Abstract
Trial DesignPrevious 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.MethodsThe 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.ResultsMVA-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.ConclusionMVA-B vaccination represents a feasible strategy to improve T cell responses in individuals with pre-existing HIV-1-specific immunity.Trial RegistrationClinicalTrials.gov NCT01571466
Highlights
Active antiretroviral therapy (HAART) has dramatically improved the clinical outcome in human immunodeficiency virus (HIV)-infected individuals through sustained suppression of viral replication [1]
Modified Vaccinia Virus Ankara (MVA)-B vaccine induced newly detected HIV-1-specific CD4 T cell responses and expanded pre-existing responses 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-1specific CD8 T cell responses
We have previously shown that an MVA vector expressing the HIV-1 Env, Gag, Pol and Nef antigens from clade B was safe and broadly immunogenic when tested in a phase I clinical trial in human healthy volunteers, inducing broad, polyfunctional and long-lasting HIV-1-specific CD4 and CD8 T cell responses, as well as humoral responses against Env in most of the vaccinees [12, 13]
Summary
Active antiretroviral therapy (HAART) has dramatically improved the clinical outcome in human immunodeficiency virus (HIV)-infected individuals through sustained suppression of viral replication [1]. Therapeutic HIV-1 vaccination is one approach that could potentially achieve these goals through the stimulation of effective HIV-1-specific T cell responses; primarily cytolytic/virus suppressive CD8 T cells with supporting CD4 T help [7,8,9,10,11]. Attenuated poxviruses such as canarypox, fowlpox, NYVAC and Modified Vaccinia Virus Ankara (MVA) have been applied in several therapeutic HIV-1 vaccination trials with encouraging results in terms of activation of HIV-1-specific T cell responses, but the outcomes of viral load reduction after HAART interruption have been quite discrepant (for review [11])
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