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Antigens for pre-erythrocytic malaria vaccines: building on success
1Malaria Program, Seattle Biomedical Research Institute, Seattle, WA 98109, USA.
Insights
Attenuated malaria parasite vaccines offer sterile protection. Advances in studying liver-stage parasites and human challenge models are crucial for developing effective malaria vaccines.
Area of Science:
- Malariology
- Vaccinology
- Immunology
Background:
- Attenuated pre-erythrocytic malaria parasites induce sterile protection.
- Subunit vaccines targeting pre-erythrocytic antigens show promise in reducing malaria episodes.
- Research on liver-stage (LS) malaria parasites is limited by technical challenges.
Purpose of the Study:
- To overcome technical hurdles in studying pre-erythrocytic malaria parasites, particularly the liver stage.
- To improve understanding of immune mechanisms conferring protection against malaria in humans.
- To define the transcriptome and proteome of the LS parasite.
Main Methods:
- Utilizing improvements in growing and isolating LS parasites.
- Assessing next-generation pre-erythrocytic antigens through animal immunization studies.
- Employing models of immunity, including attenuated parasite vaccines and naturally acquired immune responses.
- Leveraging a human malaria challenge model for early vaccine candidate testing.
Main Results:
- Progress has been made in defining the transcriptome and proteome of the LS parasite.
- Technical obstacles hindering LS parasite research are being addressed.
- A human malaria challenge model is available for early-stage vaccine evaluation.
Conclusions:
- Further research on early LS parasite stages of Plasmodium falciparum is needed.
- Prioritization of pre-erythrocytic antigens can be informed by animal studies and natural immunity models.
- The human challenge model is vital for advancing candidate malaria vaccines to field trials.
Abstract:
Immunization with attenuated pre-erythrocytic malaria parasites can confer sterile protection against malaria in humans and rodents, and a single pre-erythrocytic antigen incorporated in a subunit vaccine has substantially reduced clinical Plasmodium falciparum malaria episodes in African infants during phase 2 trials. Building upon this success has been hindered by technical obstacles that limit research on pre-erythrocytic parasites, especially the liver stage (LS) parasites, and by an incomplete understanding of the immune mechanisms that confer protection in humans. Recent improvements in growing and isolating LS parasites have allowed progress in defining the transcriptome and proteome of the LS parasite, although more work remains to be done particularly for the early LS parasite of P. falciparum. Next generation pre-erythrocytic antigens can be assessed and prioritized based on immunization studies in animals, and on models of immunity such as attenuated parasite vaccines that confer sterile protection or naturally acquired LS-specific immune responses that correlate with protection in endemic areas. Although mechanisms of protection in humans remain poorly understood, the availability of a human malaria challenge model for early clinical testing of candidate vaccines is a valuable tool to confirm which immunogens should move forward to larger field trials.
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