Single-dose microparticle delivery of a malaria transmission-blocking vaccine elicits a long-lasting functional antibody response.

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.

Expression, immunogenicity, histopathology, and potency of a mosquito-based malaria transmission-blocking recombinant vaccine.

Vaccines have been at the forefront of global research efforts to combat malaria, yet despite several vaccine candidates, this goal has yet to be realized. A potentially effective approach to disrupting the spread of malaria is the use of transmission-blocking vaccines (TBV), which prevent the development of malarial parasites within their mosquito vector, thereby abrogating the cascade of secondary infections in humans. Since malaria is transmitted to human hosts by the bite of an obligate insect vector, mosquito species in the genus Anopheles, targeting mosquito midgut antigens that serve as ligands for Plasmodium parasites represents a promising approach to breaking the transmission cycle. The midgut-specific anopheline alanyl aminopeptidase N (AnAPN1) is highly conserved across Anopheles vectors and is a putative ligand for Plasmodium ookinete invasion. We have developed a scalable, high-yield Escherichia coli expression and purification platform for the recombinant AnAPN1 TBV antigen and report on its marked vaccine potency and immunogenicity, its capacity for eliciting transmission-blocking antibodies, and its apparent lack of immunization-associated histopathologies in a small-animal model.

Interspecific larval competition between Aedes albopictus and Aedes japonicus (Diptera: Culicidae) in northern Virginia.

Aedes albopictus (Skuse) and Aedes japonicus (Theobald) are two of the most recent and widespread invasive mosquito species to have become established in the United States. The two species co-occur in water-filled artificial containers, where crowding and limiting resources are likely to promote inter- or intraspecific larval competition. The performance of northern Virginia populations of Ae. japonicus and Ae. albopictus competing as larvae under field conditions was evaluated. Per capita rates of population increase for each species were estimated, and the effects of species composition and larval density were determined. In water-containing cups provided with oak leaves, Ae. albopictus larvae exhibited a competitive advantage over Ae. japonicus as a consequence of higher survivorship, shorter developmental time, and a significantly higher estimated population growth rate under conditions of interspecific competition. Intraspecific competition constrained population performance of Ae. albopictus significantly more than competition with Ae. japonicus. In the context of the Lotka-Volterra model of competition, these findings suggest competitive exclusion of Ae. japonicus in those habitats where this species co-occurs with Ae. albopictus.