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Titolo:
TRANSGENIC MICE SECRETING CORONAVIRUS NEUTRALIZING ANTIBODIES INTO THE MILK
Autore:
SOLA I; CASTILLA J; PINTADO B; SANCHEZMORGADO JM; WHITELAW CBA; CLARK AJ; ENJUANES L;
Indirizzi:
CSIC,CTR NACL BIOTECNOL,DEPT MOL & CELL BIOL,CAMPUS UNIV AUTONOMA E-28049 MADRID SPAIN CSIC,CTR NACL BIOTECNOL,DEPT MOL & CELL BIOL E-28049 MADRID SPAIN INST NACL INVEST AGR,DEPT REPROD ANIM MADRID 28040 SPAIN ROSLIN INST,DIV MOL BIOL ROSLIN EH25 9PS MIDLOTHIAN SCOTLAND
Titolo Testata:
Journal of virology
fascicolo: 5, volume: 72, anno: 1998,
pagine: 3762 - 3772
SICI:
0022-538X(1998)72:5<3762:TMSCNA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSMISSIBLE GASTROENTERITIS CORONAVIRUS; PORCINE RESPIRATORY CORONAVIRUS; OVINE BETA-LACTOGLOBULIN; IMMUNOGLOBULIN J-CHAIN; MONOCLONAL-ANTIBODY; GENE-EXPRESSION; ANTIGENIC SITES; E2 GLYCOPROTEIN; SPIKE PROTEIN; MAMMARY-GLAND;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
56
Recensione:
Indirizzi per estratti:
Citazione:
I. Sola et al., "TRANSGENIC MICE SECRETING CORONAVIRUS NEUTRALIZING ANTIBODIES INTO THE MILK", Journal of virology, 72(5), 1998, pp. 3762-3772

Abstract

Ten lines of transgenic mice secreting transmissible gastroenteritis coronavirus (TGEV) neutralizing recombinant monoclonal antibodies (rMAbs) into the milk were generated. The rMAb light-and heavy-chain geneswere assembled by fusing the genes encoding the variable modules of the murine MAb 6A.C3, which binds an interspecies conserved coronavirusepitope essential for virus infectivity, and a constant module from aporcine myeloma with the immunoglobulin A (IgA) isotype. The chimericantibody led to dimer formation in the presence of J chain. The neutralization specific activity of the recombinant antibody produced in transiently or stably transformed cells was 50-fold higher than that of a monomeric rMAb with the IgG1 isotype and an identical binding site. This rMAb had titers of up to 10(4) by radioimmunoassay (RIA) and neutralized virus infectivity up to 10(4)-fold. Of 23 transgenic mice, 17 integrated both light and heavy chains, and at least 10 of them transmitted both genes to the progeny, leading to 100% of animals secreting functional TGEV neutralizing antibody during lactation. Selected mice produced milk with TGEV-specific antibody titers higher than 10(6) as determined by RIA, neutralized virus infectivity by 10(6)-fold, and produced up to 6 mg of antibody per ml. Antibody expression levels were transgene copy number independent and integration site dependent. Comicroinjection of the genomic beta-lactoglobulin gene with rMAb light and heavy-chain genes led to the generation of transgenic mice carrying the three transgenes. The highest antibody titers mere produced by transgenic mice that had integrated the antibody and beta-lactoglobulin genes, although the number of transgenic animals generated does not allow a definitive conclusion on the enhancing effect of beta-lactoglobulin cointegration. This approach may lead to the generation of transgenic animals providing lactogenic immunity to their progeny against enteric pathogens.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 16:51:49