INTEGRATED PROJECTINTEGRATED PROJECT

MUCOSAL VACCINES FOR POVERTY-RELATED DISEASESMUCOSAL VACCINES FOR POVERTY-RELATED DISEASES

MUVAPREDMUVAPREDMUCOSAL VACCINES FOR POVERTY-RELATED DISEASESMUCOSAL VACCINES FOR POVERTY-RELATED DISEASES

MUVAPREDMUVAPRED

Project SummaryProject Summary

Human Immunodeficiency Virus and Human Immunodeficiency Virus and Mycobacterium Mycobacterium

tuberculosistuberculosis enter the human body at mucosal sites. The aim enter the human body at mucosal sites. The aim

of the present project is to develop mucosally delivered of the present project is to develop mucosally delivered

vaccines against HIV and TB which will induce local immunity vaccines against HIV and TB which will induce local immunity

able to neutralise the pathogens at their port of entry and able to neutralise the pathogens at their port of entry and

systemic immunity able to prevent systemic spread of the systemic immunity able to prevent systemic spread of the

infection. The possible development of mucosal vaccines infection. The possible development of mucosal vaccines

against malaria will be also investigated. The trust of the against malaria will be also investigated. The trust of the

project derives from the recent proof of concept that mucosal project derives from the recent proof of concept that mucosal

vaccines are feasible in humans. vaccines are feasible in humans.

While the first trials are performed, new systems to deliver While the first trials are performed, new systems to deliver

mucosal vaccines and basic mechanisms of mucosal immune mucosal vaccines and basic mechanisms of mucosal immune

responses and memory in humans will be studied. This will responses and memory in humans will be studied. This will

allow better understanding of the clinical results and allow better understanding of the clinical results and

optimisation of second generation vaccines to be tested in optimisation of second generation vaccines to be tested in

Developing Countries during the second phase of the project.Developing Countries during the second phase of the project.

Phase I trialsPhase I trialsin EUin EU

Phase I trials inPhase I trials inAfricaAfrica

Vaccine Vaccine candidatescandidates

Antigens AdjuvantsDelivery systems

Pre-clinical testingPre-clinical testing

Mice

Guinea Pigs (TB)

Monkeys

Vaccine Vaccine candidates candidates for EDCTPfor EDCTP

New vaccines for povertyNew vaccines for poverty

MUVAPREDMUVAPRED

Project structureProject structure

Development of new promising vaccine candidates (Subproject 1)

1 2 3 4 5 YEARS

Indicative timelines of the main activities

Development of new promising vaccine candidates

  Comparative testing in animal models

Phase I trials in EU with available candidates

Clinical trials in Africa

Phase I clinical trials with new vaccine candidates

Correlates of protection

web site: http://www.mucosalimmunity.org/muvapred/web site: http://www.mucosalimmunity.org/muvapred/

Project coordinator: R. Rappuoli, Chiron Srl Project coordinator: R. Rappuoli, Chiron Srl EC contribution : 15.250.000 EuroEC contribution : 15.250.000 EuroStarting date: 1st December 2003Starting date: 1st December 2003Duration: 5 yearsDuration: 5 yearsParticipants: 24 from 10 countriesParticipants: 24 from 10 countries

ObjectivesObjectives

• Phase I clinical trials in EuropePhase I clinical trials in Europe with the available mucosal antigens against HIV/AIDS and TB (two to three vaccine candidates).

• Second generation, optimised vaccine candidatesSecond generation, optimised vaccine candidates against HIV/AIDS, TB and malaria (antigens, adjuvants, delivery systems).

• Selection of the most promising vaccine candidatesmost promising vaccine candidates by comparative testing in animal models

• Phase I clinical trials in Europe with new vaccine candidatesPhase I clinical trials in Europe with new vaccine candidates developed by the consortium

• Phase I clinical trials in AfricaPhase I clinical trials in Africa with the vaccine candidates that have proven to be safe and immunogenic in the first clinical trials in Europe

ParticipantsParticipantsChiron Italy, Imperial College of Science UK, University of Goteborg Sweden, University of Siena Italy, Institute Pasteur France, Istituto Superiore di Sanità Italy, Institute for Research in Biomedicine CH, Max-Planck-Institute, Germany University Hamburg Germany,Trinity College Dublin Ireland, Serum State Institute Denmark, Consiglio Nazionale delle Ricerche Italy, Istituto Humanitas Milano Italy, German Arthritis Research Center DRFZ Germany, St George’s Vaccine Institute UK, Institute of Microbiology Czech Republic, CAMR UK, University of Florence Italy, Centre-Hospitalier-Universitaire Ignace Deen Guinea, University of Lausanne Switzerland, ALTA Srl Italy, LIONEX Diagnostic & Therapeutics GmbH Germany, INOTECH AG Switzerland

Antigens

WP1

Adjuvants

WP2

Delivery

systems

WP3

Sub-project 1

Vaccine CandidatesVaccine Candidates

Mice

WP4

Guinea

WP5

Monkeys

WP6

Sub-project 2

Animal studiesAnimal studies

Correlates

protection

WP7

GMP

WP8

Phase I

WP9

Sub-project 3

Human studiesHuman studies

MUVAPREDMUVAPRED

Scientific and Administrative Management

COORDINATING TEAM COORDINATING TEAM

STEERING STEERING COMMITTEECOMMITTEE

R. Rappuoli

D. Medaglini

EU Sci. Officer

P. Andersen

G. Dougan

J. Holmgren

S.H.E. Kaufmann

A. Lanzavecchia

D. Lewis T. Lehner

G. Pozzi

R. Rappuoli, Chiron R. Rappuoli, Chiron Project Coordinator

D. Medaglini D. Medaglini University of SienaScientific Manager

A. Tagliabue, ALTA A. Tagliabue, ALTA Administrative Manager

EXTERNAL EXTERNAL ADVISORYADVISORYBOARDBOARD