Immunization with Pre-Erythrocytic Antigen CelTOS from Plasmodium falciparum Elicits Cross-Species Protection against Heterologous Challenge with Plasmodium berghei

被引:94
作者
Bergmann-Leitner, Elke S. [1 ]
Mease, Ryan M. [1 ]
De La Vega, Patricia [1 ]
Savranskaya, Tatyana [2 ]
Polhemus, Mark [1 ]
Ockenhouse, Christian [1 ]
Angov, Evelina [1 ]
机构
[1] Walter Reed Army Inst Res, Div Malaria Vaccine Dev, US Mil Malaria Vaccine Program, Silver Spring, MD USA
[2] Walter Reed Army Inst Res, Div Entomol, Silver Spring, MD USA
关键词
CIRCUMSPOROZOITE PROTEIN; MALARIA INFECTION; GENETIC DIVERSITY; IMMUNE-RESPONSES; VACCINE; SPOROZOITES; EFFICACY; PARASITES; CHILDREN; AFFINITY;
D O I
10.1371/journal.pone.0012294
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background: The Plasmodium protein Cell-traversal protein for ookinetes and sporozoites (CelTOS) plays an important role in cell traversal of host cells in both, mosquito and vertebrates, and is required for successful malaria infections. CelTOS is highly conserved among the Plasmodium species, suggesting an important functional role across all species. Therefore, targeting the immune response to this highly conserved protein and thus potentially interfering with its biological function may result in protection against infection even by heterologous species of Plasmodium. Methodology/Principal Findings: To test this hypothesis, we developed a recombinant codon-harmonized P. falciparum CelTOS protein that can be produced to high yields in the E. coli expression system. Inbred Balb/c and outbred CD-1 mice were immunized with various doses of the recombinant protein adjuvanted with Montanide ISA 720 and characterized using in vitro and in vivo analyses. Conclusions/Significance: Immunization with PfCelTOS resulted in potent humoral and cellular immune responses and most importantly induced sterile protection against a heterologous challenge with P. berghei sporozoites in a proportion of both inbred and outbred mice. The biological activity of CelTOS-specific antibodies against the malaria parasite is likely linked to the impairment of sporozoite motility and hepatocyte infectivity. The results underscore the potential of this antigen as a pre-erythrocytic vaccine candidate and demonstrate for the first time a malaria vaccine that is cross-protective between species.
引用
收藏
页数:9
相关论文
共 24 条
[1]   Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children:: randomised controlled trial [J].
Alonso, PL ;
Sacarlal, J ;
Aponte, JJ ;
Leach, A ;
Macete, E ;
Milman, J ;
Mandomando, I ;
Spiessens, B ;
Guinovart, C ;
Espasa, M ;
Bassat, Q ;
Aide, P ;
Ofori-Anyinam, O ;
Navia, MM ;
Corachan, S ;
Ceuppens, M ;
Dubois, MC ;
Demoitié, MA ;
Dubovsky, F ;
Menéndez, C ;
Tornieporth, N ;
Ballou, WR ;
Thompson, R ;
Cohen, J .
LANCET, 2004, 364 (9443) :1411-1420
[2]   Heterologous Protein Expression Is Enhanced by Harmonizing the Codon Usage Frequencies of the Target Gene with those of the Expression Host [J].
Angov, Evelina ;
Hillier, Collette J. ;
Kincaid, Randall L. ;
Lyon, Jeffrey A. .
PLOS ONE, 2008, 3 (05)
[3]   C3d binding to the circumsporozoite protein carboxy-terminus deviates immunity against malaria [J].
Bergmann-Leitner, ES ;
Scheiblhofer, S ;
Duncan, EH ;
Leitner, WW ;
Chen, D ;
Angov, E ;
Khan, F ;
Williams, JL ;
Winter, DB ;
Thalhamer, J ;
Lyon, JA ;
Tsokos, GC .
INTERNATIONAL IMMUNOLOGY, 2005, 17 (03) :245-255
[4]  
COCHRANE AH, 1976, J IMMUNOL, V116, P859
[5]   The clinical-grade 42-kilodalton fragment of merozoite surface protein 1 of Plasmodium falciparum strain FVO expressed in Escherichia coli protects Aotus nancymai against challenge with homologous erythrocytic-stage parasites [J].
Darko, CA ;
Angov, E ;
Collins, WE ;
Bergmann-Leitner, ES ;
Girouard, AS ;
Hitt, SL ;
McBride, JS ;
Diggs, CL ;
Holder, AA ;
Long, CA ;
Barnwell, JW ;
Lyon, JA .
INFECTION AND IMMUNITY, 2005, 73 (01) :287-297
[6]   Identification of Plasmodium falciparum antigens by antigenic analysis of genomic and proteomic data [J].
Doolan, DL ;
Southwood, S ;
Freilich, DA ;
Sidney, J ;
Graber, NL ;
Shatney, L ;
Bebris, L ;
Florens, L ;
Dobano, C ;
Witney, AA ;
Appella, E ;
Hoffman, SL ;
Yates, JR ;
Carucci, DJ ;
Sette, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (17) :9952-9957
[7]   Differential transcriptome profiling identifies Plasmodium genes encoding pre-erythrocytic stage-specific proteins [J].
Kaiser, K ;
Matuschewski, K ;
Camargo, N ;
Ross, J ;
Kappe, SHI .
MOLECULAR MICROBIOLOGY, 2004, 51 (05) :1221-1232
[8]   CelTOS, a novel malarial protein that mediates transmission to mosquito and vertebrate hosts [J].
Kariu, T ;
Ishino, T ;
Yano, K ;
Chinzei, Y ;
Yuda, M .
MOLECULAR MICROBIOLOGY, 2006, 59 (05) :1369-1379
[9]  
KIM YT, 1974, CLIN EXP IMMUNOL, V17, P329
[10]  
Leitner WW, 1997, J IMMUNOL, V159, P6112