Monoclonal antibody against the Plasmodium falciparum chitinase, PfCHT1, recognizes a malaria transmission-blocking epitope in Plasmodium gallinaceum ookinetes unrelated to the chitinase PgCHT1

被引:30
作者
Langer, RC
Li, FW
Popov, V
Kurosky, A
Vinetz, JM
机构
[1] Univ Texas, Med Branch, WHO Collaborating Ctr Trop Dis, Galveston, TX 77555 USA
[2] Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77555 USA
[3] Univ Texas, Med Branch, Dept Human Biol Chem & Genet, Galveston, TX 77555 USA
关键词
D O I
10.1128/IAI.70.3.1581-1590.2002
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To initiate invasion of the mosquito midgut, Plasmodium ookinetes secrete chitinases that are necessary to cross the chitin-containing peritrophic matrix en route to invading the epithelial cell surface. To investigate chitinases as potential immunological targets of blocking malaria parasite transmission to mosquitoes, a monoclonal antibody (MAb) was identified that neutralized the enzymatic activity of the sole chitinase of Plasmodium falciparum, PfCHT1, identified to date. This MAb, designated 1C3, previously shown to react with an apical structure of P. falciparum ookinetes, also reacts with a discrete apical structure of A gallinaceum ookinetes. In membrane feeding assays, MAb 1C3 markedly inhibited P. gallinaceum oocyst development in mosquito midguts. MAb 1C3 affinity isolated an similar to210-kDa antigen which, under reducing conditions, became a 35-kDa antigen. This isolated 35-kDa protein cross-reacted with an antiserum raised against a synthetic peptide derived from the A gallinaceum chitinase active site, PgCHT1, even though MAb 1C3 did not recognize native or recombinant PgCHT1 on Western blot. Therefore, this affinity-purified 35-kDa antigen appears similar to a previously identified protein, PgCHT2, a putative second chitinase of P. gallinaceum. Epitope mapping indicated MAb 1C3 recognized a region of PfCHT1 that diverges from a homologous amino acid sequence conserved within sequenced chitinases of A berghei, P. yoelii, and A gallinaceum (PgCHT1). A synthetic peptide derived from the mapped 10 epitope may be useful as a component of a subunit transmission-blocking vaccine.
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收藏
页码:1581 / 1590
页数:10
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