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Next Generation HIV-1 Immunogens inducing broadly reactive Neutralising antibodies

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.

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)

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Academisch Medisch Centrum bij de Universiteit van Amsterdam

Netherlands

EU Contribution

€ 488 756

MEDICAL RESEARCH COUNCIL

United Kingdom

EU Contribution

€ 224 197,45

ISTITUTO NAZIONALE TUMORI Fondazione Pascale

Italy

EU Contribution

€ 269 167

CYTOS BIOTECHLOLOGY AG

Switzerland

EU Contribution

€ 303 866

UNIVERSITA DEGLI STUDI DI MILANO

Italy

EU Contribution

€ 337 120

AVARIS AB

Sweden

EU Contribution

€ 219 056

STATENS SERUM INSTITUT

Denmark

EU Contribution

€ 436 027

COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES

France

EU Contribution

€ 946 634

KAROLINSKA INSTITUTET

Sweden

EU Contribution

€ 1 027 944

PRINS LEOPOLD INSTITUUT VOOR TROPISCHE GENEESKUNDE

Belgium

EU Contribution

€ 397 920

MYMETICS SA

Switzerland

EU Contribution

€ 28 071,27

LUNDS UNIVERSITET

Sweden

EU Contribution

€ 481 360

UNIVERSITE PARIS DESCARTES

France

EU Contribution

€ 484 666

Public Health England an Executive Agency of the Dept of Health

United Kingdom

EU Contribution

€ 381 976

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

United Kingdom

EU Contribution

€ 176 733,55

Fondazione Centro San Raffaele

Italy

EU Contribution

€ 1 254 771,16

OSPEDALE SAN RAFFAELE SRL

Italy

Project information

Grant agreement ID: 201433

Status

Closed project

  • Start date

    1 February 2008

  • End date

    31 July 2012

Funded under:

FP7-HEALTH

  • Overall budget:

    € 10 148 011,56

  • EU contribution

    € 7 534 742

Coordinated by:

UNIVERSITA VITA-SALUTE SAN RAFFAELE

Italy