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A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART.

Gómez CE, Perdiguero B, García-Arriaza J, Cepeda V, Sánchez-Sorzano CÓ, Mothe B, Jiménez JL, Muñoz-Fernández MÁ, Gatell JM, López Bernaldo de Quirós JC, Brander C, García F, Esteban M - PLoS ONE (2015)

Bottom Line: MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1-specific CD8 T cell responses.In addition, vaccination also triggered preferential CD8+ T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses.MVA-B vaccination represents a feasible strategy to improve T cell responses in individuals with pre-existing HIV-1-specific immunity.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.

ABSTRACT

Trial design: Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm3 and undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens) or placebo, followed by interruption of HAART.

Methods: The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination.

Results: MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1-specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8+ T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses.

Conclusion: MVA-B vaccination represents a feasible strategy to improve T cell responses in individuals with pre-existing HIV-1-specific immunity.

Trial registration: ClinicalTrials.gov NCT01571466.

No MeSH data available.


Related in: MedlinePlus

Phenotype of the HIV-1-specific CD4 and CD8 T cell responses.Frequencies of HIV-1-specific CD4 (A) and CD8 T cells (B) (directed against Env+Gag+GPN) with phenotype T central memory (TCM: CD45RA- CCR7+), T effector memory (TEM: CD45RA- CCR7-) or terminally differentiated T effector memory (TEMRA: CD45RA+ CCR7-), in vaccinees and placebos before vaccination (W0), after two (W6) or three (W18) MVA-B or placebo doses or at time of HAART interruption (W24). The boxes correspond to the individual data points and IQR at the different time points. p-values for significant differences were determined using the Wilcoxon rank sum test with continuity correction and are represented. All data are background-subtracted.
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pone.0141456.g007: Phenotype of the HIV-1-specific CD4 and CD8 T cell responses.Frequencies of HIV-1-specific CD4 (A) and CD8 T cells (B) (directed against Env+Gag+GPN) with phenotype T central memory (TCM: CD45RA- CCR7+), T effector memory (TEM: CD45RA- CCR7-) or terminally differentiated T effector memory (TEMRA: CD45RA+ CCR7-), in vaccinees and placebos before vaccination (W0), after two (W6) or three (W18) MVA-B or placebo doses or at time of HAART interruption (W24). The boxes correspond to the individual data points and IQR at the different time points. p-values for significant differences were determined using the Wilcoxon rank sum test with continuity correction and are represented. All data are background-subtracted.

Mentions: We also characterized the differentiation stages of the responding HIV-1-specific CD4 and CD8 T cells into T central memory (TCM: CD45RA- CCR7+), T effector memory (TEM: CD45RA- CCR7-) or terminally differentiated T effector memory (TEMRA: CD45RA+ CCR7-) populations as previously described [21]. HIV-1-specific CD4 T cell responses were mostly of TEM phenotype prior to immunization in both vaccinees and placebos and the percentage of CD4+ T cells with TEM phenotype in placebo group was significantly higher than in vaccines (p = 0.022) but only in MVA-B recipients the proportion of this population significantly enhanced (about 3-fold) over time (Fig 7A). Furthermore, the pre-existing HIV-1-specific CD8 T cell responses were mostly of TEM phenotype and to a lesser extent of TEMRA phenotype in both the vaccinee and placebo arms but were unchanged post-vaccination (Fig 7B).


A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART.

Gómez CE, Perdiguero B, García-Arriaza J, Cepeda V, Sánchez-Sorzano CÓ, Mothe B, Jiménez JL, Muñoz-Fernández MÁ, Gatell JM, López Bernaldo de Quirós JC, Brander C, García F, Esteban M - PLoS ONE (2015)

Phenotype of the HIV-1-specific CD4 and CD8 T cell responses.Frequencies of HIV-1-specific CD4 (A) and CD8 T cells (B) (directed against Env+Gag+GPN) with phenotype T central memory (TCM: CD45RA- CCR7+), T effector memory (TEM: CD45RA- CCR7-) or terminally differentiated T effector memory (TEMRA: CD45RA+ CCR7-), in vaccinees and placebos before vaccination (W0), after two (W6) or three (W18) MVA-B or placebo doses or at time of HAART interruption (W24). The boxes correspond to the individual data points and IQR at the different time points. p-values for significant differences were determined using the Wilcoxon rank sum test with continuity correction and are represented. All data are background-subtracted.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4636254&req=5

pone.0141456.g007: Phenotype of the HIV-1-specific CD4 and CD8 T cell responses.Frequencies of HIV-1-specific CD4 (A) and CD8 T cells (B) (directed against Env+Gag+GPN) with phenotype T central memory (TCM: CD45RA- CCR7+), T effector memory (TEM: CD45RA- CCR7-) or terminally differentiated T effector memory (TEMRA: CD45RA+ CCR7-), in vaccinees and placebos before vaccination (W0), after two (W6) or three (W18) MVA-B or placebo doses or at time of HAART interruption (W24). The boxes correspond to the individual data points and IQR at the different time points. p-values for significant differences were determined using the Wilcoxon rank sum test with continuity correction and are represented. All data are background-subtracted.
Mentions: We also characterized the differentiation stages of the responding HIV-1-specific CD4 and CD8 T cells into T central memory (TCM: CD45RA- CCR7+), T effector memory (TEM: CD45RA- CCR7-) or terminally differentiated T effector memory (TEMRA: CD45RA+ CCR7-) populations as previously described [21]. HIV-1-specific CD4 T cell responses were mostly of TEM phenotype prior to immunization in both vaccinees and placebos and the percentage of CD4+ T cells with TEM phenotype in placebo group was significantly higher than in vaccines (p = 0.022) but only in MVA-B recipients the proportion of this population significantly enhanced (about 3-fold) over time (Fig 7A). Furthermore, the pre-existing HIV-1-specific CD8 T cell responses were mostly of TEM phenotype and to a lesser extent of TEMRA phenotype in both the vaccinee and placebo arms but were unchanged post-vaccination (Fig 7B).

Bottom Line: MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1-specific CD8 T cell responses.In addition, vaccination also triggered preferential CD8+ T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses.MVA-B vaccination represents a feasible strategy to improve T cell responses in individuals with pre-existing HIV-1-specific immunity.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.

ABSTRACT

Trial design: Previous studies suggested that poxvirus-based vaccines might be instrumental in the therapeutic HIV field. A phase I clinical trial was conducted in HIV-1-infected patients on highly active antiretroviral therapy (HAART), with CD4 T cell counts above 450 cells/mm3 and undetectable viremia. Thirty participants were randomized (2:1) to receive either 3 intramuscular injections of MVA-B vaccine (coding for clade B HIV-1 Env, Gag, Pol and Nef antigens) or placebo, followed by interruption of HAART.

Methods: The magnitude, breadth, quality and phenotype of the HIV-1-specific T cell response were assayed by intracellular cytokine staining (ICS) in 22 volunteers pre- and post-vaccination.

Results: MVA-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses (mostly against Gag, Pol and Nef antigens) that were high in magnitude, broadly directed and showed an enhanced polyfunctionality with a T effector memory (TEM) phenotype, while maintaining the magnitude and quality of the pre-existing HIV-1-specific CD8 T cell responses. In addition, vaccination also triggered preferential CD8+ T cell polyfunctional responses to the MVA vector antigens that increase in magnitude after two and three booster doses.

Conclusion: MVA-B vaccination represents a feasible strategy to improve T cell responses in individuals with pre-existing HIV-1-specific immunity.

Trial registration: ClinicalTrials.gov NCT01571466.

No MeSH data available.


Related in: MedlinePlus