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

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.

Differential roles of an Anopheline midgut GPI-anchored protein in mediating Plasmodium falciparum and Plasmodium vivax ookinete invasion

“…stephensi and An. gambiae (Armistead, et al, 2014), which at least meets the minimum requirements for the TBV target product profile (Dinglasan et al, 2013; MalERA Consultative Group on Vaccines, 2011). Regardless, further studies are needed to elucidate the mechanism of AgSGU-mediated inhibition of P. falciparum oocyst development, especially given the inability of α-AgSGU PAbs to reduce P. vivax oocyst infection intensity.…”

Differential roles of an Anopheline midgut GPI-anchored protein in mediating Plasmodium falciparum and Plasmodium vivax ookinete invasion

“…stephensi and An. gambiae (Armistead, et al, 2014), which at least meets the minimum requirements for the TBV target product profile (Dinglasan et al, 2013; MalERA Consultative Group on Vaccines, 2011). Regardless, further studies are needed to elucidate the mechanism of AgSGU-mediated inhibition of P. falciparum oocyst development, especially given the inability of α-AgSGU PAbs to reduce P. vivax oocyst infection intensity.…”

Extracellular Vesicles in Malaria: Shedding Light on Pathogenic Depths

“…Among these approaches, the biocompatible polymer named poly(lactic-co-glycolic acid) (PLGA) has been prominently highlighted. 133 Shan Liu and colleagues have focused their research on employing a distinctive ultrasonic atomization technique to produce PLGA microparticles loaded with concentrated malaria plasmid VR1020-MSP119. 132 This technique, known for its ease of formulation and operation, as well as its consistent microparticle synthesis, proves to be commercially feasible for manufacturing biodegradable microparticles consisting of condensed malaria pDNA molecules.…”

“…Controlled gradual release of loaded antigens in biodegradable microparticles, on the other hand, has been shown to produce prolonged functional antibody responses, potentially making the anti-malaria vaccine more powerful. 133 Recently, in a Phase III clinical trial, the RTS,S vaccine showed limited efficacy during a seven-year follow-up among young African children. 135 As a result, there is considerable interest in leveraging the potential of EVs to improve vaccine delivery.…”

“…Previous experiments in malaria vaccine research have predominantly centered around the use of synthetic nanoparticles and microparticles for delivering parasite DNA or proteins. Among these approaches, the biocompatible polymer named poly­(lactic- co -glycolic acid) (PLGA) has been prominently highlighted …”

“…Transmission-inhibiting vaccinations that target the parasite’s sexual stage have been demonstrated to be promising yet inefficient. Controlled gradual release of loaded antigens in biodegradable microparticles, on the other hand, has been shown to produce prolonged functional antibody responses, potentially making the anti-malaria vaccine more powerful …”

Differential roles of an Anopheline midgut GPI-anchored protein in mediating Plasmodium falciparum and Plasmodium vivax ookinete invasion

“…stephensi and An. gambiae (Armistead, et al, 2014), which at least meets the minimum requirements for the TBV target product profile (Dinglasan et al, 2013; MalERA Consultative Group on Vaccines, 2011). Regardless, further studies are needed to elucidate the mechanism of AgSGU-mediated inhibition of P. falciparum oocyst development, especially given the inability of α-AgSGU PAbs to reduce P. vivax oocyst infection intensity.…”

Extracellular Vesicles in Malaria: Shedding Light on Pathogenic Depths

“…Among these approaches, the biocompatible polymer named poly(lactic-co-glycolic acid) (PLGA) has been prominently highlighted. 133 Shan Liu and colleagues have focused their research on employing a distinctive ultrasonic atomization technique to produce PLGA microparticles loaded with concentrated malaria plasmid VR1020-MSP119. 132 This technique, known for its ease of formulation and operation, as well as its consistent microparticle synthesis, proves to be commercially feasible for manufacturing biodegradable microparticles consisting of condensed malaria pDNA molecules.…”

“…Controlled gradual release of loaded antigens in biodegradable microparticles, on the other hand, has been shown to produce prolonged functional antibody responses, potentially making the anti-malaria vaccine more powerful. 133 Recently, in a Phase III clinical trial, the RTS,S vaccine showed limited efficacy during a seven-year follow-up among young African children. 135 As a result, there is considerable interest in leveraging the potential of EVs to improve vaccine delivery.…”

“…Previous experiments in malaria vaccine research have predominantly centered around the use of synthetic nanoparticles and microparticles for delivering parasite DNA or proteins. Among these approaches, the biocompatible polymer named poly­(lactic- co -glycolic acid) (PLGA) has been prominently highlighted …”

“…Transmission-inhibiting vaccinations that target the parasite’s sexual stage have been demonstrated to be promising yet inefficient. Controlled gradual release of loaded antigens in biodegradable microparticles, on the other hand, has been shown to produce prolonged functional antibody responses, potentially making the anti-malaria vaccine more powerful …”

Differential roles of an Anopheline midgut GPI-anchored protein in mediating Plasmodium falciparum and Plasmodium vivax ookinete invasion

“…stephensi and An. gambiae (Armistead, et al, 2014), which at least meets the minimum requirements for the TBV target product profile (Dinglasan et al, 2013; MalERA Consultative Group on Vaccines, 2011). Regardless, further studies are needed to elucidate the mechanism of AgSGU-mediated inhibition of P. falciparum oocyst development, especially given the inability of α-AgSGU PAbs to reduce P. vivax oocyst infection intensity.…”

Extracellular Vesicles in Malaria: Shedding Light on Pathogenic Depths

“…Among these approaches, the biocompatible polymer named poly(lactic-co-glycolic acid) (PLGA) has been prominently highlighted. 133 Shan Liu and colleagues have focused their research on employing a distinctive ultrasonic atomization technique to produce PLGA microparticles loaded with concentrated malaria plasmid VR1020-MSP119. 132 This technique, known for its ease of formulation and operation, as well as its consistent microparticle synthesis, proves to be commercially feasible for manufacturing biodegradable microparticles consisting of condensed malaria pDNA molecules.…”

“…Controlled gradual release of loaded antigens in biodegradable microparticles, on the other hand, has been shown to produce prolonged functional antibody responses, potentially making the anti-malaria vaccine more powerful. 133 Recently, in a Phase III clinical trial, the RTS,S vaccine showed limited efficacy during a seven-year follow-up among young African children. 135 As a result, there is considerable interest in leveraging the potential of EVs to improve vaccine delivery.…”

“…Previous experiments in malaria vaccine research have predominantly centered around the use of synthetic nanoparticles and microparticles for delivering parasite DNA or proteins. Among these approaches, the biocompatible polymer named poly­(lactic- co -glycolic acid) (PLGA) has been prominently highlighted …”

“…Transmission-inhibiting vaccinations that target the parasite’s sexual stage have been demonstrated to be promising yet inefficient. Controlled gradual release of loaded antigens in biodegradable microparticles, on the other hand, has been shown to produce prolonged functional antibody responses, potentially making the anti-malaria vaccine more powerful …”