Keywords: HIV; therapeutic vaccine; apoptosis
With both more than 40 million people living with HIV and the continuous spread of the virus, there is not only an urgent need to develop an effective prophylactic vaccine, but also a vital requirement for novel therapies with long-lasting effect. Therapeutic vaccination could be one way of achieving this. The overall objective for this multidisciplinary consortium is to transfer a novel therapeutic HIV-1 vaccine concept to the clinic. The concept is based on the consortium’s basic discovery that genes can be horizontally transferred to neighbouring cells by the uptake of apoptotic cells. The uptake of apoptotic cells also allows transfer of proteins leading to cross-presentation of antigens. The aim of this project is to develop a therapeutic HIV-1 vaccine (acronym Auto/AlloCell-HIV) based on this technology.
Apoptotic cells can function as a good antigen delivery system by utilising the body’s own natural mechanisms for transfer of DNA and proteins to antigen presenting cells (APC). Normally during HIV-1 infection this system is hindered by multiple mechanisms. It is therefore envisaged using this system during periods of low viral replication achieved by antiretroviral treatment. Hence, we will immunise already infected individuals who have received a limited period of antiretroviral treatment with either autologous apoptotic HIV-1 infected cells (acronym AutoCell-HIV) or allogeneic apoptotic HIV-1 DNA containing cells (acronym AlloCell-HIV).
Taking into consideration the obstacles of developing a prophylactic HIV-1 vaccine, such as the scientific challenges, the time schedules involved and the devastating HIV-1 epidemic, the aim is instead to develop a therapeutic vaccine. The limitations ( e.g.severe side effects, life-long treatment, development of resistance, no cure and the cost) of current anti-retroviral drugs justify the search for novel therapies that would protect the infected individual from developing AIDS. The development of a therapeutic vaccination strategy, which could help to contain viral replication, would also potentially allow for decreased transmission and have a beneficial effect on the HIV-1 epidemic. An autologous carrier of viral genes could theoretically be the solution to several of the problems associated with the various vaccine candidates tested so far.
Safety issues are minimal and so is the risk for immunological reactions to the vector carrying the vaccine. Anti-retroviral treatment (ART) leads to reconstitution of immune responses to many pathogens but without the emergence of HIV-specific responses. Anti-retroviral treatment also allows patients to respond to immunisation using recall antigens and neo-antigens. Hence, it may be feasible to induce a novel adaptive HIV-1-specific immune response by therapeutic vaccination that would also allow the patient to stop anti-retroviral medication. An individualised vaccine composition could potentially include the patient’s own HIV-1 genes and enhance the possibility of generating HIV-1-specific controlling immunity.
The objective is to develop a therapeutic HIV vaccine using apoptotic cells as the antigen delivery system. To achieve this, the project will carry out the following:
The consortium expects to obtain safety measurements and proof-of-concept in macaques. In addition, GMP compliant production protocols will be developed. If the vaccine is promising in macaques, a phase I/II therapeutic trial will also be initiated.
The technology can be applied for treatment of chronic infections. If feasibility and efficacy in a therapeutic HIV trial can be shown, it will open up the possibility of applying the concept to a preventive HIV vaccine.
|Official Address||Other Information|
|2 ||Gerrit Koopman ||Biomedical Primate Research Center |
Lange Kleiweg 139
NL-2288 GH Rijswijk
|Tel: +31 15284 2660 |
Fax: +31 15284 3986
|3 ||Eva-Maria Fenyo ||Department of Microbiology, Dermatology and Infection |
SE-223 62 Lund
|Tel: +46 46 173275 |
Fax: +46 46 176033
|4 ||Luc Perrin ||Laboratory of Virology |
Geneva University Hospital/Geneva Medical School
Rue Micheli-de-Crest 24
|Tel: +41 22 372 4991 |
Fax: +41 22 372 4990
|5 ||Jan Andersson ||Center for Infectious Medicine, I63 |
Karolinska University Hospital Huddinge
SE-141 86 Stockholm
|Tel: +46 8 5858 2234 |
Fax: +46 8 746 6280
|6 ||Brigitte Autran ||Laboratoire d’Immunologie Cellulaire et Tissulaire |
Universite Pierre et Marie Curie
83 Bld de l’Hôpital
FR-75013 Paris, Cedex 13
|Tel: +33 1 42 17 74 81 |
Fax: +33 1 42 17 74 90