Summary:

The successful development of preventative strategies against HIV-1 infection (microbicides, vaccines or their combined effects) would provide a pivotal turning point in global efforts to combat the pandemic spread of AIDS providing an incalculable impact on solving societal prob-lems associated with this disease. The principal aim of this project is to bring together EU scien-tists from the microbicide and vaccine fields to embrace a co-ordinated approach to HIV-1 infec-tion prevention research. Partners in the EUROPRISE consortium represent 13 projects funded by the European Commission from the sixth Framework Programme as well as four projects funded by the Gates Foundation.

These projects involve 132 institutions from 22 countries. EUROPRISE is, in this respect, the first consortium to purposely bring these groups together in a truly integrated fashion from both within Europe and internationally. EUROPRISE will offer an integrated programme of research; co-ordinate a wide portfolio of activities and encompass the whole pipeline of vaccine and microbicide development; from early discovery, through to early clinical trials. This unique approach places the Network at the international forefront, for understanding the interface between these two technologies; pursuing a critical path to the develop-ment of effective HIV-1 infection prevention strategies.

Background:

Although therapeutics for HIV infection and AIDS continue to improve and initiatives for mak-ing these products available in developing countries have been introduced, ultimately, the global incidence of HIV infection is critically dependent on the development of safe and effec-tive strategies to block and prevent HIV transmission.

The design and implementation of effective microbicide and vaccine strategies, individually and possibly in combination, will be key to achieving this goal. Ideally, microbicides will pro-vide chemical and vaccines immune protection respectively, at the mucosal surfaces of the va-gina and rectum, which represent the major portals of viral entry. The combination of these approaches may maximise potential synergy between both technologies.

It is now well established that under most circumstances, vaccines delivering non-replicating antigens fail to induce sufficient mucosal responses and immunological memory to provide protection against high viral challenge. In contrast, while it may be technically easier to develop microbicides that prevent transmission when applied before intercourse, their duration of protection is likely to be short-lived and their efficacy will be critically dependent upon user compliance. To date, both fields have been slow to work together in the development of products that provide multiple levels of protection. This network is focusing on the premise that microbicides and vaccines that target multiple stages of mucosal transmission will have the best chance of success. Since both target the same proc-esses, there is a clear overlap between the two fields.

Indeed, there are compelling reasons as to why the two fields should work together on develop-ing effective strategies to prevent mucosal vaginal or rectal transmission including:

1. Approximately 80% of new HIV infections are now heterosexual and the main portal of entry is across the vaginal or rectal mucosa. Local immunity at the site of infection is likely to be the most potent form of protection
2. Topically applied products are likely to have a high level of acceptance. Importantly, their use would be female initiated. This is an important factor for women who have no means to protect themselves if their partners do not use male condoms or do not allow female condoms to be used
3. Effective microbicides are likely to be available before effective vaccine candidates. Thus it is highly likely that in the not too distant future all vaccine efficacy trials will be carried out in an environment where there is widespread use of vaginal microbicides. Consequently, it will be important to understand the interaction and potential interface of these different prevention technologies. Furthermore, microbicides, if successfully introduced, may pro-vide an established route for vaginal delivery of formulations designed to stimulate and/or activate protective immunity. The future combination of strategies developed in this pro-gramme - either through crossover of microbicide and vaccine use in common populations or as a result of a deliberate strategy to develop a combined vaccine-microbicide modality - has the potential to maximise the protective effects of both strategies.

Aim:

The successful development of preventative strategies against HIV-1 (microbicides, vaccines or their combined effects) would provide a pivotal turning point in global efforts to combat the pandemic spread of AIDS providing an incalculable impact on solving societal problems asso-ciated with this disease. The principal aim of this proposal is to bring together EU scientists from the microbicide and vaccine fields to embrace a coordinated approach to HIV-1 preven-tion research.

Delivery of the goals will be achieved through the following scientific and technical objectives:

1. Standardisation and harmonisation of research tools
2. Identification of new anti-HIV INFECTION AND AIDS vaccine and microbicide candi-dates and combinations to prevent HIV infection /AIDS
3. Establishment of a clinical development pathway for vaccines and microbicides within a European framework
4. Provision of Scientific training in microbicide and vaccine development
5. To facilitate access to information relevant to HIV-1 microbicides and vaccines
6. Provision of a single focus for European HIV-1 microbicide and vaccine research.

Expected results:

1. Standardisation and harmonisation of research tools as applied to basic, animal and clinical research and related to microbicides and vaccines. Verifiable aspects will be the develop-ment of core protocols, provision of standardised reagents and the establishment of a quality assurance programme
2. The development of a portfolio of existing and new prevention candidates (vaccines, micro-bicides and combinations) that can be evaluated on a one-on-one basis to prioritise the most promising leads for progression into translational clinical research. Verifiable indicators will be the development of an evolving portfolio of prevention candidates and their progress through preclinical evaluation
3. Provision of an accessible toolbox to support the translation of HIV-1 vaccine or microbi-cidal products from basic research in the European Research Area (ERA) into clinical trials. Verifiable indicators will be the accessibility and utility of the translational toolbox
4. The increased integration of European research in the fields of HIV-1 vaccine and microbi-cide research. Verifiable indicators will be seen through workshop, conference attendance, scientific exchange and attainment of high degrees
5. The development of an Internet resource that will be used by EUROPRISE participants and the scientific community. Verifiable indicators will be the utility and maintenance of the EUROPRISE website
6. Effective integration and identity of European microbicide and vaccine research. Verifiable indicators will view: an increase in collaborative research; publications; new joint research proposals; active engagement of community groups; and strong international representation of EU HIV prevention (conferences, expert panels, advisory boards, and publication of con-sensus documents).

Potential applications:

The potential strategic impact on solving societal problems for any project aimed at developing a preventative strategy against HIV infection /AIDS (microbicides or vaccines) is almost incal-culable. HIV infection /AIDS is a global issue and UNAIDS/WHO estimate that at the end of 2004, 40 million people globally were living with HIV, of which 28.5 million were in Sub- Saharan Africa. In Eastern Europe and Central Asia, a rapid increase in HIV infections resulted in 1.4 million people being affected. InWestern Europe, an estimated 610,000 people were liv-ing with HIV.

Globally, there are 14,000 new HIV infections per day, of which 95% are in developing coun-tries. Approximately 12,000 of these infections are in persons aged 15-49 years of age, of whom almost 50% are women, and 50% are 15-24 years of age. In S. Africa, 1 in 4 women are infected with HIV by the age of 22.

It has been estimated that a 60% efficacious prophylactic treatment, introduced into 73 low-income countries and used by only 20% of women, would avert 2.5 million HIV infections over a period of 3 years in women, men and infants.

In some countries, public health programmes have achieved modest results in reducing HIV rates of infection. Although the use of condoms has slowly increased in countries most severely affected by the HIV epidemic, many vulnerable women are unable to ensure routine use.

The development of new anti-HIV infection and AIDS vaccines and microbicides has been identified as key areas in FP6. This builds on past highquality research programmes on vac-cines and therapeutics supported by the EU, through the programmes FP4 and FP5. However, while significant progress has been achieved in understanding immune response to HIV-1 antigens and in the development of effective antiretroviral therapy, significant challenges to the development of effective preventative strategies still remain. The potential direct impact of this network, therefore, is multifaceted and broad in scope. There is a clear and urgent need to network European microbicide and vaccine research and provide a clear and coordinated strategy for the development of new prevention technology against HIV infection and AIDS.

Such an approach has obvious potential for direct health benefits that will translate into social stability and development. It will offer scientific benefits; by the creation of new knowledge as well as maintaining a strong science base in Europe. It is generally accepted that HIV vaccines and microbicides will have the most significant impact on the growth of this pandemic in both the developing world and within Europe. The potential to derive enormous health benefits, by itself, argues for a strong, integrated approach to the development of HIV-1 prevention strate-gies.

Coordinator:

Partners:

Nº	Principal Scientific Participants	Official Address	Other Information
4	R Shattock / Dr M Cranage J Ma / Dr D Lewis	St. George’s Hospital University of London London UK
5	H Wigzell / Dr BWahren / Dr F Chiodi A-L Spetz	Karolinska Institutet Stockholm SE
6	R Rappuoli / Dr S Barnett G Del Giudice	Novartis Vaccines and Diagnostics Siena IT
7	D Medaglini / Prof G Pozzi	Universita di Siena Siena IT
8	A Tagliabue	ALTA Siena IT
9	G Voss	GlaxoSmith Kline Rixensart BE
10	H Katinger / G Steiglere	Polymun Vienna AT
11	C Kelly / T Lehner L Klavinskis	Kings College London London UK
12	G Scalae	Universita di Napoli Naples IT
13	K Uberla	Ruhr Universitaet Bochum Bochum DE
14	H Holmes / N. Almond R Stebbingse	National Biological Standards Board Potters Bar UK
15	R Weiss	University College London London UK
16	F Gotch / S Patterson	Imperial College of Science, Technology & Medicine London UK
17	V Jespers	Prince Leopold Institute for Tropical Medicine Antwerp BE
18	S McCormack / A Nunn J Bakobaki	Medical Research Council London UK
19	G Scarlatti / G Poli / P Lusso	Centro San Raffaele Milan IT
20	R Le Grand	Commissariat a l’Energie Atomique Paris FR
21	B Verrier C Lacey	Institut National de la Sante et de la Medecine FR University of York York UK
22	Q Sattentau	University of Oxford Oxford UK
23	P La Colla	Università di Cagliari Cagliari IT
24	Christiane Stahl-Hennig	Deutsches Primatenzentrum GmbH Goettingen DE
25	Fenyö	Lunds Universitet Lund SE
26	F Tangy	Institut Pasteur Paris FR
27	H Schuitemaker	Sanquin Amsterdam NL
28	J Alcami / Prof R Najera	Instituto de Salus Carlos III Majadahonda ES
29	G Leroux-Roels	Ghent University Ghent BE
30	D Zipeto	Università di Verona Verona IT
31	S Norley	Robert Koch-Institut Berlin DE
32	E Karamov	Ivanovsky Institute of Virology, Russian Academy of Medical Science Moscow Russia
33	K Nihlmark	Mabtech AB Stockholm SE
34	N Dedes	European AIDS Treatment Group e.V Dusseldorf DE
35	C Moog	Universite Louis Pasteur Strasbourg FR