"Acceleration of Blood Stage Vaccine Development Through Use of Clinical Sporozoite and Blood Stage Challenge Models” 18-19 March 2009, Bethesda, MD, USA
A Joint PATH MVI, USAID, EMVI and WHO Initiative for Vaccine Research Scientific Meeting
Pre-erythrocytic malaria vaccine development has benefited enormously from the existence of a clinical sporozoite challenge model. P. falciparum circumsporozoite antigen based vaccines have been iteratively improved using the efficacy readout from this model to the point where a first generation malaria vaccine has been consistently shown to have a degree of proven efficacy in the field. There is now general agreement that sporozoite challenge trials are on the critical path of evaluation for pre-erythrocytic malaria vaccines. Development of an equivalent screening tool for the blood stage vaccine arena may allow a similar process of iterative development to be applied here. There is a bewildering number of potential blood stage regimens when one considers the many possible antigenic components, alleles, formulations and likely multi-component combinations required. This issue coupled with the lack of demonstrated predictive assays and models highlights the major obstacles to rational downselection of candidate regimens for field efficacy trials. Demonstration of retardation of parasite growth rates in challenge trials would provide some confidence that the candidate vaccine blood stage regimen might be clinically efficacious. This in turn would enable a rational use of resources for field trials, where strain transcendence and duration of efficacy could be further explored.
Against this background a meeting was held to explore next steps towards development of a challenge trial screening tool for blood stage vaccines. All centres globally that have undertaken clinical malaria challenge in recent years were represented at the meeting together with vaccine developers, clinical trialists, funders and regulatory representatives. In addition major recent progress with P. vivax clinical challenge was reviewed at the meeting and the performance of clinical challenge trials in sub-Saharan Africa was discussed.
WHO and the co-sponsors provide access to talks given at the meeting with permission from the speakers. The meeting report will be published in an academic journal.
Session 1: Sporozoite challenge trials and evaluation of blood stage vaccines
- 1) Sporozoite challenges and monitoring by PCR in real-time. Adrian Hill
- 2) Sporozoite challenge trials for evaluation of bloodstage candidates. Robert Sauerwein
- 3) Challenge of Volunteers through Needle and Syringe Inoculation of Purified, Cryopreserved Plasmodium falciparum Sporozoites. Stephen Hoffman
Session 2: Blood stage challenge trials and evaluation of blood stage vaccines
- 1) Blood-Stage Challenge Studies. Adrian Hill
- 2) Early Development of a GMP grade whole blood challenge facility. Michael Good
- 3) A GMP Resource of blood stage parasites: why and how? James McCarthy
- 4) Safety and Scientific Issues Specific to Blood Stage Challenge Trials Including Screening of Blood Products for Clinical Use. Sanjai Kumar
Session 3: P. vivax clinical challenge and challenge trials in endemic countries
- 1) Plasmodium vivax sporozoite challenge system in humans: implications for vaccine development. Socrates Herrera
- 2) Plasmodium Vivax Malaria Challenge Model: The USMMVP Effort. Mark Polhemus
- 3) Sanaria's P. vivax Program. Stephen Hoffman
- 4) Challenge trials in Endemic Countries. Kevin Marsh
Session 4: Clinical Safety of Malaria Challenge Model