Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies.
Cell Rep Med
; 5(7): 101654, 2024 Jul 16.
Article
in En
| MEDLINE
| ID: mdl-39019011
ABSTRACT
Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently in a phase 2b clinical trial as a full-length soluble protein/adjuvant vaccine candidate called RH5.1/Matrix-M. We identify that disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees and that a re-engineered and stabilized immunogen (including just the alpha-helical core of RH5) induces a qualitatively superior growth inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M adjuvant. In parallel, bioconjugation of this immunogen, termed "RH5.2," to hepatitis B surface antigen virus-like particles (VLPs) using the "plug-and-display" SpyTag-SpyCatcher platform technology also enables superior quantitative antibody immunogenicity over soluble protein/adjuvant in vaccinated mice and rats. These studies identify a blood-stage malaria vaccine candidate that may improve upon the current leading soluble protein vaccine candidate RH5.1/Matrix-M. The RH5.2-VLP/Matrix-M vaccine candidate is now under evaluation in phase 1a/b clinical trials.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Plasmodium falciparum
/
Antibodies, Protozoan
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Protozoan Proteins
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Malaria Vaccines
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Vaccines, Virus-Like Particle
Limits:
Animals
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Female
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Humans
Language:
En
Journal:
Cell Rep Med
Year:
2024
Type:
Article