MALVAC Scientific Forum Meeting - Progress and Challenges in Development of Whole Organism Malaria Vaccines for Endemic Countries, 3 - 4 June 2009, Dakar, Senegal
At the WHO Initiative for Vaccine Research Scientific Forum Meeting held in Dakar, Senegal on 3-4 June 2009, vaccine researchers, clinical epidemiologists and field trialists together with funders and representatives from regulatory agencies discussed manufacturing, stability, regulatory, ethics, clinical evaluation and logistics considerations related to whole organism malaria vaccines..
The clinical evaluation of malaria vaccines raises numerous complex questions and challenges. In the case of whole organism vaccines several specific additional questions arise for their clinical evaluation, licensure and use post licensure. Whole organism malaria vaccine research and development is progressing rapidly thanks to the major investments over recent years from several funders and the commitment and interest of many leading researchers. Progress has been both in terms of discovery of potential new candidate vaccines and in terms of the starting of the first phase 1 trial of the radiation attenuated sporozoite approach for P. falciparum under the regulatory oversight of the US Food and Drug Administration. Through convening a group of leading scientists, clinical trialists and stakeholders with regulatory representatives from endemic countries, this meeting documented the considerations that will require detailed work in coming years. Should a high level of efficacy be demonstrated in clinical challenge studies, it will become a priority to agree in which populations and age groups questions about dosing, number of doses, route, strain-transcendence and duration of efficacy should be answered, and the appropriate balance between research to improve vaccine presentation and adult and pediatric clinical development in malaria endemic countries. Data presented at the meeting indicated that liquid nitrogen is an absolute requirement for vaccine storage; the challenges that this requirement poses for deployment in sub-Saharan Africa were discussed at the meeting and are summarized in the meeting report. As genetically attenuated sporozoites progress through clinical trials additional questions related to clinical evaluation of live genetically modified parasites will need to be addressed. The several specific considerations related to blood stage whole organism malaria vaccines, which were presented during the meeting, are available below.
WHO provides access to talks given at the meeting with permission from the speakers. The meeting report will be published in an academic journal.
Session I: Background to current and planned whole organism malaria vaccine programmes with discussion of their scientific rationale.
- Development pathways for whole parasite vaccines; Christian Loucq
- Progress Toward Development of a Metabolically Active, Non-Replicating (Live Attenuated) Sporozoite Vaccine; Steven Hoffman
- Overview of background to genetically attenuated sporozoite (GAS) vaccine research and development; Stefan Kappe
- Overview of whole organism blood stage approaches including planned killed whole organism vaccine development; Michael Good
Session 2: Clinical evaluation – discussion of clinical development plans of leading candidates, their scientific rationale and justification
- Clinical development plans with killed blood stage vaccines; Michael Good
- Overview of clinical development plan with leading pre-erythrocytic candidate attenuated malaria vaccines; Thomas Richie / Kirsten Lyke
- Clinical Trials of PfSPZ in Malaria-Experienced Adults and Children in Africa: Pathway to Proof-of-Concept and Licensure; Christopher Plowe
Session 3: Safety considerations for whole organism malaria vaccines – degree of attenuation, use of blood products in production, extraneous agents, examples from other vaccines
- The use of human blood products in manufacturing of vaccines: implications for malaria vaccines; Sanjai Kumar
- Regulatory requirements for lack of extraneous agents for vaccines; examples from whole organism bacterial and/or viral vaccines and implications for malaria. Assessment of degree of attenuation; Roland Dobbelaer
Session 4: Logistics of whole organism malaria vaccines – scale-up, cost, cold-chain
- Optimizing efficiency and scale up of manufacture of the PfSPZ Vaccine to support licensure and launch; Kim Lee Sim
- Stabilization, storage and distribution of attenuated sporozoite vaccines; Eric James
- Liquid Nitrogen Cold-Chain for Malaria Vaccine Distribution in Africa; Manfred Lee
- Logistics challenges associated with the introduction of a vaccine requiring Liquid Nitrogen storage; Modibo Dicko