DNA vaccines also offer a convenient platform wherein either a single plasmid or a mixture of plasmids each encoding different antigens can be combined to develop a combination vaccine to target multiple stages or multiple species of the malaria parasite [24],[25]

DNA vaccines also offer a convenient platform wherein either a single plasmid or a mixture of plasmids each encoding different antigens can be combined to develop a combination vaccine to target multiple stages or multiple species of the malaria parasite [24],[25]. of parasites after fertilization and is also a lead TBV candidate. DNA plasmids based on codon-optimized sequences of Pfs48/45 and Pfs25 were administered by electroporation, followed by a final recombinant protein boost. Our studies demonstrate that Pfs48/45 encoded by DNA plasmids is capable of inducing potent transmission blocking antibody responses, and such transmission blocking immune potency of Pfs48/45 was not compromised when (S)-3,5-DHPG tested in combination with Pfs25, These findings provide the evidence in favor of further studies on Pfs48/45 and Pfs25, either alone or in combination (S)-3,5-DHPG with other known malaria vaccine candidates for developing effective vaccines capable of interrupting malaria transmission. Keywords: Malaria. Vaccine, Transmission, DNA Vaccine, Combination Vaccine, Target Antigen, Mosquitoes 1. Introduction Vaccines have been crucial in the control and eradication of several infectious diseases and represent one of the most effective public health tools available. Development of vaccines for malaria has focused on antigens Rabbit Polyclonal to SLC39A1 expressed during various stages of the parasite, and malaria transmission blocking vaccines (TBVs) target antigens in sexual and mosquito midgut stage parasites. In these TBV target antigens include Pfs230 and Pfs48/45 expressed on circulating intra-erythrocytic male and female gametocytes and gametes, as well as Pfs25 expressed during mosquito midgut stage development (zygote to ookinete) [1]. Pfs25 has undergone (S)-3,5-DHPG extensive pre-clinical evaluation and a few phase I clinical trials as adjuvant formulated recombinant protein with mixed and varying outcomes [2C5]. Advancements with Pfs48/45 and Pfs230 have lagged, largely because of difficulties in reproducibly expressing recombinant forms of these antigens after initial success [6C8]. Moreover, the paucity of adjuvants for adequate vaccine formulations also hampers overall vaccine development efforts [9]. DNA vaccines, however, provide a single step approach for expressing the antigens in the immunized host cells and simultaneously presenting antigens to the immune system [10]. DNA vaccines encoding Pfs25 and Pvs25 (a ortholog) have revealed highly potent immunogenicity, especially when administered using electroporation in mice and nonhuman primates [11C16]. We have recently also reported on induction of transmission-blocking antibodies in mice by DNA vaccine encoding Pfs48/45 [17]. DNA vaccines were first described in the early 1990s and generated much interest due to their simple design, manufacturability, and the ability to induce both cellular and humoral immune responses [18C23]. DNA vaccines also offer a convenient platform wherein either a single plasmid or a mixture of plasmids each encoding different antigens can be combined to develop a combination vaccine to target multiple stages or multiple species of the malaria parasite [24],[25]. Despite initial promising results, clinical development of DNA plasmid based vaccine (S)-3,5-DHPG development has been hampered, largely due to the relatively low potency seen in nonhuman primates and a few (S)-3,5-DHPG phase I clinical trials, particularly when the DNA is administered by conventional injection [26]. Exact mechanisms of poor immunogenicity of DNA vaccines in are not known and few studies have systematically evaluated several approaches to enhance immune responses, including electroporation based DNA delivery, the use of genetic adjuvants, and sequence optimization for improved protein expression [25,27C29]. Additional studies evaluating these approaches individually, as well as in various combinations, are warranted, especially in nonhuman primate owing to their phylogenetic closeness to humans [30] and their presumed ability to mimic the outcomes expected in humans [26]. The primary objective of the study reported here was to investigate TBV potential of Pfs48/45 encoded by DNA plasmids in rhesus macaques. Additionally, we were able to conduct comparative immunogenicity outcome studies for two TBV antigens (Pfs25 and Pfs48/45, individually and in combination) in nonhuman primates, and assess relative contributions of (i) codon optimization [29], (ii) electroporation [31], (iii) DNA prime C.