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Therapeutic TriMix / mRNA based Vaccine in Chronic HIV-1 Infected Patients Receiving Antiretroviral Therapy

Objective

To find a therapy alternative to cART for life is one of the hot topics of investigation in HIV field. Therapeutic vaccination seems to be the best option. We have reported in a double-blind placebo controlled study some of the best, most solid data showing that HIV-1 specific immune responses elicited by therapeutic dendritic cell (DC) vaccines pulsed ex vivo with inactivated autologous whole virus could significantly change pVL set-point (mean peak drop of -1.2 log10 copies/ml). Similar efficacy has been found in a preliminary non controlled clinical trial using DC electroporated with mRNA encoding autologous HIV-1 antigens. However, the logistics of developing a specific vaccine by ex vivo manipulating autologous DC for each patient may be prohibitive. Therefore, we propose that in vivo targeting of DC by direct administration of a rational designed HIV mRNA encoding immunomodulating proteins might be an attractive alternative to target DCs in situ. Our candidate is highly innovative: 1. It is a mRNA based immunogen: it is expected to have a good safety profile, it is classified as nongene therapy by the American and German authorities, is easier to produce and to store regardless of the encoded antigen and is not restricted to a defined HLA type of individuals. 2. The HIV antigen encoded by mRNA has been selected with a rational design: based on our previous works selecting viral targets of protective HIV-1 specific T cell responses in 3 large cohorts of HIV infected individuals. 3. The candidate includes TriMix to target DC in vivo: our data suggest that mRNA encoding a mixture of antigen presenting cells activation molecules (CD40L, a constitutive active variant of TLR4 and CD70) significantly enhanced the induction of antigen-specific T cells. If this candidate would be able to obtain the functional cure in at least a proportion of patients it could be applicable to developing countries and would improve the care and cost of HIV infection.

Field of science

  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /medical and health sciences/basic medicine/pharmacology and pharmacy/pharmaceutical drug/vaccines

Call for proposal

FP7-HEALTH-2013-INNOVATION-1
See other projects for this call

Funding Scheme

CP-FP - Small or medium-scale focused research project

Coordinator

CONSORCI INSTITUT D'INVESTIGACIONS BIOMEDIQUES AUGUST PI I SUNYER
Address
Calle Rossello 149 Puerta Bjs
08036 Barcelona
Spain
Activity type
Other
EU contribution
€ 1 114 220
Administrative Contact
Rosa Vilavella I Gasull (Dr.)

Participants (7)

PRINS LEOPOLD INSTITUUT VOOR TROPISCHE GENEESKUNDE
Belgium
EU contribution
€ 798 560
Address
Nationalestraat 155
2000 Antwerpen
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Nadine Van Peer (Ms.)
VRIJE UNIVERSITEIT BRUSSEL
Belgium
EU contribution
€ 303 220
Address
Pleinlaan 2
1050 Brussel
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Nik Claesen (Prof.)
ETHERNA IMMUNOTHERAPIES
Belgium
EU contribution
€ 1 718 520
Address
Galileilaan 19
2845 Niel
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Hilde Van Raemdonck (Mrs.)
ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
Netherlands
EU contribution
€ 932 800
Address
Dr Molewaterplein 40
3015 GD Rotterdam
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Wim Leep (Mr.)
FUNDACIO PRIVADA INSTITUT DE RECERCA DE LA SIDA-CAIXA
Spain
EU contribution
€ 648 200
Address
Carretera De Canyet
08916 Barcelona
Activity type
Research Organisations
Administrative Contact
Lourdes Grau (Ms.)
SYNAPSE RESEARCH MANAGEMENT PARTNERS SL
Spain
EU contribution
€ 308 800
Address
Calle Velazquez 94 Planta 1
28006 Madrid
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Sandra Pla (Ms.)
ASPHALION SL
Spain
EU contribution
€ 160 400
Address
Calle Tarragona, Numeros 151-157, Planta 10, Bloqu
08014 Barcelona
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Montse Perez (Mrs.)