Immunization with pre-erythrocytic antigen CelTOS from Plasmodium falciparum elicits cross-species protection against heterologous challenge with Plasmodium berghei.
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.


RESULTS
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
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.
Bergmann-Leitner
Elke S
ES
Division of Malaria Vaccine Development, United States Military Malaria Vaccine Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
Mease
Ryan M
RM
De La Vega
Patricia
P
Savranskaya
Tatyana
T
Polhemus
Mark
M
Ockenhouse
Christian
C
Angov
Evelina
E
D000276:Adjuvants, Immunologic; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D004912:Erythrocytes; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D022781:Hepatocytes / Q000469:parasitology; D006801:Humans; D007114:Immunization / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008353:Mannitol / Q000031:analogs & derivatives; D051379:Mice; D009068:Movement; D009829:Oleic Acids; D010962:Plasmodium berghei / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology* / Q000502:physiology; D012995:Solubility; D034101:Sporozoites / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D009829:Oleic Acids; D015847:Interleukin-4; C001681:mannide monooleate; D008353:Mannitol; D007371:Interferon-gamma
Malar J. 2010 May 27;9:145
20507620
Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9952-7
12886016
J Vector Borne Dis. 2008 Mar;45(1):1-20
18399312
Int Immunol. 2005 Mar;17(3):245-55
15710912
Clin Exp Immunol. 1974 Jun;17(2):329-38
4469223
Mol Microbiol. 2004 Mar;51(5):1221-32
14982620
J Infect Dis. 2009 Aug 1;200(3):329-36
19569964
Exp Parasitol. 1993 Sep;77(2):129-35
8375482
Mol Microbiol. 2006 Mar;59(5):1369-79
16468982
J Protozool. 1988 Aug;35(3):389-93
3054075
J Immunol. 1976 Mar;116(3):859-67
815435
Lancet. 2004 Oct 16-22;364(9443):1411-20
15488216
Nature. 1969 May 3;222(5192):488-9
5768632
Infect Immun. 2000 Oct;68(10):5914-9
10992502
J Parasitol. 1984 Oct;70(5):831-3
6150971
PLoS One. 2008 May 14;3(5):e2189
18478103
Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9781-6
10449771
Eur J Immunol. 2001 Mar;31(3):692-8
11241272
Infect Immun. 2005 Jan;73(1):287-97
15618165
J Immunol. 1997 Dec 15;159(12):6112-9
9550412
Biotechniques. 1996 May;20(5):797-800
8723921
Parasite Immunol. 2009 Sep;31(9):560-73
19691559