Plasmodium falciparum Cell-traversal protein for ookinetes and sporozoites (PfCelTOS) as a transmission-blocking vaccine candidate: effect of QS-21 and Poly I:C adjuvants on induction of functional antibody with transmission-reducing activity (TRA) in Anopheles stephensi

Background: Transmission-blocking vaccine (TBV) is an essential tool for malaria elimination. PfCelTOS has a crucial role in the traversal of the malaria parasite in both mosquito and mammalian hosts and it is considered as an advanced transmission blocking and infection blocking vaccine candidate. However, subunit PfCelTOS-based vaccine failed to induce strong inhibitory responses with Transmission-reducing activity (TRA) in Anopheles. stephensi (An. stephensi) mosquito. Hence, it is expected that a more potent vaccine formulation will be required to induce high avidity and functional antibody with TRA in An. stephensi mosquito.Objectives: The objective of the present study was to evaluate the capacity of two potent human-compatible adjuvants (QS-21 and Poly I:C) to enhance the immunogenicity of PfCelTOS in BALB/c mice and their ability to enhance TRA of anti-PfCelTOS obtained from different mouse vaccine groups in An. stephensi.Materials and Methods: BALB/c mice were immunized with Escherichia coli-expressed PfCelTOS delivered in QS-21 or Poly I:C adjuvants and head-to-head comparison of the immune responses to PfCelTOS in mouse vaccine groups was performed using conventional and avidity enzyme-linked immunosorbent assay (ELISA). Furthermore, the assessment of TRA of anti-PfCelTOS obtained from different vaccine groups was carried out in female An. stephensi (Mysorensis strain) by using standard membrane feeding assay (SMFA).Results: Administration of PfCelTOS in BALB/c mice in the absence of adjuvant induced relatively low avidity and inhibitory antibodies (47% reduction in oocyst intensity). However, PfCelTOS antigen in combination with QS-21 and/or Poly I:C adjuvants dramatically enhanced anti-PfCelTOS avidity (P < 0.05, one-way ANOVA) and TRA in An. stephensi mosquito (82% and 73.5% reduction in oocyst intensity, respectively) (P < 0.05, Mann-whitney U).Conclusion: This result indicated that PfCelTOS administered in BALB/c mouse in the absence of adjuvant is poorly immunogenic, with relatively low avidity and inhibitory antibodies. However PfCelTOS combination with potent Th1 adjuvants significantly enhanced anti-PfCelTOS avidity and functional activity with TRA in An. stephensi mosquito.

Keywords:

PfCelTOS , Transmission-blocking vaccine , Transmission-reducing activity , QS-21 , Poly I:C