Protective immunity against malaria by a nanoparticle CIS43-based junctional vaccine alone or in combination with R21

Area of Science:

• Immunology
• Vaccinology
• Parasitology

Background:

• Current malaria vaccines like RTS,S/AS01 and R21/Matrix-M target repetitive regions of Plasmodium falciparum circumsporozoite protein (PfCSP).
• The CIS43 monoclonal antibody, targeting the PfCSP junctional epitope, demonstrates high protective efficacy in humans, identifying this region as a critical vaccine target.

Purpose of the Study:

• To develop and evaluate a novel malaria vaccine based on tandem repeats of the PfCSP junctional epitope presented on a self-assembling nanoparticle.
• To compare the efficacy of this CIS43-based junctional vaccine, alone and in combination with the R21 vaccine, in eliciting immune responses and reducing malaria liver burden.

Main Methods:

• Development of a nanoparticle-formatted vaccine displaying tandem repeats of the CIS43 junctional epitope.
• Comparative vaccination studies in preclinical models using the junctional vaccine, R21 vaccine, and a combination thereof.
• Assessment of immune responses through B cell analysis and monoclonal antibody isolation to determine antibody specificities and targeting.

Main Results:

• The best junctional vaccine formulation achieved comparable reduction in malaria liver burden to R21 at a 1μg dose.
• At a lower dose (0.25μg), the junctional vaccine showed a modest reduction in liver burden compared to R21.
• The junctional vaccine induced antibodies against both junctional and major repeat regions of PfCSP, while R21 primarily targeted major repeats.
• Combining the vaccines did not significantly enhance efficacy but showed a modest trend.

Conclusions:

• The nanoparticle-formatted tandem-repeated CIS43-junctional vaccine is a promising strategy for broadening immunity against malaria.
• This approach offers potential as a standalone intervention or in combination with existing vaccines like R21.
• Understanding vaccine-induced antibody specificities is crucial for developing more effective malaria vaccines.