Strategies & recent development of transmission-blocking vaccines against Plasmodium falciparum.

Transmission blocking malaria vaccines are aimed to block the development and maturity of sexual stages of parasite within mosquitoes. The vaccine candidate antigens (Pfs25, Pfs48/45, Pfs230) that have shown transmission blocking immunity in model systems are in different stages of development. These antigens are immunogenic with limited genetic diversity. Pfs25 is a leading candidate and currently in phase I clinical trial. Efforts are now focused on the cost-effective production of potent antigens using safe adjuvants and optimization of vaccine delivery system that are capable of inducing strong immune responses. This review addresses the potential usefulness, development strategies, challenges, clinical trials and current status of Plasmodium falciparum sexual stage malaria vaccine candidate antigens for the development of transmission-blocking vaccines.

Cloning,expression and identification of gametocyte specific protein Pfgdv1 of Plasmodium falciparum / 中国血吸虫病防治杂志

Objective To clone a gametocyte specific protein Pfgdv1 of Plasmodium falciparum,express and identify re?combinant Pfgdv1 protein in vitro. Methods PCR was performed to amplify Pfgdv1 from P. falciparum DNA which was got from the patient who was infected with P. falciparum,and the PCR product was inserted into pET28a(+)vector. pET28a?Pfg?dv1 recombinant plasmid was constructed and transformed into E. coli host BL21(DE3+). IPTG was used to induce the recombi?nant Pfgdv1 protein fused with His tag,and the protein was purified by His?NTA affinity chromatography. The recombinant pro?tein was identified by SDS?PAGE and Western blotting. Results The PCR product of Pfgdv1 gene was about 1.65 kb,meeting the expectation of predicted fragment size. The recombinant protein was about 67 kDa,which could be recognized by His?Tag monoclonal antibody. Conclusion The Pfgdv1 gene of P. falciparum is successfully cloned,and the recombinant Pfgdv1 pro?tein is expressed,thereby providing an opportunity for further study on transmission blocking vaccine.

Sequence polymorphisms in Pvs48/45 and Pvs47 gametocyte and gamete surface proteins in Plasmodium vivax isolated in Korea

Nucleotide sequence analyses of the Pvs48/45 and Pvs47 genes were conducted in 46 malaria patients from the Republic of Korea (ROK) (n = 40) and returning travellers from India (n = 3) and Indonesia (n = 3). The domain structures, which were based on cysteine residue position and secondary protein structure, were similar between Plasmodium vivax (Pvs48/45 and Pvs47) and Plasmodium falciparum (Pfs48/45 and Pfs47). In comparison to the Sal-1 reference strain (Pvs48/45, PVX_083235 and Pvs47, PVX_083240), Korean isolates revealed seven polymorphisms (E35K, H211N, K250N, D335Y, A376T, I380T and K418R) in Pvs48/45. These isolates could be divided into five haplotypes with the two major types having frequencies of 47.5% and 20%, respectivelfy. In Pvs47, 10 polymorphisms (F22L, F24L, K27E, D31N, V230I, M233I, E240D, I262T, I273M and A373V) were found and they could be divided into four haplotypes with one major type having a frequency of 75%. The Pvs48/45 isolates from India showed a unique amino acid substitution site (K26R). Compared to the Sal-1 and ROK isolates, the Pvs47 isolates from travellers returning from India and Indonesia had amino acid substitutions (S57T and I262K). The current data may contribute to the development of the malaria transmission-blocking vaccine in future clinical trials.

Malaria transmission blocking immunity and sexual stage vaccines for interrupting malaria transmission in Latin America

Malaria is a vector-borne disease that is considered to be one of the most serious public health problems due to its high global mortality and morbidity rates. Although multiple strategies for controlling malaria have been used, many have had limited impact due to the appearance and rapid dissemination of mosquito resistance to insecticides, parasite resistance to multiple antimalarial drug, and the lack of sustainability. Individuals in endemic areas that have been permanently exposed to the parasite develop specific immune responses capable of diminishing parasite burden and the clinical manifestations of the disease, including blocking of parasite transmission to the mosquito vector. This is referred to as transmission blocking (TB) immunity (TBI) and is mediated by specific antibodies and other factors ingested during the blood meal that inhibit parasite development in the mosquito. These antibodies recognize proteins expressed on either gametocytes or parasite stages that develop in the mosquito midgut and are considered to be potential malaria vaccine candidates. Although these candidates, collectively called TB vaccines (TBV), would not directly stop malaria from infecting individuals, but would stop transmission from infected person to non-infected person. Here, we review the progress that has been achieved in TBI studies and the development of TBV and we highlight their potential usefulness in areas of low endemicity such as Latin America.

Transmission-blocking Vaccine Candidate of Plasmodium vivax Pvs25 Is Highly Conservative among Chinese Isolates / 中国寄生虫学与寄生虫病杂志

Objective To investigate the genetic diversity of Plasmodium vivax transmission_blocking vaccine candidate antigen (TBV) Pvs25, with P.vivax isolates from Hubei and Zhejiang Provinces, and to compare the genetic polymorphism of Pvs25 with that from Bangladesh. MethodsThe parasite DNA used for the genetic polymorphism assay was obtained from dried filter paper blood spots. The genes were PCR amplified and the products were purified and sequenced directly. Results 45 complete new sequences were analyzed. Only 3 nucleotide changes were found that would result in amino acid substitutions in Pvs25 in comparison with the sequence from P.vivax Sal_I strain. The measurement of nucleotide diversity (?) was remarkably similar for the two populations, indicating that DNA sequences and deduced amino acid sequences were highly homologous among the geographically dispersed isolates or isolates from the same geographical region.Conclusion The results suggest that Pvs25 has limited antigenic polymorphism, especially compared with candidate antigens expressed by hepatic and erythrocytic stage, which may support the development and application of Pvs25_based transmission_blocking vaccine in China.