Viimeiset uutiset Nef- virusfaktoritutkimuksista

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HIV-1 Nef (2066 vastausta)

• (1)

http://www.ncbi.nlm.nih.gov/pubmed/22194689

• (2) Toinen vastaus sisältää raportin rokotteesta, joka on kliinisessä vaiheessa:

• ROKOTE sisältää myös Nef antigeenia!

Clin Immunol. 2011 Nov 16. [Epub ahead of print]

A phase I/IIa immunotherapy trial of HIV-1-infected patients with Tat, Rev and Nef expressing dendritic cells followed by treatment interruption.

Allard SD, De Keersmaecker B, de Goede AL, Verschuren EJ, Koetsveld J, Reedijk ML, Wylock C, De Bel AV, Vandeloo J, Pistoor F, Heirman C, Beyer WE, Eilers PH, Corthals J, Padmos I, Thielemans K, Osterhaus AD, Lacor P, der Ende ME, Aerts JL, van Baalen CA, Gruters RA.

Source

Department of Internal Medicine and Infectious Diseases, Universitair Ziekenhuis Brussel, Brussels, Belgium; Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Brussels, Belgium.

Abstract

In a phase I/IIa clinical trial, 17 HIV-1 infected patients, stable on cART, received 4 vaccinations with autologous dendritic cells electroporated with mRNA encoding Tat, Rev and Nef, after which cART was interrupted.

Vaccination was safe and feasible. During the analytical treatment interruption (ATI), no serious adverse events were observed.

Ninety-six weeks following ATI, 6/17 patients remained off therapy.

Although induced and/or enhanced CD4(+) and CD8(+) T-cell responses specific for the immunogens were observed in most of the patients, we found no correlation with the number of weeks off cART.

Moreover, CD4(+) T-cell counts, plasma viral load and the time remaining off cART following ATI did not differ from historical control data.

To conclude, the vaccine was safe, well tolerated and resulted in vaccine-specific immune responses.

Since no correlation with clinical parameters could be found, these results warrant further research in order to optimize the efficacy of vaccine-induced T-cell responses.

Copyright © 2011 Elsevier Inc. All rights reserved.

PMID:

22177848

[PubMed - as supplied by publisher]

• (3) Myös tieto rokotekokeilusta

AIDS. 2011 Dec 7. [Epub ahead of print]

mRNA-based dendritic cell vaccination induces potent antiviral T-cell responses in HIV-1-infected patients.

Van Gulck E, Vlieghe E, Vekemans M, Van Tendeloo VF, Van De Velde A, Smits E, Anguille S, Cools N, Goossens H, Mertens L, De Haes W, Wong J, Florence E, Vanham G, Berneman ZN.

Source

aDepartment of Biomedical Sciences, Division of Microbiology, Virology Unit, Institute of Tropical Medicine, Antwerp, Belgium bDepartment of Clinical Sciences, Medical Service, HIV and STD Unit, Institute of Tropical Medicine, Antwerp, Belgium cVaccine and Infectious Disease Institute, Faculty of Medicine, University of Antwerp, Antwerp, Belgium dCenter for Cell Therapy and Regenerative Medicine (CCRG) and Division of Hematology, Antwerp University Hospital (UZA), Edegem, Belgium eDepartement of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA fFaculty of Pharmaceutical, Biomedical Sciences and Veterinary Sciences, University of Antwerp, Antwerp and Faculty of Medicine and Pharmacy, Free University of Brussels (VUB), Brussels, Belgium. 1Contributed equally as first authors. 2Contributed equally as senior authors.

Abstract

BACKGROUND:

In an effort to raise protective antiviral immunity, dendritic cell (DC) immunotherapy was evaluated in 6 adults infected with human immunodeficiency virus (HIV)-1 and stable under antiretroviral therapy (HAART).

DESIGN & METHODS:

Autologous monocyte-derived DC electroporated with mRNA encoding Gag and a chimeric Tat-Rev-Nef protein were administered, while patients remained on HAART. Feasibility, safety, immunogenicity and antiviral responses were investigated.

RESULTS:

DC vaccine preparation and administration were successful in all patients and only mild adverse events were seen. There was a significant increase post-DC as compared to pre-DC vaccination in magnitude and breadth of HIV-1-specific interferon (IFN)-γ response, in particular to Gag, and in T-cell proliferation. Breadth of IFN-γ response and T-cell proliferation were both correlated with CD4+ and CD8+ polyfunctional T-cell responses. Importantly, DC vaccination induced or increased the capacity of autologous CD8+ T-cells to inhibit superinfection of CD4+ T-cells with the vaccine-related IIIB virus and some but not all other HIV-1 strains tested. This HIV-1-inhibitory activity, indicative of improved antiviral response, was correlated with magnitude and breadth of Gag-specific IFN-γ response.

CONCLUSIONS:

Therapeutic immunization with DC was safe and successful in raising antiviral cellular immune responses, including effector CD8+ T-cells with virus inhibitory activity. The stimulation of those potent immunological and antiviral effects, which have been associated with control of HIV-1, underscores the potential of DC vaccination in the treatment of HIV-1. The incomplete nature of the response in some patients helped to identify potential targets for future improvement, i.e. increasing antigenic spectrum and enhancing T-cell response.

PMID:

22156965

[PubMed - as supplied by publisher]

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