Characterization of Pb51 in Plasmodium berghei as a malaria vaccine candidate targeting both asexual erythrocytic proliferation and transmission

Malaria Journal

Research

Qi Fan¹  Yaru Wang²  Jian Wang²  Yaming Cao²  Li Zheng²  Yiwen He²  Fei Liu²  Liwang Cui³  Enjie Luo⁴  Wenqi Zheng⁵ 

[1] Dalian Institute of Biotechnology, Dalian, Liaoning, China;Department of Immunology, College of Basic Medical Sciences, China Medical University, 110001, Shenyang, Liaoning, China;Department of Immunology, College of Basic Medical Sciences, China Medical University, 110001, Shenyang, Liaoning, China;Department of Entomology, Pennsylvania State University, 16802, University Park, PA, USA;Department of Pathogen Biology, College of Basic Medical Sciences, China Medical University, 110001, Shenyang, Liaoning, China;Laboratory of Surgery, The Affiliated Hospital, Inner Mongolia Medical University, 010050, Hohhot, China;

关键词: Plasmodium berghei;    Pb51;    Vaccine candidate;    Asexual blood stage;    Sexual stage;    Transmission-blocking;   

DOI  :  10.1186/s12936-017-2107-2

 received in 2017-09-04, accepted in 2017-11-02,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundA vaccine that targets multiple developmental stages of malaria parasites would be an effective tool for malaria control and elimination.MethodsA conserved gene in Plasmodium, the Plasmodium berghei gene (PBANKA_020570) encoding a 51 kDa protein (pb51 gene), was identified through search of the PlasmoDB database using a combination of expression and protein localization criteria. A partial domain of the Pb51 protein was expressed in a prokaryotic expression system (rPb51) and used for immunization in mice. The protein expression profile and localization were studied by Western blot and indirect immunofluorescence assay (IFA), respectively. The inhibitory effect of the anti-rPb51 antibodies on parasite proliferation was evaluated in erythrocytes in vivo. The transmission-blocking activity of the immune sera was determined by in vitro ookinete conversion assay and by direct mosquito feeding assay (DFA).ResultsThe rPb51 elicited specific antibodies in mice. Western blot confirmed Pb51 expression in schizonts, gametocytes and ookinetes. IFA showed localization of Pb51 on the outer membranes of schizonts, gametocytes, zygotes, retorts, ookinetes and sporozoites of P. berghei. Mice immunized with the rPb51 protein significantly reduced parasite proliferation and gametocyte conversion in vivo. Moreover, the rPb51 antisera also significantly reduced the in vitro ookinete conversion when added into the ookinete culture medium. In DFA, mice immunized with the rPb51 reduced the prevalence of mosquito infection by 21.3% and oocyst density by 54.8%.ConclusionsIn P. berghei, P51 was expressed in both asexual erythrocytic and sexual stages and localized on the surface of these stages with the exception of the ring stage. The anti-rPb51 antibodies inhibited both P. berghei proliferation in mice and transmission of the parasite to mosquitoes.

【 授权许可】

CC BY   
© The Author(s) 2017