Preparation and characterization of poly(lactic‐co‐glycolic acid) microparticles containing DNA molecules encoding a malaria vaccine candidate

Abstract

BACKGROUND: A novel ultrasonic atomization approach for the formulation of biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles of a malaria DNA vaccine is presented. A 40 kHz ultrasonic atomization device was used to create the microparticles from a feedstock containing 5 volumes of 0.5% w/v PLGA in acetone and 1 volume of condensed DNA which was fed at a flow rate of 18 ml h −1 . The plasmid DNA vectors encoding a malaria protein were condensed with a cationic polymer before atomization.

Microparticle‐mediated gene delivery for the enhanced expression of a 19‐kDa fragment of merozoite surface protein 1 of Plasmodium falciparum

“…MSP1 is found in all Plasmodium species studied so far, and is the most abundant merozoite surface protein. 6,7 The MSP1 19 remains membrane-bound and contains epidermal growth factor (EGF)-like domains that contain protective epitopes (Figure 1a). [8][9][10] MSP1 19 -specific invasion inhibitory antibodies play a critical role in immunity to Plasmodium blood stage infection.…”

“…The levels of antibody induced were low and no protection was observed. Therefore, high levels of expression of MSP1 19 are required for the development of the current malaria DNA vaccine candidate.…”

“…In our previous studies, we cloned the genes encoding MSP1 19 into a mammalian expression vector VR1020 (Vical, San Diego, CA; Figure 1b) to form a recombinant pDNA construct (VR1020-MSP1 19 ; 5405 bp) and injected the naked recombinant pDNA to test for immunogenicity and protective efficacy in mice. The levels of antibody induced were low and no protection was observed.…”

“…[8][9][10] MSP1 19 -specific invasion inhibitory antibodies play a critical role in immunity to Plasmodium blood stage infection. 11 These were supportive to the development of MSP1 19 -based malaria DNA vaccines.…”

“…4 As the asexual reproductive blood stage of the malaria parasite is the cause of the symptoms in humans, much research has been directed to antigens from that stage. 5 One such vaccine candidate that has been extensively studied is a highly conserved 19 kDa carboxyl-terminal fragment of merozoite surface protein 1 (MSP1 19 ). MSP1 is found in all Plasmodium species studied so far, and is the most abundant merozoite surface protein.…”