title: A novel influenza virus hemagglutinin-respiratory syncytial virus (RSV) fusion protein subunit vaccine against influenza and RSV.
abstract: Influenza A virus and respiratory syncytial virus (RSV) cause substantial morbidity and mortality afflicting the ends of the age spectrum during the autumn through winter months in the United States. The benefit of vaccination against RSV and influenza using a subunit vaccine to enhance immunity and neutralizing antibody was investigated. Influenza virus hemagglutinin (HA) and RSV fusion (F) protein were tested as vaccine components alone and in combination to explore the adjuvant properties of RSV F protein on HA immunity. Mice vaccinated with HA and F exhibited robust immunity that, when challenged, had reduced viral burden for both influenza and RSV. These studies show an enhancing and cross-protective benefit of F protein for anti-HA immunity.
authors.affiliation: Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Turner
authors.forename: Les P
authors.initials: LP
authors.lastname: Jones
authors.forename: S Mark
authors.initials: SM
authors.lastname: Tompkins
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Tripp
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015153:Blotting, Western; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology / Q000472:pathogenicity*; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D021122:Protein Subunits; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D022261:Respiratory Syncytial Virus Vaccines / Q000627:therapeutic use*; D012136:Respiratory Syncytial Viruses / Q000276:immunology / Q000472:pathogenicity*; D051197:Toll-Like Receptor 4 / Q000502:physiology; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D021122:Protein Subunits; D022261:Respiratory Syncytial Virus Vaccines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014760:Viral Fusion Proteins; C483468:hemagglutinin, human influenza A virus
references.citation: N Engl J Med. 2009 Aug 13;361(7):674-9
references.pmid: 19564633
references.citation: J Infect Dis. 2011 Dec 1;204(11):1692-701
references.pmid: 21998474
references.citation: J Virol. 1994 Aug;68(8):5321-5
references.pmid: 8035532
references.citation: J Clin Microbiol. 1988 Aug;26(8):1595-7
references.pmid: 2459154
references.citation: Immune Netw. 2012 Feb;12(1):8-17
references.pmid: 22536165
references.citation: J Virol. 2003 Sep;77(18):9831-44
references.pmid: 12941892
references.citation: J Virol. 2010 Jan;84(2):1148-57
references.pmid: 19864390
references.citation: Pediatr Infect Dis J. 2000 Nov;19(11):1068-71
references.pmid: 11099087
references.citation: Vaccine. 1989 Dec;7(6):503-5
references.pmid: 2609726
references.citation: Pediatr Infect Dis J. 1996 Jan;15(1):23-31
references.pmid: 8684872
references.citation: J Virol. 1987 Feb;61(2):293-301
references.pmid: 3806789
references.citation: J Infect Dis. 1971 Nov;124(5):449-62
references.pmid: 5115669
references.citation: J Virol. 2010 May;84(9):4277-88
references.pmid: 20181685
references.citation: Vaccine. 2001 Dec 12;20(5-6):954-60
references.pmid: 11738763
references.citation: J Gen Virol. 1989 Oct;70 ( Pt 10):2637-44
references.pmid: 2677234
references.citation: Vaccine. 1994 May;12(6):551-6
references.pmid: 8036830
references.citation: Nat Rev Immunol. 2007 Apr;7(4):267-78
references.pmid: 17363960
references.citation: BMC Public Health. 2009 Sep 24;9:361
references.pmid: 19778430
references.citation: Vaccine. 1993 Nov;11(14):1395-404
references.pmid: 8310760
references.citation: J Gen Virol. 2009 May;90(Pt 5):1119-1123
references.pmid: 19264600
references.citation: Nat Med. 2011 Aug 14;17(9):1132-5
references.pmid: 21841784
references.citation: Int J Infect Dis. 2008 May;12(3):233-8
references.pmid: 17913533
references.citation: J Virol. 2010 Aug;84(16):8132-40
references.pmid: 20519399
references.citation: Pediatr Infect Dis J. 2004 Jan;23(1 Suppl):S65-73
references.pmid: 14730272
references.citation: J Virol. 1999 Sep;73(9):7099-107
references.pmid: 10438795
references.citation: J Infect Dis. 2005 Apr 1;191(7):1093-104
references.pmid: 15747245
references.citation: J Biol Chem. 2010 Sep 10;285(37):28403-9
references.pmid: 20538598
references.citation: Vaccine. 2003 May 1;21(16):1776-9
references.pmid: 12686093
references.citation: Expert Opin Biol Ther. 2011 Nov;11(11):1455-67
references.pmid: 21831008
references.citation: Am Fam Physician. 2011 Jan 15;83(2):141-6
references.pmid: 21243988
references.citation: Med Microbiol Immunol. 1975 Dec 30;162(1):9-14
references.pmid: 1214709
references.citation: PLoS One. 2008 Jan 02;3(1):e1401
references.pmid: 18167560
references.citation: J Infect Dis. 1993 Oct;168(4):1024-9
references.pmid: 8376814
references.citation: Vaccine. 2007 Oct 16;25(42):7422-8
references.pmid: 17850930
references.citation: Vaccine. 1994 Jul;12(9):783-90
references.pmid: 7975856
references.citation: Paediatr Respir Rev. 2003 Jun;4(2):112-9
references.pmid: 12758048
references.citation: Vaccine. 1996 Apr;14(6):478-84
references.pmid: 8782343
references.citation: Nat Immunol. 2000 Nov;1(5):398-401
references.pmid: 11062499
references.citation: J Virol. 2004 Aug;78(16):8753-60
references.pmid: 15280483
references.citation: J Clin Invest. 1998 Feb 1;101(3):643-9
references.pmid: 9449698
references.citation: J Pediatr. 2007 Jul;151(1):34-42, 42.e1
references.pmid: 17586188
references.citation: Vaccine. 1995 Mar;13(4):415-21
references.pmid: 7793140
references.citation: J Virol. 2010 Sep;84(18):9632-6
references.pmid: 20592094
references.citation: J Infect Dis. 2000 Nov;182(5):1331-42
references.pmid: 11010838
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):181-4
references.pmid: 10592220
references.citation: Vaccine. 1997 Jul;15(10):1130-2
references.pmid: 9269057
references.citation: Vaccine. 2003 Jul 28;21(24):3465-7
references.pmid: 12850361
references.citation: Vaccine. 1995 Aug;13(12):1095-101
references.pmid: 7491817
references.citation: Vaccine. 1989 Dec;7(6):533-40
references.pmid: 2692334
references.citation: J Virol. 2011 Aug;85(15):7572-81
references.pmid: 21593156
references.citation: J Pediatr. 2000 Dec;137(6):856-64
references.pmid: 11113844
references.citation: N Engl J Med. 2001 Jun 21;344(25):1917-28
references.pmid: 11419430
references.citation: Vaccine. 1998 Jul;16(11-12):1216-24
references.pmid: 9682382
references.citation: J Gen Virol. 1985 Mar;66 ( Pt 3):409-15
references.pmid: 3838336
references.citation: Vaccine. 2007 Sep 28;25(39-40):6852-62
references.pmid: 17719149
references.citation: Viral Immunol. 2012 Jun;25(3):193-203
references.pmid: 22551066
references.citation: Pediatrics. 1973 Jul;52(1):56-63
references.pmid: 4353352
references.citation: J Infect Dis. 1993 Jan;167(1):191-5
references.pmid: 8418166
references.citation: Vaccine. 1997 Apr;15(5):525-32
references.pmid: 9160520
references.citation: Vaccine. 2000 Mar 6;18(17):1763-72
references.pmid: 10699324
references.citation: J Virol. 1986 Mar;57(3):721-8
references.pmid: 2419587
references.citation: J Clin Invest. 2010 May;120(5):1663-73
references.pmid: 20389023
references.citation: Viral Immunol. 2011 Apr;24(2):131-42
references.pmid: 21449723
references.citation: J Infect Dis. 1994 Dec;170(6):1432-8
references.pmid: 7995982
references.citation: Vaccine. 2002 May 31;20 Suppl 3:S7-12
references.pmid: 12184369
references.citation: J Infect. 2010 Nov;61(5):382-90
references.pmid: 20816695
references.citation: J Clin Microbiol. 1986 Aug;24(2):197-202
references.pmid: 3755730
references.citation: Clin Dev Immunol. 2004 Jun;11(2):113-9
references.pmid: 15330446
references.citation: JAMA. 2004 Sep 15;292(11):1333-40
references.pmid: 15367555
references.citation: Am J Epidemiol. 1969 Apr;89(4):422-34
references.pmid: 4305198
references.citation: J Infect. 2002 Jul;45(1):18-24
references.pmid: 12217726
references.citation: Nature. 1980 Aug 14;286(5774):713-4
references.pmid: 6774260
references.citation: J Infect Dis. 1998 Feb;177(2):467-9
references.pmid: 9466539
references.citation: Br Med J (Clin Res Ed). 1982 Jun 5;284(6330):1665-9
references.pmid: 6805648
references.citation: Nat Immunol. 2001 Aug;2(8):732-8
references.pmid: 11477410
references.citation: Pediatr Infect Dis J. 1994 Sep;13(9):792-8
references.pmid: 7808848
references.citation: Viral Immunol. 2009 Jun;22(3):147-61
references.pmid: 19435411
references.citation: Arch Intern Med. 2002 Jun 10;162(11):1229-36
references.pmid: 12038940
references.citation: Vaccine. 2003 Feb 14;21(9-10):902-14
references.pmid: 12547601
references.citation: PLoS One. 2011;6(7):e21937
references.pmid: 21789196
references.citation: J Virol. 1983 Jul;47(1):171-7
references.pmid: 6345804
references.citation: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13961-6
references.pmid: 9391135
references.citation: N Engl J Med. 2000 Jan 27;342(4):225-31
references.pmid: 10648763
references.citation: Vaccine. 2011 Mar 21;29(14):2568-75
references.pmid: 21300100
references.citation: Annu Int Conf IEEE Eng Med Biol Soc. 2007;2007:5025-8
references.pmid: 18003135
references.citation: Vaccine. 1996 Sep;14(13):1214-8
references.pmid: 8961507
references.citation: Viral Immunol. 2004;17(2):165-81
references.pmid: 15279697
references.citation: Am J Respir Cell Mol Biol. 2002 Mar;26(3):277-82
references.pmid: 11867335
references.citation: PLoS Curr. 2009 Aug 31;1:RRN1025
references.pmid: 20029611
references.citation: Pediatrics. 2009 Dec;124(6):e1072-80
references.pmid: 19933730
references.citation: JAMA. 2003 Jan 8;289(2):179-86
references.pmid: 12517228
references.citation: Vaccine. 1990 Oct;8(5):497-502
references.pmid: 2251875
references.citation: J Immunol. 1995 Sep 15;155(6):2955-9
references.pmid: 7673713
references.citation: J Infect Dis. 1991 Mar;163(3):477-82
references.pmid: 1995720