Belmonte, M., et al. Immunogenicity of HLA-restricted peptide vaccine candidates delivered by self-assembling protein nanoparticle (SAPN) technology. Vaccine, 2025 Oct 12, 66:127832.

Belmonte, M., et al. Immunogenicity of HLA-restricted peptide vaccine candidates delivered by self-assembling protein nanoparticle (SAPN) technology. Vaccine, 2025 Oct 12, 66:127832. PMID: 41082812

• Effective long-term vaccines are urgently needed to overcome the parasite’s complexity and reduce the global malaria burden. This study aims to develop and evaluate HLA-restricted peptide vaccines using self-assembling protein nanoparticles (SAPNs) to elicit robust cellular and humoral immunity against malaria. 
• The designed SAPN vaccines, containing conserved and promiscuous HLA-restricted epitopes from P. falciparum antigens, successfully elicited strong cellular immune responses, particularly IFN-γ producing T cells, and significantly increased antibody titers against sporozoites in transgenic mice. Additionally, the study showed that these epitope-based vaccines can induce multifunctional immune responses, supporting their promise as vaccine candidates for malaria. 
• The paper highlights the crucial role of saponins, such as QS-21, as key components of the ALFQ adjuvant used in SAPN vaccine formulations to enhance immunogenicity. The role of QS-21 is to stimulate and diversify the immune response, promoting stronger antibody and T-cell responses against the vaccine antigens. By incorporating QS-21 into the adjuvant, the authors aimed to improve the efficacy of the vaccine formulations, leveraging saponins’ known ability to activate immune cell pathways and enhance vaccine-induced protection. 
• The findings support the feasibility of epitope-based adjuvanted SAPN vaccines as a promising strategy for malaria prevention, leveraging bioinformatics-driven epitope prediction and multiepitope nanoparticle platforms to develop effective, immunogenic, and broadly applicable vaccines

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