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Next Generation HIV-1 Immunogens inducing broadly reactive Neutralising antibodies

Objective

The elicitation of broadly neutralising antibodies (Nab) remains the primary and most challenging goal in HIV-1 vaccine development. Although a few anti-HIV-1 monoclonal antibodies with broadly neutralising capability have been isolated from infected individuals, none of the immunization strategies thus far explored has proven effective in inducing similar antibodies. Objective of this application is the development of a variety of ‘next-generation’ HIV-1 envelope-based immunogens that in combination with new adjuvant formulations are capable of eliciting high-titer broadly Nab responses. Our strategy will be based on one side on the identification and cloning of envelopes that have successfully elicited broad Nabs in their natural hosts, focusing on HIV-1 strains derived from patients with high-titered broad Nabs in their sera; on the other side, we will introduce rational modifications into these and promising HIV-env based immunogens that are already under development by NGIN’s partners, with the aim of exposing cryptic conserved neutralization epitopes and permitting their efficient presentation to the immune system. HIV-1 envelopes will be expressed in viral vectors or as trimeric (gp150) soluble proteins and screened for their immunogenicity and antigenicity in rabbits. A selection of envelopes with highest antigenicity will be expressed as trimeric envelope-complexes on the surface of virosomes or virus-like particles (VLP), to further improve immunogenicity. New immunogens will be evaluated in prime-boost regimens in rabbits using novel effective adjuvant formulations. Immunogen/adjuvant combinations that prove most effective in eliciting broadly Nabs both systemically and at the mucosal level will be evaluated in non-human primates for their immunogenicity and efficacy upon challenge with live heterologous virus. Finally, formulations that will elicit protective immunity in non-human primates will be forwarded for proof-of-principle testing in humans.

Call for proposal

FP7-HEALTH-2007-A
See other projects for this call

Funding Scheme

CP-IP - Large-scale integrating project

Coordinator

UNIVERSITA VITA-SALUTE SAN RAFFAELE
Address
Via Olgettina 58
20132 Milano
Italy
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 76 476,57
Administrative Contact
Maria Rosa Pedrazzi (Dr.)

Participants (17)

ACADEMISCH MEDISCH CENTRUM BIJ DE UNIVERSITEIT VAN AMSTERDAM
Netherlands
EU contribution
€ 488 756
Address
Meibergdreef 15
1105AZ Amsterdam
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Erik Veenstra (Mr.)
MEDICAL RESEARCH COUNCIL

Participation ended

United Kingdom
EU contribution
€ 224 197,45
Address
North Star Avenue Polaris House 2 Floor David Phillips Building
SN2 1FL Swindon
Activity type
Research Organisations
Administrative Contact
Atul Kotecha (Dr.)
ISTITUTO NAZIONALE TUMORI Fondazione Pascale
Italy
EU contribution
€ 269 167
Address
Via Mariano Semmola 142
80131 Napoli
Activity type
Research Organisations
Administrative Contact
Vincenza Farinari (Dr.)
CYTOS BIOTECHLOLOGY AG
Switzerland
EU contribution
€ 303 866
Address
Waggistrasse, 25
8952 Zurich-schlieren
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Philippe Saudan (Dr.)
UNIVERSITA DEGLI STUDI DI MILANO
Italy
EU contribution
€ 337 120
Address
Via Festa Del Perdono 7
20122 Milano
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Alessandro Cavallina (Dr.)
AVARIS AB
Sweden
EU contribution
€ 219 056
Address
C/o Karolisnka Innovations Ab, Fogdevreten 2B
17177 Stockholm
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Jonny Greinsmark (Mr.)
STATENS SERUM INSTITUT
Denmark
EU contribution
€ 436 027
Address
Artillerivej 5
2300 Kobenhavn S
Activity type
Research Organisations
Administrative Contact
Vibeke Lund Fonsholt (Dr.)
COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES
France
EU contribution
€ 946 634
Address
Rue Leblanc 25
75015 Paris 15
Activity type
Research Organisations
Administrative Contact
Nathalie Le-Gouzouguec (Dr.)
KAROLINSKA INSTITUTET
Sweden
EU contribution
€ 1 027 944
Address
Nobels Vag 5
17177 Stockholm
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Hedde Lundgren (Ms.)
PRINS LEOPOLD INSTITUUT VOOR TROPISCHE GENEESKUNDE
Belgium
EU contribution
€ 397 920
Address
Nationalestraat 155
2000 Antwerpen
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Nancy Janssens (Ms.)
MYMETICS SA
Switzerland
EU contribution
€ 28 071,27
Address
Route De La Corniche 4
1066 Epalinges
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Carmelina Mahrer (Ms.)
MAX IV Laboratory, Lund University
Sweden
EU contribution
€ 481 360
Address
Paradisgatan 5C
22100 Lund
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Anette Welin (Ms.)
UNIVERSITE PARIS DESCARTES
France
EU contribution
€ 484 666
Address
Rue De L Ecole De Medecine 12
75270 Paris Cedex 06
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Stephan Sirven (Mr.)
Public Health England an Executive Agency of the Dept of Health
United Kingdom
EU contribution
€ 381 976
Address
Waterloo Road
SE1 8UG London
Activity type
Research Organisations
Administrative Contact
Deborah Smith (Ms.)
THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
EU contribution
€ 176 733,55
Address
Wellington Square University Offices
OX1 2JD Oxford
Activity type
Higher or Secondary Education Establishments
Administrative Contact
Stephen Conway (Dr.)
FONDAZIONE CENTRO SAN RAFFAELE DEL MONTE TABOR
Italy
EU contribution
€ 1 254 771,16
Address
Via Olgettina 60
20132 Milano
Activity type
Research Organisations
Administrative Contact
Maria Rosa Pedrazzi (Dr.)
OSPEDALE SAN RAFFAELE SRL
Italy
Address
Via Olgettina 60
20132 Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Administrative Contact
Maria Rosa Pedrazzi (Dr.)