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Questions and Answers
What is the primary endpoint for assessing the efficacy of pre-erythrocytic vaccine candidates?
What is the purpose of administering drug treatment prior to the start of the follow-up period in field trials for blood-stage vaccine candidates?
What is the primary challenge in developing asexual blood-stage vaccines?
What type of whole-parasite blood-stage vaccine has been evaluated in malaria-naive adults?
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What is the name of the vaccine that has shown significant reduction in parasite growth rates in vaccinees following challenge with CHMI?
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What is the name of the antigen used in the 'Combination B' vaccine?
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What is the primary goal of malaria vaccines according to the WHO's preferred product characteristics?
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What is the name of the malaria vaccine that has completed evaluation in phase III trials?
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What is the primary purpose of controlled human malaria infection (CHMI) challenge studies?
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In CHMI studies, how are individuals deliberately exposed to the malaria parasite?
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What is the primary benefit of using CHMI studies before embarking on larger field trials?
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What is the recommended use of RTS,S/AS01 (Mosquirix) according to the WHO?
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Study Notes
WHO's Preferred Product Characteristics for Malaria Vaccines
- Three strategic goals:
- Prevent human blood-stage infection at the individual level
- Reduce malaria morbidity and mortality in individuals at risk in malaria-endemic areas
- Reduce transmission of the parasite and substantially reduce the incidence of human infection in the community
Efficacy Evaluation of Malaria Vaccines
- Clinical evaluation involves three phases:
- Phase I trial: demonstration of safety and immunogenicity
- Controlled human malaria infection (CHMI) challenge studies: assess vaccine efficacy in a controlled environment
- Field trials: assess protection against natural infection in malaria-endemic areas
CHMI Challenge Studies
- Deliberate exposure to malaria parasite through mosquito bite or direct injection of sporozoites or parasitized red blood cells (pRBCs)
- Study endpoint:
- Blood-stage infection detected by microscopy or qPCR for blood-stage vaccine candidates
- Detection of sub-patent blood-stage infection or parasite multiplication rate used for pre-erythrocytic vaccine candidates
Asexual Blood-Stage Vaccines
- Aim: reduce parasite burden and prevent clinical disease
- Achieved by:
- Inducing antibodies that prevent merozoite invasion into new RBCs
- Preventing adhesion of pRBCs to the vasculature in critical organs
- Promoting phagocytosis of pRBCs
- Challenges:
- Difficulties with antigen production
- Redundancy in merozoite invasion ligands, allowing the parasite to evade an immune response
- Limited timeframe for antibodies to neutralize the parasite prior to invasion of RBCs
Types of Blood-Stage Vaccines
- Whole-Parasite Blood-Stage Vaccines:
- Few candidates have progressed beyond pre-clinical evaluation
- Examples:
- Chemically attenuated P.falciparum whole-parasite blood-stage vaccine
- Genetically attenuated P.falciparum whole-parasite blood-stage vaccine (with KAHRP gene deleted)
- Sub-Unit Blood-Stage Vaccines:
- No candidates have progressed into phase III trials
- Examples:
- P.falciparum apical membrane antigen-1 (AMA-1)
- 42kDa C-terminal fragment of merozoite surface protein-1 (MSP-1)
- Reticulocyte-binding protein homolog 5 (Rh5) formulated with AS01B
- 'Combination B': comprising P.falciparum ring-infected erythrocyte surface antigen (RESA) and two merozoite surface proteins (MSP1 and MSP2)
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Description
The WHO's PPC document outlines three strategic goals for malaria vaccine development. Learn about the objectives of preventing blood-stage infection, reducing morbidity and mortality, and reducing transmission.
