Podcast
Questions and Answers
What is the primary endpoint for assessing the efficacy of pre-erythrocytic vaccine candidates?
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 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 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?
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?
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?
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?
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?
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?
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?
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?
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?
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.
