Blockade of Plasmodium falciparum erythrocyte invasion: New assessment of anti-Plasmodium falciparum reticulocyte‑binding protein homolog 5 antibodies

Shen,Yan; Wang,Jun; Liu,Xuewu; Liang,Jiao; Huang,Yuxiao; Liu,Zhongxiang; Zhao,Ya; Li,Yinghui

doi:10.3892/etm.2015.2237

Blockade of Plasmodium falciparum erythrocyte invasion: New assessment of anti-Plasmodium falciparum reticulocyte‑binding protein homolog 5 antibodies

Authors:
- Yan Shen
- Jun Wang
- Xuewu Liu
- Jiao Liang
- Yuxiao Huang
- Zhongxiang Liu
- Ya Zhao
- Yinghui Li
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Affiliations: Department of Medical Microbiology and Parasitology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
Published online on: January 29, 2015 https://doi.org/10.3892/etm.2015.2237
Pages: 1357-1362

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Abstract

There is great interest in any new discoveries in malaria vaccine research. Plasmodium falciparum reticulocyte‑binding protein homolog 5 (PfRH5) shows promise in this area and may be used together with other merozoite antigens as a potential vaccine. In the present study, a bioinformatics prediction approach was applied to a PfRH5 B‑cell epitope, and two B‑cell epitope distributions were selected. Antibodies against the two PfRH5 distributions were obtained and the growth activity inhibition was measured. No inhibition of the P. falciparum CY strain was found, but the growth of the P. falciparum 3D7 strain was inhibited by all of the antibodies, in contrast to the results of other studies. It was additionally found that certain quantities of protein led to the inhibition of the parasitic invasion. Equally noteworthy was that the survival time of the group immunized with a portion of PfRH5 was significantly longer than that of the group immunized with the full‑length protein, following infection by P. berghei ANKA. The present study produced conflicting results in in vitro and in vivo experiments, although the accuracy of the evaluation may be lessened due to the use of a murine malaria model. The findings of the present study may indicate that PfRH5 may not be suitable in malaria vaccine research.

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1	Agnandji ST, Lell B, Soulanoudjingar SS, Fernandes JF, Abossolo BP, Conzelmann C, Methogo BG, Doucka Y, Flamen A, Mordmüller B, et al; RTS,S Clinical Trials Partnership. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med. 365:1863–1875. 2011. View Article : Google Scholar : PubMed/NCBI
2	Tolia NH, Enemark EJ, Sim BK and Joshua-Tor L: Structural basis for the EBA-175 erythrocyte invasion pathway of the malaria parasite Plasmodium falciparum. Cell. 122:183–193. 2005. View Article : Google Scholar : PubMed/NCBI
3	Jaśkiewicz E, Graczyk J and Rydzak J: Proteins involved in invasion of human red blood cells by malaria parasites. Postepy Hig Med Dosw (Online). 64:617–626. 2010.(In Polish).
4	Lopaticki S, Maier AG, Thompson J, Wilson DW, Tham WH, Triglia T, Gout A, Speed TP, Beeson JG, Healer J and Cowman AF: Reticulocyte and erythrocyte binding-like proteins function cooperatively in invasion of human erythrocytes by malaria parasites. Infect Immun. 79:1107–1117. 2011. View Article : Google Scholar :
5	Nolan T: Identifying an essential interaction between malaria parasites and erythrocytes unlocks the door to promising vaccine targets. Pathog Glob Health. 106:642012. View Article : Google Scholar : PubMed/NCBI
6	Douglas AD, Williams AR, Illingworth JJ, Kamuyu G, Biswas S, Goodman AL, Wyllie DH, Crosnier C, Miura K, Wright GJ, et al: The blood-stage malaria antigen PfRH5 is susceptible to vaccine-inducible cross-strain neutralizing antibody. Nat Commun. 2:6012011. View Article : Google Scholar : PubMed/NCBI
7	Crosnier C, Bustamante LY, Bartholdson SJ, Bei AK, Theron M, Uchikawa M, Mboup S, Ndir O, Kwiatkowski DP, Duraisingh MT, Rayner JC and Wright GJ: Basigin is a receptor essential for erythrocyte invasion by Plasmodium falciparum. Nature. 480:534–537. 2011.PubMed/NCBI
8	Muramatsu T: Basigin: a multifunctional membrane protein with an emerging role in infections by malaria parasites. Expert Opin Ther Targets. 16:999–1011. 2012. View Article : Google Scholar : PubMed/NCBI
9	Trager W and Jensen JB: Human malaria parasites in continuous culture. 1976. J Parasitol. 91:484–486. 2005. View Article : Google Scholar : PubMed/NCBI
10	Cui L, Rzomp KA, Fan Q, Martin SK and Williams J: Plasmodium falciparum: differential display analysis of gene expression during gametocytogenesis. Exp Parasitol. 99:244–254. 2001. View Article : Google Scholar
11	Jameson BA and Wolf H: The antigenic index: a novel algorithm for predicting antigenic determinants. Comput Appl Biosci. 4:181–186. 1988.PubMed/NCBI
12	Garnier J, Osguthorpe DJ and Robson B: Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins. J Mol Biol. 120:97–120. 1978. View Article : Google Scholar : PubMed/NCBI
13	Creighton TE: Prediction of Protein Structure and the Principles of Protein Conformation. Fasman Gerald D: Plenum; New York: 1989, pp. xivpp. 798illus $95. Science. 247. pp. 1351–1352. 1990
14	Karplus PA and Schulz GE: Prediction of chain flexibility in proteins. Naturwissenschaften. 72:212–213. 1985. View Article : Google Scholar
15	Baum J, Chen L, Healer J, Lopaticki S, Boyle M, Triglia T, Ehlgen F, Ralph SA, Beeson JG and Cowman AF: Reticulocyte-binding protein homologue 5 - an essential adhesin involved in invasion of human erythrocytes by Plasmodium falciparum. Int J Parasitol. 39:371–380. 2009. View Article : Google Scholar
16	Wahlgren M, Berzins K, Perlmann P and Björkman A: Characterization of the humoral immune response in Plasmodium falciparum malaria. I Estimation of antibodies to P falciparum or human erythrocytes by means of microELISA. Clin Exp Immunol. 54:127–134. 1983.PubMed/NCBI
17	Miao J, Li X, Liu Z, Xue C, Bujard H and Cui L: Immune responses in mice induced by prime-boost schemes of the Plasmodium falciparum apical membrane antigen 1 (PfAMA1)-based DNA, protein and recombinant modified vaccinia Ankara vaccines. Vaccine. 24:6187–6198. 2006. View Article : Google Scholar : PubMed/NCBI
18	Jogdand PS, Singh SK, Christiansen M, Dziegiel MH, Singh S and Theisen M: Flow cytometric readout based on Mitotracker Red CMXRos staining of live asexual blood stage malarial parasites reliably assesses antibody dependent cellular inhibition. Malar J. 11:2352012. View Article : Google Scholar : PubMed/NCBI
19	Taylor HM, Grainger M and Holder AA: Variation in the expression of a Plasmodium falciparum protein family implicated in erythrocyte invasion. Infect Immun. 70:5779–5789. 2002. View Article : Google Scholar : PubMed/NCBI
20	Duraisingh MT, Triglia T, Ralph SA, Rayner JC, Barnwell JW, McFadden GI and Cowman AF: Phenotypic variation of Plasmodium falciparum merozoite proteins directs receptor targeting for invasion of human erythrocytes. EMBO J. 22:1047–1057. 2003. View Article : Google Scholar : PubMed/NCBI
21	Nery S, Deans AM, Mosobo M, Marsh K, Rowe JA and Conway DJ: Expression of Plasmodium falciparum genes involved in erythrocyte invasion varies among isolates cultured directly from patients. Mol Biochem Parasitol. 149:208–215. 2006. View Article : Google Scholar : PubMed/NCBI
22	Hayton K, Gaur D, Liu A, Takahashi J, Henschen B, Singh S, Lambert L, Furuya T, Bouttenot R, Doll M, et al: Erythrocyte binding protein PfRH5 polymorphisms determine species-specific pathways of Plasmodium falciparum invasion. Cell Host Microbe. 4:40–51. 2008. View Article : Google Scholar : PubMed/NCBI
23	Rodriguez M, Lustigman S, Montero E, Oksov Y and Lobo CA: PfRH5: a novel reticulocyte-binding family homolog of Plasmodium falciparum that binds to the erythrocyte, and an investigation of its receptor. PloS One. 3:e33002008. View Article : Google Scholar : PubMed/NCBI
24	Rayner JC, Galinski MR, Ingravallo P and Barnwell JW: Two Plasmodium falciparum genes express merozoite proteins that are related to Plasmodium vivax and Plasmodium yoelii adhesive proteins involved in host cell selection and invasion. Proc Natl Acad Sci USA. 97:9648–9653. 2000. View Article : Google Scholar : PubMed/NCBI
25	Triglia T, Duraisingh MT, Good RT and Cowman AF: Reticulocyte-binding protein homologue 1 is required for sialic acid-dependent invasion into human erythrocytes by Plasmodium falciparum. Mol Microbiol. 55:162–174. 2005. View Article : Google Scholar
26	Stubbs J, Simpson KM, Triglia T, Plouffe D, Tonkin CJ, Duraisingh MT, Maier AG, Winzeler EA and Cowman AF: Molecular mechanism for switching of P. falciparum invasion pathways into human erythrocytes. Science. 309:1384–1387. 2005. View Article : Google Scholar : PubMed/NCBI
27	Bustamante LY, Bartholdson SJ, Crosnier C, Campos MG, Wanaguru M, Nguon C, Kwiatkowski DP, Wright GJ and Rayner JC: A full-length recombinant Plasmodium falciparum PfRH5 protein induces inhibitory antibodies that are effective across common PfRH5 genetic variants. Vaccine. 31:373–379. 2013. View Article : Google Scholar :
28	Williams AR, Douglas AD, Miura K, Illingworth JJ, Choudhary P, Murungi LM, Furze JM, Diouf A, Miotto O, Crosnier C, et al: Enhancing blockade of Plasmodium falciparum erythrocyte invasion: assessing combinations of antibodies against PfRH5 and other merozoite antigens. PLoS Pathog. 8:e10029912012. View Article : Google Scholar : PubMed/NCBI
29	Lopez-Perez M, Villasis E, Machado RL, Póvoa MM, Vinetz JM, Blair S, Gamboa D and Lustigman S: Plasmodium falciparum field isolates from South America use an atypical red blood cell invasion pathway associated with invasion ligand polymorphisms. PLoS One. 7:e479132012. View Article : Google Scholar : PubMed/NCBI
30	Villasis E, Lopez-Perez M, Torres K, Gamboa D, Neyra V, Bendezu J, Tricoche N, Lobo C, Vinetz JM and Lustigman S: Anti-Plasmodium falciparum invasion ligand antibodies in a low malaria transmission region, Loreto, Peru. Malar J. 11:3612012. View Article : Google Scholar : PubMed/NCBI