Induction of protective immunity in mice using a 62-kDa recombinant fragment of a Schistosoma mansoni surface antigen.
Mice exposed to radiation-attenuated cercariae of Schistosoma mansoni are highly resistant to challenge infection, and sera from these mice can confer partial resistance when transferred to naive recipients. These sera recognize Ag present in schistosomular and adult worms, among them an Ag of 200 kDa. A cDNA encoding a 62-kDa portion of this Ag was cloned; the deduced amino acid sequence of this cDNA clone shares homology with myosins of other species. To assess the immunoprophylactic potential, we carried out vaccination trials in mice using the recombinant polypeptide expressed as a fusion protein with beta-galactosidase presented in the form of proteosome complexes with the outer membrane protein of meningococcus. The level of protection achieved was 32%, and this level could be increased to 75% by removal of those amino acids included in the fusion protein that were derived from the vector to yield a polypeptide, designated rIrV-5. A similar level of protection was achieved when mice were immunized with the same dose of rIrV-5 in the form of protein complexes but without outer membrane protein, suggesting that protection did not require the use of adjuvant. However, at least three immunizations were necessary to achieve protection. Using mAb and sera from mice vaccinated with rIrV-5, we demonstrated that the native protein recognized by antibodies against rIrV-5 is a 200-kDa protein that is expressed on the surface of newly transformed schistosomula. The protection achieved with rIrV-5 in mice encourages additional studies of its potential as a vaccine candidate for the prevention of schistosomiasis.
Soisson
L M
LM
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Masterson
C P
CP
Tom
T D
TD
McNally
M T
MT
Lowell
G H
GH
Strand
M
M
D000595:Amino Acid Sequence; D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology; D000947:Antigens, Helminth / Q000737:chemistry* / Q000276:immunology; D000954:Antigens, Surface / Q000737:chemistry* / Q000276:immunology; D001483:Base Sequence; D003001:Cloning, Molecular; D015801:Helminth Proteins / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D009218:Myosins / Q000737:chemistry; D010455:Peptides / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology*; D016415:Sequence Alignment; D014614:Vaccines, Synthetic / Q000276:immunology*
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D000954:Antigens, Surface; D015801:Helminth Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D009218:Myosins