Abstract

Transmission-blocking vaccines (TBVs) targeting Plasmodium gametocytes represent a strategic approach to 
interrupt malaria transmission, complementing existing prevention and treatment measures. This review examined 
the potential of messenger RNA (mRNA) vaccine platforms to deliver gametocyte and mosquito-stage antigens 
capable of eliciting functional antibodies that block parasite development in the mosquito vector. A structured 
literature synthesis and thematic analysis were conducted to integrate current knowledge on gametocyte biology, 
the immunological basis for transmission blocking, and the specific attributes of mRNA technology relevant to such 
targets. Key findings indicated that mRNA platforms offer rapid, scalable production, precise antigen expression, 
and adaptability to conserved gametocyte antigens such as Pfs25, Pfs230, and Pfs48/45. However, challenges 
included ensuring correct antigen folding, achieving thermostability for deployment in resource-limited settings, 
and addressing the ultra-cold chain requirements of current lipid nanoparticle formulations. Preclinical data 
demonstrated promising immunogenicity and functional activity, while early-phase clinical evaluation will require 
innovative regulatory pathways and well-defined endpoints. Successful field implementation will depend on 
overcoming logistical constraints, ensuring affordability through regional manufacturing, fostering community 
acceptance of vaccines with indirect benefits, and integrating TBVs with existing malaria control strategies. 
Prioritizing research on stable formulations, combination approaches, and field-adapted immunogenicity assays will 
be essential for realizing the full potential of mRNA-based TBVs in malaria elimination programs.