Workshop on molecular biological and immunological aspects of the malaria vaccine, Centre International de Recherches Medicales de FrancevilleFranceville, Gabon, 10-14 April, 2000

David Arnot, University of Edinburgh

Overview
The Workshop was successfully held as advertised. The first point to note is that it was a significant logistics exercise to bring 30 African students from 17 African countries and African, European and American facilitators from the three continents to a fairly remote central African research institution efficiently and safely. Ntoumi and her CIRMF colleagues deserve congratulations on managing this huge task with aplomb. The second point to note was that there was a real meeting of minds and a terrific learning experience for all parties. AMVTN pulled off a significant achievement in the development of African malaria research and this meeting will be part of its history.

The Seminars
After an opening ceremony and welcome from the Director of CIRMF, the Workshop opened with a first session "Immunity to infection and immunity to malaria: Mechanisms, Principles and Common Themes". Each of the first three review talks was intended to provide an overview of current research on the immunology and immuno-epidemiology of malaria. David Arnot (Edinburgh University & AMVTN CC) spoke on "Immunity to malaria and malaria epidemiology" and Thor Theander (Copenhagen University and AMVTN CC) followed on with a review of "Antibody responses to malaria infections in the populations of endemic areas and their role in protection and pathology'. Cellular immune mechanisms were then reviewed by Lars Hviid (Copenhagen University and AMVTN Webmaster) in a presentation entitled "Cellular immune responses to malaria infection in humans and their role in protection and pathology".

After lunch, the seminar re-started with a review of what is known about 'Host cell invasion by malaria parasites' (Daniel Camus, University of Lille), followed by a report on the current status of research on 'Merozoite proteins: function and immunogenicity' (Tony Holder, National Institute for Medical Research, London). An intense first day was then brought to a close by two speakers who were invited to participate in order to bring a fresh perspective on malaria immunology and vaccine research from the view point of 'pure' immunology. David Gray (Edinburgh University) reviewed 'Immunological Memory' and Polly Matzinger (National Institutes of Health, Bethesda Maryland) presented her re-interpretation of the organisational basis of the immune system in an exposition entitled 'Immunity to Infection- Non-Self or Danger?' Both of these memorable talks were particularly well received by the audience and stimulated a great deal of discussion. For both of these speakers it was their first 'African' lecture and it was felt that this aspect of the seminar had been a unique experience for the participants.

The seminar's theme for the second day was 'Malaria in Africa. Pathogenesis and Immunity' and was got going by a review of research on 'Severe malaria disease syndromes' (Robert Sauerwein, Nijmegen University & AMVTN CC). The theme of malaria parasite genetic diversity was then opened with a presentation by Francine Ntoumi (CIRMF, Gabon & AMVTN CC) on 'Molecular analysis of P. falciparum isolates from different sites in Gabon'. This theme was continued in two further talks that morning, on 'Endemicity and clone multiplicity effects on malaria virulence in Ghana and Sudan' (David Arnot) and 'Epidemiology, allelic diversity and turnover rates of Plasmodium falciparum infections in Tanzanian children' (Stephen Magesa, National Institute for Medial Research, Amani Research Centre, Tanzania).

The subject of possible differences in malaria epidemiology induced by human genetic factors and by transmission intensity differences were covered in the final two talks that morning 'Human genetic factors and specific immunity in relation to mild malaria in Gabon' (Florence Migot-Nabias, CIRMF, Gabon) and 'Immuno-epidemiology of malaria in populations exposed to different levels of malaria transmission' (Thor Theander).

The afternoon of the second intensive day of seminarising was oriented mainly towards vector and transmission related malaria research. It was opened with presentations by Vincent Robert, (IRD, Dakar, Senegal) on 'Malaria morbidity and vector control' and Djibril Sangre (Department d'Epidemiologie des affections parasitaires, University of Mali, Bamako) on 'Natural Transmission of P. falciparum genotypes by Anopheles gambiae complex members'. The flow of entomologically oriented discussion was interrupted by a presentation on the 'Analysis of genetic factors controlling malaria infections in humans' by Yves Traore, Centre Muraz, Ouagadougou,, Burkina Faso. A hard day's seminarising was brought to a satifying close as 'Transmission blocking immune responses to malaria infection' were reviewed by Robert Sauerwein.

The theme of the third day was an attempt to get down to the business of 'The Development of Malaria Vaccines' and was initiated by our immunological gurus. Polly Matzinger spoke on 'Immunological Theories and improved vaccination' and David Gray tackled the thorny question of 'How does vaccination induce memory? This was followed up by a progress report on the extensive vaccine development programme currently under way in the U.S. Navy Laboratory under the direction of Steve Hoffman. This was given by one of the active researchers in this group, Martha Sedegah (Naval Medical Research Centre, Maryland, USA) and entitled 'DNA Vaccines against Malaria'. The morning ended with a summation of research progress on MSP-1 vaccines entitled 'Development of Merozoite surface protein-1 based vaccines' (Tony Holder).

The vaccine development theme was continued after lunch by Pierre Druihle (Institute Pasteur, Paris) on 'Protection against malaria by pre-erythrocytic stage antigens'. This was then followed by two reports 'from the field' on vaccine trials. Mike Wilson (Noguchi Institute, University of Ghana, Accra) reported on 'Malaria, health demography and malaria vaccine trial sites: the Navrongo Project in Northern Ghana'. The last talk before an early evening excursion trip on the river through the Gabonese forest was from Zainab Njie (MRC Gambia Labs) on 'The RTS,S/SBAS2 candidate vaccine trial against malaria in the Gambia'.

The 4th day of the Seminar was intended to incorporate time in the afternoon for some sightseeing in the Gabon or in the primatology facilities at CIRMF or indeed just to rest after some fairly concentrated malaria vaccinology. The major theme of the morning only session was Malaria in Pregnancy. The session was introduced by Phillipe Deloron (CIRMF, Gabon) reviewing 'Clinical, parasitological and immunological features of malaria in pregnant women and their offspring'. Two talks on data from ongoing African studies were then presented ' The prevalence of P. falciparum, P. malariae and P. ovale infections in pregnant Cameroonian women' (Rosine Djokam, Universite de Yaunde, Cameroon) and 'Parasite populations in the venous and placental blood of pregnant women at delivery' (Brenda Okech Apio. Med. Biotech Laboratories, Kampala, Uganda).

After coffee, the torch was taken up by Lars Hviid who reported recent advances in our understanding of 'Cytoadherence of P. falciparum infected red blood cells to chondroitin sulphate (CSA) and immune responses to CSA binding parasites'. A very good session in this fast moving area of malaria research was then wound up by Polly Matzinger who presented 'Some thoughts on the immunology of malaria in pregnancy'. The session was then brought to a close with an invited presentation from Professor Lebibi (University of Sciences and Technology of Masuku, Franceville, Gabon) on 'Novel chemo-therapeutics against drug resistant malaria'.

The main subject of the 5th and last day of the Workshop was 'Antigenic variation, antigenic polymorphism and vaccine research'. The introductory review was given by David Arnot on 'Antigenic variation and var genes encoding PfEMP-1 adhesion receptors'. Results for a longitudinal survey in Sudan were presented in a talk on 'Antibody mediated agglutination of P. falciparum infected erythrocytes: the serology of antigenic variation' (Haider Giha, Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan). Another serologically oriented analysis was presented by Daniel Dodoo (Noguchi Institute, University of Ghana) on 'Identification of potential vaccine candidate antigens by correlating observed antibody responses to protection against clinical malaria'.

After a last coffee break the two final presentations were given 'Experimental malaria challenge in humans and malaria vaccine trials' by Robert Sauerwein and Pierre Druilhe reviewed work from his laboratory on 'Mechanisms of host defence against blood stage infections and identification of key target antigens.' After a last effort to fill in course evaluation questionaires.

The workshops formal sessions closed and it remained only to have the conference banquet at the Leconi Palace Hotel, Franceville where an excellent time was had by all.

The learning experience of the participants: 
As can be seen from the above, 5 intense days of seminars took place. These were deliberately mixed such that the superb chalk and blackboard immunological ideas seminars of Dr. Grey and Dr. Matzinger were mixed with ' professional malaria' talks and presentations from the participants themselves. This format worked well and it was remarkable how smoothly things did flow between the presentations of speakers such as Dr. Matzinger (increasing mentioned as a possible Nobel prize winner) and presentations from graduate student participants. This was a great experience for the younger scientists on the course and they rose to the challenge remarkably. The pre-circulation of a Course Book of relevant papers and the distribution of key reprints by most speakers helped a lot here.

Participant questionnaires. 
These are overwhelmingly positive and are available for inspection. Unfortunately the very detailed questionnaire was lost in e-mail transit but a last minute one was produced.

What were the anticipated problems and how were they overcome?

1. Travel to Gabon and Franceville. - After preparation, this went remarkably smoothly. We had to bias student selection to West and Central Africa for reasons of budget and this was wise because all the East Africans had travel problems that were costly to resolve.
2. Accommodation. - With the transit stop in Libreville, this increased costs. We managed, but the costs of accessing sites must be considered in future decisions.
3. Teaching Methods. - The discursive seminar techniques worked with this size of group (around 45). Obviously different levels of knowledge existed but the presentations were of high teaching quality. Different teaching methods such as more debates and more group work might be experimented with in future.
4. Language- The French-English problem exists but was coped with. Translation (again an additional cost) was available and around 20% of presentations were in French.
5. Social interactions. - There was good mixing between the big group and a couple of nice trips and densely packed buses allowed everyone to get to know each other. Health and Safety of participants.- Thankfully no problems were encountered and no one got malaria.
6. Unreliable airlines were anticipated. Problems arising (as usual) involved having to spend money on things we would prefer not to have to spend money on such as prolonged accommodation awaiting cancelled and re-routed return flights.
7. Overall budget. We had a budget of around $65,000 dollars to run this workshop and we came in at the end, within budget-a small miracle. A vote of thanks to our sponsors, the European Commission.

Conclusion. 
This was hard work but it was worth it. AMVTN conceived and ran a major international Workshop on modern malaria vaccinology in Gabon. It was thus able to progress towards one of its goals, to educate and train African scientists, particularly the younger generation of malaria researchers, in the immunology and molecular biology underlying the latest developments in malaria vaccine research.

It is worth noting that the Gabonese government and media were very supportive of the Meeting and it was reported on daily by the press and there was an evening report from the conference on Gabonese television each day. Particular thanks to Dr. Polly Matzinger for her appearances in frequent press conferences at which her excellent French was put to good use.