title: Prophylactic and therapeutic testing of Nicotiana-derived RSV-neutralizing human monoclonal antibodies in the cotton rat model.
abstract: Severe lower respiratory tract infection in infants and small children is commonly caused by respiratory syncytial virus (RSV). Palivizumab (Synagis(®)), a humanized IgG1 monoclonal antibody (mAb) approved for RSV immunoprophylaxis in at-risk neonates, is highly effective, but pharmacoeconomic analyses suggest its use may not be cost-effective. Previously described potent RSV neutralizers (human Fab R19 and F2-5; human IgG RF-1 and RF-2) were produced in IgG format in a rapid and inexpensive Nicotiana-based manufacturing system for comparison with palivizumab. Both plant-derived (palivizumab-N) and commercial palivizumab, which is produced in a mouse myeloma cell line, showed protection in prophylactic (p < 0.001 for both mAbs) and therapeutic protocols (p < 0.001 and p < 0.05 respectively). The additional plant-derived human mAbs directed against alternative epitopes displayed neutralizing activity, but conferred less protection in vivo than palivizumab-N or palivizumab. Palivizumab remains one of the most efficacious RSV mAbs described to date. Production in plants may reduce manufacturing costs and improve the pharmacoeconomics of RSV immunoprophylaxis and therapy.
authors: Mapp Biopharmaceutical, Inc., San Diego, CA, USA. larry.zeitlin@mappbio.com
authors: Larry
authors: L
authors: Zeitlin
authors: Ognian
authors: O
authors: Bohorov
authors: Natasha
authors: N
authors: Bohorova
authors: Andrew
authors: A
authors: Hiatt
authors: Do H
authors: DH
authors: Kim
authors: Michael H
authors: MH
authors: Pauly
authors: Jesus
authors: J
authors: Velasco
authors: Kevin J
authors: KJ
authors: Whaley
authors: Dale L
authors: DL
authors: Barnard
authors: John T
authors: JT
authors: Bates
authors: James E
authors: JE
authors: Crowe
authors: Pedro A
authors: PA
authors: Piedra
authors: Brian E
authors: BE
authors: Gilbert
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000191:economics / Q000276:immunology / Q000627:therapeutic use*; D057134:Antibodies, Neutralizing / Q000191:economics / Q000276:immunology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D000069455:Palivizumab; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D016205:Sigmodontinae; D014026:Nicotiana / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D057134:Antibodies, Neutralizing; D000069455:Palivizumab
keywords: Nicotiana; RSV; antibody; monoclonal; prophylaxis; therapy
references: Health Technol Assess. 2011 Jan;15(5):iii-iv, 1-124
references: 21281564
references: Ann Oncol. 2010 Dec;21(12):2420-2427
references: 20494963
references: Arch Dis Child. 2010 Jul;95(7):493-8
references: 20504841
references: Pediatr Pulmonol. 2001 Jul;32(1):20-8
references: 11416872
references: Pediatrics. 1997 Jan;99(1):93-9
references: 8989345
references: Plant Biotechnol J. 2010 Jun;8(5):638-54
references: 20514694
references: Lancet. 1999 Aug 14;354(9178):541-5
references: 10470697
references: Nature. 1989 Nov 2;342(6245):76-8
references: 2509938
references: Hum Vaccin. 2011 Mar;7(3):313-21
references: 21346417
references: Am J Med. 1997 Mar 17;102(3A):27-30; discussion 42-3
references: 10868139
references: Blood. 2011 Mar 10;117(10):2755-63
references: 21139081
references: Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1386-90
references: 8108420
references: Eur J Pediatr. 2003 Apr;162(4):237-44
references: 12647196
references: J Infect Dis. 1997 Nov;176(5):1215-24
references: 9359721
references: J Paediatr Child Health. 2000 Oct;36(5):422-7
references: 11036794
references: Pediatrics. 1998 Sep;102(3 Pt 1):648-51
references: 9738192
references: Clin Microbiol Rev. 2000 Jul;13(3):371-84
references: 10885982
references: Plant Biotechnol J. 2008 May;6(4):392-402
references: 18346095
references: Clin Ther. 2000 Nov;22(11):1357-69
references: 11117660
references: Nat Biotechnol. 1998 Dec;16(13):1361-4
references: 9853620
references: Nat Biotechnol. 2005 Jun;23(6):718-23
references: 15883585
references: Pediatrics. 1998 Sep;102(3):531-7
references: 9724660
references: Mol Med. 1999 Jan;5(1):35-45
references: 10072446
references: Proc Natl Acad Sci U S A. 2006 Oct 3;103(40):14645-6
references: 17000998
references: Hum Vaccin. 2011 Mar;7(3):349-56
references: 21358287
references: Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10164-8
references: 1279672
references: Pediatrics. 1999 Sep;104(3 Pt 1):419-27
references: 10469764
references: Vaccine. 1993 Nov;11(14):1415-23
references: 7508665
references: Int Immunol. 2001 Dec;13(12):1551-9
references: 11717196
references: J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Mar 15;848(1):8-18
references: 16899415
references: J Infect Dis. 1999 Aug;180(2):268-77
references: 10395839
references: J Pediatr. 2003 Nov;143(5 Suppl):S127-32
references: 14615711
references: J Paediatr Child Health. 2002 Aug;38(4):352-7
references: 12173995
references: Nat Rev Drug Discov. 2010 Jan;9(1):15-6
references: 20043025
references: J Infect Dis. 1998 Apr;177(4):1073-6
references: 9534985
references: Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20690-4
references: 22143789
references: Virus Res. 2005 Jul;111(1):93-100
references: 15896408