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.
Hirunpetcharat
C
C
Malaria and Arbovirus Unit, The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane 4029, Australia.
Stanisic
D
D
Liu
X Q
XQ
Vadolas
J
J
Strugnell
R A
RA
Lee
R
R
Miller
L H
LH
Kaslow
D C
DC
Good
M F
MF
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