Identification of factors influencing the effectiveness of malaria vaccines: A systematic review

The clinical authorization and deployment of the RTS, S/AS01 and R21/Matrix-M vaccines represent historic milestones in global public health. This systematic review aims to identify, classify, and evaluate the diverse biological, host-specific, environmental, and operational factors that influence the real-world field effectiveness of pre-erythrocytic malaria vaccines. Following PRISMA 2020 guidelines, a systematic literature search was executed across PubMed, Embase, Scopus, and the cochrane library for peer-reviewed studies and programmatic reports tracking malaria vaccine efficacy from January 2015 to April 2026. Data extraction targeted variables driving variations in protection, antibody decay rates, and programmatic dropouts. The synthesis revealed four critical barriers to uniform vaccine effectiveness: Parasite genetics: High genetic polymorphism within the Plasmodium falciparum circumsporozoite protein (Pfcsp) gene enables strain-specific immune evasion, dropping vaccine protection from 50.3% against matching strains down to 33.4% against non-matching field variants. Host Physiological Factors: High baseline maternal anti-CSP antibodies blunt infant B-cell priming in early infancy, while protein-energy malnutrition suppresses clonal expansion and class-switched antibody synthesis, accelerating protective titer decay. Environmental Dynamics: Relentless infectious pressure in ultra-high transmission zones overwhelms vaccine defences, accelerating antibody decay. Malaria vaccine effectiveness is a shifting metric shaped by an intersection of biological and logistical variables. Maximizing population-level survival requires a transition away from rigid, uniform deployment models. Public health strategies must implement agile, region-specific frameworks that combine seasonal vaccination with multivalent antigen formulations, nutritional supplementation, digitized tracking systems, and continuous vector control.