccine
Volume	27
Issue number	35
DOIs	https://doi.org/10.1016/j.vaccine.2009.05.093
State	Published - Jul 30 2009
Externally published	Yes

Keywords

CD4
CD8
Central memory
Effector memory
IFN-gamma
IL-2
T cells
TNF-alpha

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2009.05.093

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Valentin, A., Chikhlikar, P., Patel, V., Rosati, M., Maciel, M., Chang, K. H., Silvera, P., Felber, B. K., Pavlakis, G. N., August, J. T., & Marques, E. T. A. (2009). Comparison of DNA vaccines producing HIV-1 Gag and LAMP/Gag chimera in rhesus macaques reveals antigen-specific T-cell responses with distinct phenotypes. Vaccine, 27(35), 4840-4849. https://doi.org/10.1016/j.vaccine.2009.05.093

Valentin, A, Chikhlikar, P, Patel, V, Rosati, M, Maciel, M, Chang, KH, Silvera, P, Felber, BK, Pavlakis, GN, August, JT & Marques, ETA 2009, 'Comparison of DNA vaccines producing HIV-1 Gag and LAMP/Gag chimera in rhesus macaques reveals antigen-specific T-cell responses with distinct phenotypes', Vaccine, vol. 27, no. 35, pp. 4840-4849. https://doi.org/10.1016/j.vaccine.2009.05.093

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title = "Comparison of DNA vaccines producing HIV-1 Gag and LAMP/Gag chimera in rhesus macaques reveals antigen-specific T-cell responses with distinct phenotypes",

abstract = "Optimized DNA expression vectors encoding the native HIV-1 Gag or a fusion of Gag with the lysosomal membrane associated protein 1 (LAMP) were compared for immunogenicity upon intramuscular DNA delivery in rhesus macaques. Both vaccines elicited CD4+ T-cell responses, but with significant differences in the phenotype of the Gag-specific cells: the native Gag induced CD4+ responses with a phenotype of central memory-like T cells (CD28+ CD45RA-), whereas the LAMP/Gag chimera induced CD4+ responses with effector memory phenotype (CD28- CD45RA-). Antigen-specific T cells producing both IFN-γ and TNFα were found in the animals receiving the native Gag, whereas the LAMP/Gag chimera induced humoral responses faster. These results demonstrate that modification of intracellular Gag trafficking results in the induction of distinct immune responses. Combinations of DNA vectors encoding both forms of antigen may be more potent in eliciting anti-HIV-1 immunity.",

keywords = "CD4, CD8, Central memory, Effector memory, IFN-gamma, IL-2, T cells, TNF-alpha",

author = "Antonio Valentin and Priya Chikhlikar and Vainav Patel and Margherita Rosati and Milton Maciel and Chang, {Kern Hee} and Peter Silvera and Felber, {Barbara K.} and Pavlakis, {George N.} and August, {J. Thomas} and Marques, {Ernesto T.A.}",

note = "Funding Information: We thank C. Bergamaschi and V. Kulkarni for discussions, K. Nagashima for electron microscopy, J. Bear and P. Roth for technical assistance, and T. Jones for editorial assistance. We thank Jon Warren, VRP, DAIDS for materials and support. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. ",

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AU - Valentin, Antonio

AU - Chikhlikar, Priya

AU - Patel, Vainav

AU - Rosati, Margherita

AU - Maciel, Milton

AU - Chang, Kern Hee

AU - Silvera, Peter

AU - Felber, Barbara K.

AU - Pavlakis, George N.

AU - August, J. Thomas

AU - Marques, Ernesto T.A.

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PY - 2009/7/30

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N2 - Optimized DNA expression vectors encoding the native HIV-1 Gag or a fusion of Gag with the lysosomal membrane associated protein 1 (LAMP) were compared for immunogenicity upon intramuscular DNA delivery in rhesus macaques. Both vaccines elicited CD4+ T-cell responses, but with significant differences in the phenotype of the Gag-specific cells: the native Gag induced CD4+ responses with a phenotype of central memory-like T cells (CD28+ CD45RA-), whereas the LAMP/Gag chimera induced CD4+ responses with effector memory phenotype (CD28- CD45RA-). Antigen-specific T cells producing both IFN-γ and TNFα were found in the animals receiving the native Gag, whereas the LAMP/Gag chimera induced humoral responses faster. These results demonstrate that modification of intracellular Gag trafficking results in the induction of distinct immune responses. Combinations of DNA vectors encoding both forms of antigen may be more potent in eliciting anti-HIV-1 immunity.

AB - Optimized DNA expression vectors encoding the native HIV-1 Gag or a fusion of Gag with the lysosomal membrane associated protein 1 (LAMP) were compared for immunogenicity upon intramuscular DNA delivery in rhesus macaques. Both vaccines elicited CD4+ T-cell responses, but with significant differences in the phenotype of the Gag-specific cells: the native Gag induced CD4+ responses with a phenotype of central memory-like T cells (CD28+ CD45RA-), whereas the LAMP/Gag chimera induced CD4+ responses with effector memory phenotype (CD28- CD45RA-). Antigen-specific T cells producing both IFN-γ and TNFα were found in the animals receiving the native Gag, whereas the LAMP/Gag chimera induced humoral responses faster. These results demonstrate that modification of intracellular Gag trafficking results in the induction of distinct immune responses. Combinations of DNA vectors encoding both forms of antigen may be more potent in eliciting anti-HIV-1 immunity.

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Comparison of DNA vaccines producing HIV-1 Gag and LAMP/Gag chimera in rhesus macaques reveals antigen-specific T-cell responses with distinct phenotypes

Abstract

Keywords

ASJC Scopus subject areas

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