title: Immunobiology of influenza vaccines.
abstract: Vaccination is the primary strategy for prevention and control of influenza. The surface hemagglutinin (HA) protein of the influenza virus contains two structural elements (head and stalk) that differ in their potential utility as vaccine targets. The head of the HA protein is the primary target of antibodies that confer protective immunity to influenza viruses. The underlying health status, age, and gene polymorphisms of vaccine recipients and, just as importantly, the extent of the antigenic match between the viruses in the vaccine and those that are circulating modulate influenza vaccine protection. Vaccine adjuvants and live attenuated influenza vaccine improve the breadth of immunity to seasonal and pandemic virus strains. Eliciting antibodies against the conserved HA stem region that cross-react with HAs within influenza virus types or subtypes would allow for the development of a universal influenza vaccine. The highly complex network of interactions generated after influenza infection and vaccination can be studied with the use of systems biology tools, such as DNA microarray chips. The use of systems vaccinology has allowed for the generation of gene expression signatures that represent key transcriptional differences between asymptomatic and symptomatic host responses to influenza infection. Additionally, the use of systems vaccinology tools have resulted in the identification of novel surrogate gene markers that are predictors of the magnitude of host responses to vaccines, which is critical to both vaccine development and public health. Identifying associations between variations in vaccine immune responses and gene polymorphisms is critical in the development of universal influenza vaccines.
authors: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD. Electronic address: gomezmm@niaid.nih.gov.
authors: Margarita M
authors: MM
authors: Gomez Lorenzo
authors: National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
authors: Matthew J
authors: MJ
authors: Fenton
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D056738:Cross Protection / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007252:Influenza Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control*; D011110:Polymorphism, Genetic; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines
references: Proc Natl Acad Sci U S A. 2000 May 23;97(11):6108-13
references: 10801978
references: Curr Top Microbiol Immunol. 2009;333:227-41
references: 19768409
references: J Clin Invest. 2011 Aug;121(8):3109-19
references: 21785218
references: N Engl J Med. 2010 Nov 18;363(21):2036-44
references: 21083388
references: Vaccine. 1997 Jul;15(10):1114-22
references: 9269055
references: J Clin Invest. 2010 May;120(5):1663-73
references: 20389023
references: BioDrugs. 2006;20(6):335-40
references: 17176120
references: JAMA. 1962 Oct 6;182:11-3
references: 13883724
references: Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2927-32
references: 21270336
references: Nature. 2002 Nov 14;420(6912):206-10
references: 12432404
references: Clin Infect Dis. 2006 Nov 1;43(9):1135-42
references: 17029131
references: Nat Med. 2012 Mar 06;18(3):327
references: 22395678
references: Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10501-6
references: 18650390
references: Nat Immunol. 2011 Jul 10;12(8):786-95
references: 21743478
references: Proc Natl Acad Sci U S A. 2009 May 12;106(19):7962-7
references: 19416838
references: J Virol. 2010 Jan;84(1):44-51
references: 19864389
references: JAMA. 1999 Mar 10;281(10):908-13
references: 10078487
references: Immunity. 2010 Oct 29;33(4):516-29
references: 21029962
references: Am J Epidemiol. 1982 Aug;116(2):212-27
references: 7114033
references: Curr Top Microbiol Immunol. 2001;260:171-90
references: 11443873
references: Lancet. 1999 Oct 9;354(9186):1277-82
references: 10520648
references: Vaccine. 2005 Jan 11;23(8):1029-36
references: 15620476
references: PLoS Genet. 2011 Aug;7(8):e1002234
references: 21901105
references: Influenza Other Respir Viruses. 2013 Jan;7(1):55-65
references: 22405557
references: N Engl J Med. 2009 Nov 12;361(20):1945-52
references: 19745214
references: J Exp Med. 2011 Jan 17;208(1):181-93
references: 21220454
references: PLoS One. 2009 Nov 12;4(11):e7790
references: 19915662
references: Lancet. 2007 Aug 18;370(9587):580-9
references: 17707753
references: Nat Immunol. 2009 Jan;10(1):116-125
references: 19029902
references: Vaccine. 2002 Dec 20;20 Suppl 5:B17-23
references: 12477413
references: Vaccine. 1993;11(3):293-306
references: 8447157
references: Viral Immunol. 2002;15(2):295-323
references: 12081014
references: OMICS. 2011 Sep;15(9):625-36
references: 21732819
references: Emerg Infect Dis. 2006 Jan;12(1):81-7
references: 16494722
references: Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9047-52
references: 22615367
references: J Infect Dis. 1970 Jul-Aug;122(1):16-25
references: 5433709
references: Clin Ther. 2010 Dec;32(13):2186-97
references: 21316535
references: J Clin Invest. 1937 Mar;16(2):237-43
references: 16694474
references: Nat Med. 2010 Dec;16(12):1389-91
references: 21135852
references: J Virol. 2010 Feb;84(3):1489-503
references: 19923177
references: MMWR Recomm Rep. 2010 Aug 6;59(RR-8):1-62
references: 20689501
references: Nat Rev Microbiol. 2005 Apr;3(4):281-94
references: 15806094
references: PLoS One. 2009;4(2):e4384
references: 19197383
references: Blood. 2007 Mar 1;109(5):2066-77
references: 17105821
references: J Virol. 2010 Apr;84(7):3201-9
references: 20071572
references: Science. 2011 Aug 12;333(6044):850-6
references: 21798894
references: Vaccine. 2010 Aug 31;28 Suppl 3:C25-36
references: 20713254
references: Virus Res. 2004 Jul;103(1-2):173-6
references: 15163506
references: Vaccine. 2012 Jun 19;30(29):4341-8
references: 22682289
references: J Infect Dis. 2011 Apr 1;203(7):921-9
references: 21357945
references: Vaccine. 2005 Jul 8;23 Suppl 1:S26-38
references: 16026906
references: Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5598-603
references: 15034168
references: J Virol. 1998 Nov;72(11):8682-9
references: 9765409
references: J Virol. 2010 May;84(9):4611-8
references: 20181720
references: J Hyg (Lond). 1972 Dec;70(4):767-77
references: 4509641
references: Expert Rev Vaccines. 2009 Apr;8(4):469-81
references: 19348562
references: Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11709-12
references: 19597152
references: Epidemiol Infect. 1989 Apr;102(2):325-33
references: 2703026
references: J Infect Dis. 2006 Nov 1;194 Suppl 2:S111-8
references: 17163383
references: Sci Transl Med. 2011 Jun 1;3(85):85ra48
references: 21632986
references: Postgrad Med J. 1973 Mar;49(569):159-63
references: 4803439
references: Nat Immunol. 2006 May;7(5):449-55
references: 16622432
references: Vaccine. 2011 Mar 16;29(13):2461-73
references: 21256188
references: PLoS One. 2010 Mar 23;5(3):e9812
references: 20352112
references: Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11169-74
references: 21690334
references: Front Immunol. 2011 Dec 16;2:76
references: 22566865
references: Scand J Immunol. 2004 Jan;59(1):1-15
references: 14723616
references: Vaccine. 2008 Sep 12;26 Suppl 4:D35-40
references: 19230157
references: Cell Host Microbe. 2009 Sep 17;6(3):207-17
references: 19664979
references: J Allergy Clin Immunol. 2011 Jan;127(1):130-7, 137.e1-3
references: 21145578
references: Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10736-41
references: 12149435