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Dendritic Cell-Based Vaccines

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Mishma:
Dendritic cells present antigens to naive T cells in our lymph glands. This would be especially important to newly infected patients who have immediately started cART, before the "architecture" of the gland was altered with long term chronic HIV infection.


RESEARCH ARTICLE
HIV
A Dendritic Cell–Based Vaccine Elicits T Cell Responses Associated with Control of HIV-1 Replication
Felipe García1,*,†, Nuria Climent1,*, Alberto C. Guardo1, Cristina Gil1, Agathe León1, Brigitte Autran2, Jeffrey D. Lifson3, Javier Martínez-Picado4,5, Judit Dalmau4, Bonaventura Clotet4, Josep M. Gatell1, Montserrat Plana1,*, Teresa Gallart1,*, For the DCV2/MANON07-ORVACS Study Group
+ Author Affiliations

http://stm.sciencemag.org/content/5/166/166ra2.abstract

1Hospital Clinic-IDIBAPS, HIVACAT, University of Barcelona, 08036 Barcelona, Spain.
2INSERM UMR-S-945, Université Paris-VI Pierre-et-Marie-Curie, Hôpital Pitié-Salpêtrière, 75013 Paris, France.
3AIDS and Cancer Virus Program, SAIC-Frederick Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
4AIDS Research Institute IrsiCaixa, Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, 08916 Badalona, Spain.
5Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain.
+ Author Notes

↵* These authors contributed equally to this work.

↵†To whom correspondence should be addressed. E-mail: fgarcia@clinic.ub.es
ABSTRACT

Combination antiretroviral therapy (cART) greatly improves survival and quality of life of HIV-1–infected patients; however, cART must be continued indefinitely to prevent viral rebound and associated disease progression. Inducing HIV-1–specific immune responses with a therapeutic immunization has been proposed to control viral replication after discontinuation of cART as an alternative to “cART for life.” We report safety, tolerability, and immunogenicity results associated with a control of viral replication for a therapeutic vaccine using autologous monocyte-derived dendritic cells (MD-DCs) pulsed with autologous heat-inactivated whole HIV. Patients on cART with CD4+ >450 cells/mm3 were randomized to receive three immunizations with MD-DCs or with nonpulsed MD-DCs. Vaccination was feasible, safe, and well tolerated and shifted the virus/host balance. At weeks 12 and 24 after cART interruption, a decrease of plasma viral load setpoint ≥1 log was observed in 12 of 22 (55%) versus 1 of 11 (9%) and in 7 of 20 (35%) versus 0 of 10 (0%) patients in the DC–HIV-1 and DC-control groups, respectively. This significant decrease in plasma viral load observed in immunized recipients was associated with a consistent increase in HIV-1–specific T cell responses. These data suggest that HIV-1–specific immune responses elicited by therapeutic DC vaccines could significantly change plasma viral load setpoint after cART interruption in chronic HIV-1–infected patients treated in early stages. This proof of concept supports further investigation of new candidates and/or new optimized strategies of vaccination with the final objective of obtaining a functional cure as an alternative to cART for life.

Jmarksto:
Even though the results are short term, these findings seem significant in my mind for a few reasons:

1.) Isn't this the first vaccine to show this much of an impact on viral load across more than 50% of participants for any period of time?  The RV144 trial had a 30% effectiveness, after significant analysis.  I recognize this is a phase I study with 60 participants and the RV 144 study was a phase II study with 16,000 participants - so they are at least two different kinds of apples, but not apples and oranges.

2.) These are the first preliminary efficacy findings of using the whole killed virus rather than a viral vector.  The University of Western Ontario and Sumagen's approach (SAV001) also uses a whole killed virus (but I don't think published phase I efficacy numbers).

It'll be interesting to see where this goes over the next few years.

JM



hiv_positive_BG:
Hello, I hope my question doesn't sound naive, but how could one benefit from that new discovery? If you go to that hospital in Spain, could you also become a "test patient", who would benefit from one year free of medications?

I live in Bulgaria and wonder could I go to Spain and get the "one year off" vaccine...

Mishma:
Here in the US we have a portal to clinical trials throughout the US via the internet ( http://www.clinicaltrials.gov). I do not know how they do their recruiting anywhere else.

This was a small proof of concept study. Given their results it is sure to be expanded. You could contact the authors of this study and tell them you are interested in becoming a study participant.

There are a number of Brits on these boards, I bet they would know better how things work in the EU.   

hiv_positive_BG:
Thanks a lot for your answer!

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