Intranasal immunization with yeast-expressed 19 kD carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (yMSP119) induces protective immunity to blood stage malaria infection in mice.
Variable protection against malaria blood-stage infection has been demonstrated in mice following parenteral immunization with the highly conserved 19 kD carboxylterminal fragment of the merozoite surface protein-1 (MSP119) using CFA/IFA and other adjuvants. Here we show that intranasal immunization of BALB/C mice with yeast expressed Plasmodium yoelii MSP119 plus a mixture of native and recombinant cholera toxin B subunit, could induce serum MSP119-specific antibodies at titres ranging from 20 000 to 2 560 000. The Ig subclass responses were predominantly G1 and G2b. Intranasal immunization led to protection following challenge (peak parasitaemia < 1%) in mice with the highest MSP119-specific titre (>/= 640 000). In two of the three protected mice, a peak parasitaemia of 0.1%-1% was followed by a boost of the antibody response whereas one of the three protected mice did not boost its antibody response after a peak parasitaemia of 0.02%. In unprotected mice, antibody levels rose, then fell, following the detection of parasites in the peripheral blood. CD4+ T cell-depletion abrogated the ability of the mice to boost their antibody response following challenge. These data demonstrate the potential for intranasal immunization with MSP119 to protect against malaria.
Malaria and Arbovirus Unit, The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane 4029, Australia.
C
C
Hirunpetcharat
D
D
Stanisic
X Q
XQ
Liu
J
J
Vadolas
R A
RA
Strugnell
R
R
Lee
L H
LH
Miller
D C
DC
Kaslow
M F
MF
Good
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002772:Cholera Toxin / Q000008:administration & dosage; D007114:Immunization; D008212:Lymphocyte Depletion; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D020066:Merozoite Surface Protein 1 / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*; D010967:Plasmodium yoelii / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments; D011994:Recombinant Proteins; D002772:Cholera Toxin