Single-Dose Microparticle Delivery of a Malaria Transmission- Blocking Vaccine Elicits a Long-Lasting Functional Antibody Response

R.R.      Dinglasan; J.S.      Armistead; J.F.      Nyland; X.      Jiang; H.Q.      Mao

Abstract

Malaria sexual stage and mosquito transmission-blocking vaccines (SSM-TBV) have recently gained prominence as a necessary tool for malaria eradication. SSM-TBVs are unique in that, with the exception of parasite gametocyte antigens, they primarily target parasite or mosquito midgut surface antigens expressed only inside the mosquito. As such, the primary perceived limitation of SSM-TBVs is that the absence of natural boosting following immunization will limit its efficacy, since the antigens are never presented to the human immune system. An ideal, safe SSM-TBV formulation must overcome this limitation. We provide a focused evaluation of relevant nano-/microparticle technologies that can be applied toward the development of leading SSM-TBV candidates, and data from a proof-of-concept study demonstrating that a single inoculation and controlled release of antigen in mice, can elicit long-lasting protective antibody titers. We conclude by identifying the remaining critical gaps in knowledge and opportunities for moving SSM-TBVs to the field.

Keywords: Antigen, controlled release, immunity, malaria, midgut, mosquito, nanotechnology, natural boosting, sexual stages, transmission-blocking vaccine