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Amplified antigen-specific immune responses in HIV-1 infected individuals in a double blind DNA immunization and therapy interruption trial

Gudmundsdotter, Lindvi and Wahren, Britta and Haller, B. Kristian and Boberg, Andreas and Edbäck, Ulrika and Bernasconi, D. and Buttò, Stefano and Gaines, Hans and Imami, Nesrina and Gotch, Frances M. and Lori, Franco and Lisziewicz, Julianna and Sandström, E. and Hejdeman, B. (2011) Amplified antigen-specific immune responses in HIV-1 infected individuals in a double blind DNA immunization and therapy interruption trial. Vaccine, Vol. 29 (33), p. 5558-5566. eISSN 1873-2518. Article.

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DOI: 10.1016/j.vaccine.2011.01.064

Abstract

Immunotherapy in patients with HIV-1 infection aims to restore and broaden immunological competence, reduce viral load and thereby permit longer periods without combined antiretroviral treatment (cART). Twelve HIV-1-infected patients on cART were immunized on the skin with DNA plasmids containing genes of several HIV-1 subtypes with or without the addition of hydroxyurea (HU), or with placebo. The mean net gain of HIV-specific CD8+ T cell responses were higher and broader in the HIV DNA vaccine groups compared to non-vaccinated individuals (p < 0.05). The vaccine-induced immune responses per se had no direct effect on viral replication. In all patients combined, including placebo, the viral set point after a final structured therapy interruption (STI) was lower than prior to initiation of cART (p = 0.003). Nadir CD4 levels appeared to strongly influence the post-STI viral titers. After the sixth immunization or placebo, patients could stay off cART for a median time of 15 months. The study shows that HIV DNA immunization induces broader and higher magnitudes of HIV-specific immune responses compared to structured therapy interruptions alone. Although compromised by small numbers of patients, the study also demonstrates that well-monitored STI may safely function as an immunological read out of HIV vaccine efficacy.

Item Type:Article
ID Code:5733
Status:Published
Refereed:Yes
Uncontrolled Keywords:HIV-1, transdermal therapeutic immunization, DNA vaccine
Subjects:Area 06 - Scienze mediche > MED/17 Malattie infettive
Divisions:002 Altri enti e centri di ricerca del Nord Sardegna > ViroStatics, Sassari
Publisher:Elsevier
eISSN:1873-2518
Copyright Holders:© 2011 Published by Elsevier
Deposited On:26 May 2011 13:26

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