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Generating Genetically Modified Plasmodium berghei Sporozoites
Published on: May 5, 2023
Prime-boost vectored malaria vaccines: progress and prospects.
Adrian V S Hill1, Arturo Reyes-Sandoval, Geraldine O'Hara
1The Jenner Institute, University of Oxford, Oxford, UK. adrian.hill@ndm.ox.ac.uk
Human Vaccines
|January 12, 2010
Summary
Viral vectored vaccines show promise for malaria control by inducing T-cell immunity against the liver-stage parasite. Heterologous prime-boost regimens, particularly using simian adenoviruses, demonstrate improved immunogenicity and efficacy in clinical trials.
Area of Science:
- Immunology
- Vaccinology
- Parasitology
Background:
- Inducing protective immunity against malaria via antibodies targeting sporozoites has proven difficult.
- Efforts have shifted towards T-cell immunity against the liver-stage parasite using vectored vaccines.
- Viral vectored vaccines, especially in heterologous prime-boost regimens, show potential for malaria vaccine development.
Purpose of the Study:
- To evaluate the efficacy of viral vectored vaccines in inducing protective immunity against malaria.
- To explore the potential of heterologous prime-boost vaccination strategies for malaria.
- To assess the immunogenicity and efficacy of simian adenoviruses in malaria vaccine development.
Main Methods:
- Assessment of DNA vectored vaccines alone and in combination with viral vectored vaccines.
- Utilization of heterologous prime-boost vaccination regimes.
- Clinical trials (Phase I and IIa) involving simian adenoviruses and modified vaccinia virus Ankara (MVA) in prime-boost strategies.
Main Results:
- DNA vectored vaccines alone were poorly immunogenic and not protective.
- Viral vectored vaccines in heterologous prime-boost regimes achieved high levels of parasite clearance in the liver.
- Simian adenovirus-based prime-boost regimes demonstrated superior immunogenicity and efficacy compared to previous strategies in preclinical and early clinical studies.
- Vectors expressing the TRAP antigen were more immunogenic and protective than those expressing the circumsporozoite protein in human trials.
Conclusions:
- Viral vectored vaccines, particularly simian adenovirus-MVA heterologous prime-boost regimens, represent a significant advancement in malaria vaccine development.
- These approaches have shown repeatable partial efficacy in human trials and hold promise for achieving deployable efficacy in endemic settings.
- Further clinical assessment of these vectors expressing blood-stage antigens is ongoing to induce both T-cell and antibody responses.
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