Induction of broadly neutralizing antibodies against measles virus mutants using a polyepitope vaccine strategy.
Chimeric molecules expressing multiple copies of the loop-forming hemagglutinin noose epitope (designated as "L"; aa386-400), a protective B cell epitope of the measles virus were generated by recombinant technology. The recombinant polyepitope [L4T4]2 combining two sets of four repeats of the L epitope and with two sets of four repeats of the human promiscuous T cell epitope of tetanus toxoid ("T", tt830-844) was produced in transgenic carrot plants. After intraperitoneal immunization of mice with plant membrane extract, sera neutralized all wild-type viruses. In a modified plaque reduction neutralization assay based on CD150-transfected Vero cells anti-[L4T4]2 sera neutralized all field isolates, irrespective of mutations in the L epitope. Even viruses with a mutation in the contact residues of a neutralizing L-specific monoclonal antibody or two mutations in other positions of the epitope were equally sensitive to neutralization. These results suggest that the multiple copies of the L epitope fold into different conformations that induce a repertoire of B cells diverse enough to overcome the genetic diversity of field viruses.
Bouche
Fabienne B
FB
Institute of Immunology and WHO Collaborative Center for Measles, Laboratoire National de Santé, 20 A rue Auguste Lumière, L-1950 Luxembourg, Luxembourg.
Steinmetz
André
A
Yanagi
Yusuke
Y
Muller
Claude P
CP
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000956:Antigens, Viral / Q000235:genetics; D002522:Chlorocebus aethiops; D000939:Epitopes / Q000235:genetics; D006801:Humans; D008458:Measles Vaccine / Q000235:genetics* / Q000276:immunology*; D008459:Measles virus / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D030821:Plants, Genetically Modified; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D008458:Measles Vaccine; D014614:Vaccines, Synthetic; D014764:Viral Proteins