Multi-antigen transmission-blocking malaria vaccine elicits Th1-biased antibody responses and SMFA-confirmed oocyst reduction in Anopheles stephensi.

BACKGROUND

The persistent global burden of malaria highlights the urgent need for innovative vaccine strategies with the ability to block transmission of Plasmodium falciparum. This study presents a novel multi-component Transmission Blocking Vaccine (TBV) formulation, which integrates the antigens APN-1, CelTOS, and cd-HAP with the adjuvants CPG, MPL, and QS-21, with the aim of inducing broad immune responses targeting multiple parasite and mosquito stages.

METHODS

Recombinant antigens were expressed in E. coli and formulated as single-antigen or triple-antigen vaccine formulations, with or without adjuvants. BALB/c mice were immunized, and sera were collected for antibody and cytokine profiling. Functional activity was measured by standard membrane feeding assay (SMFA) using P. falciparum NF54 gametocytes and Anopheles stephensi.

RESULTS

The multi-component vaccine elicited robust high avidity IgG antibody responses against all three antigens without evidence of antigenic interference. Notably, it induced robust Th1-type cellular responses, characterized by increased IFN-γ and TNF production, which are critical for effective anti-parasitic immunity. Efficacy was further demonstrated through the Standard Membrane Feeding Assay (SMFA), which revealed that the induced antibodies substantially reduced oocyst load, a promising pathway for advancing malaria vaccine development.

CONCLUSION

These findings underscore the potential of multi-component TBV vaccines to induce efficient transmission blocking immune responses without compromising individual antigen performance. The multicomponent TBV approach offers a practical framework for simultaneously targeting multiple stages of malaria transmission and supports further development of combination transmission-blocking vaccine strategies.