Schistosoma mansoni gene GP22 encodes the tegumental antigen sm25: (1) antibodies to a predicted B-cell epitope of Sm25 cross-react with other candidate vaccine worm antigens; (2) characterization of a recombinant product containing tandem-repeats of this peptide as a vaccine.
Monospecific antibodies against two putative epitopes of schistosome protein encoded by gene GP22 (182 codons, no introns) were used to probe worm extracts fractionated by lentil-lectin affinity chromatography or by electrophoresis. Anti-peptide-alpha (codons 70-84) exclusively identifies the N-glycanase-sensitive, 25 kDa tegumental glycoprotein Sm25 in the lectin-bound fraction of detergent-solubilized adult worm extract S3. In contrast, antipeptide-delta (codons 151-162) does not react with Sm25 but cross-reacts with other schistosome proteins, including candidate vaccine antigens paramyosin (Sm97) and glutathione-S-transferases (Sm26, Sm28, Sj26). Recombinant protein r4 x 47, constructed to express multiple copies of codon sequence 117-163 (containing delta), reacts with anti-delta and is uniquely recognized by protective Fischer twice-infected (F-2x) rat antiserum. Immunization with r4 x 47 induces antibodies with cross reactivities similar to anti-delta, but which also recognize Sm25. Despite these cross-reactivities with protective antigens, rodents vaccinated with r4 x 47 were not protected against cercarial infection. On the basis of these data, two hypotheses are proposed: (1) antigenic epitopes other than delta are present within the r4 x 47 sequence which induce antibodies reactive with Sm25 and/or (2) peptide-delta assumes alternative antigenic conformations, dependent upon the context of neighbouring sequences, some of which mimic epitopes of proteins encoded by other schistosome genes. These mimotopes are not targets of protective antibodies.
Petzke
M M
MM
Department of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA.
Suri
P K
PK
Bungiro
R
R
Goldberg
M
M
Taylor
S F
SF
Ranji
S
S
Taylor
H
H
McCray
J W
JW
Knopf
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood / Q000276:immunology*; D000947:Antigens, Helminth / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005822:Genetic Vectors; D015801:Helminth Proteins; D037102:Lectins / Q000737:chemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012550:Schistosoma mansoni / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012555:Schistosomiasis mansoni / Q000517:prevention & control*; D020080:Tandem Repeat Sequences / Q000235:genetics; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D018985:Epitopes, B-Lymphocyte; D015801:Helminth Proteins; D037102:Lectins; D008562:Membrane Glycoproteins; D010455:Peptides; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C072491:membrane glycoprotein antigen GP22, Schistosoma; C068960:Sm25 antigen, Schistosoma mansoni