title: A molecularly cloned Schwarz strain of measles virus vaccine induces strong immune responses in macaques and transgenic mice.
abstract: Live attenuated RNA viruses make highly efficient vaccines. Among them, measles virus (MV) vaccine has been given to a very large number of children and has been shown to be highly efficacious and safe. Therefore, this vaccine might be a very promising vector to immunize children against both measles and other infectious agents, such as human immunodeficiency virus. A vector was previously derived from the Edmonston B strain of MV, a vaccine strain abandoned 25 years ago. Sequence analysis revealed that the genome of this vector diverges from Edmonston B by 10 amino acid substitutions not related to any Edmonston subgroup. Here we describe an infectious cDNA for the Schwarz/Moraten strain, a widely used MV vaccine. This cDNA was constructed from a batch of commercial vaccine. The extremities of the cDNA were engineered in order to maximize virus yield during rescue. A previously described helper cell-based rescue system was adapted by cocultivating transfected cells on primary chicken embryo fibroblasts, the cells used to produce the Schwarz/Moraten vaccine. After two passages the sequence of the rescued virus was identical to that of the cDNA and of the published Schwarz/Moraten sequence. Two additional transcription units were introduced in the cDNA for cloning foreign genetic material. The immunogenicity of rescued virus was studied in macaques and in mice transgenic for the CD46 MV receptor. Antibody titers and T-cell responses (ELISpot) in animals inoculated with low doses of rescued virus were identical to those obtained with commercial Schwarz MV vaccine. In contrast, the immunogenicity of the previously described Edmonston B strain-derived MV clone was much lower. This new molecular clone will allow for the production of MV vaccine without having to rely on seed stocks. The additional transcription units allow expressing heterologous antigens, thereby providing polyvalent vaccines based on an approved, safe, and efficient MV vaccine strain that is used worldwide.
authors.affiliation: Unité des Virus Lents, CNRS URA 1930, Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Combredet
authors.forename: Valérie
authors.initials: V
authors.lastname: Labrousse
authors.forename: Lucile
authors.initials: L
authors.lastname: Mollet
authors.forename: Clarisse
authors.initials: C
authors.lastname: Lorin
authors.forename: Frédéric
authors.initials: F
authors.lastname: Delebecque
authors.forename: Bruno
authors.initials: B
authors.lastname: Hurtrel
authors.forename: Harold
authors.initials: H
authors.lastname: McClure
authors.forename: Mark B
authors.initials: MB
authors.lastname: Feinberg
authors.forename: Michel
authors.initials: M
authors.lastname: Brahic
authors.forename: Frédéric
authors.initials: F
authors.lastname: Tangy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D015703:Antigens, CD / Q000235:genetics; D001483:Base Sequence; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D007114:Immunization; D008251:Macaca; D008457:Measles / Q000517:prevention & control / Q000821:virology; D008458:Measles Vaccine / Q000235:genetics / Q000276:immunology*; D008459:Measles virus / Q000145:classification / Q000235:genetics*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D014709:Vero Cells
chemical_list: D000914:Antibodies, Viral; D015703:Antigens, CD; C497857:CD46 protein, human; D018076:DNA, Complementary; C497859:Mcp protein, mouse; D008458:Measles Vaccine; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins