title: Effects of Repeated Annual Inactivated Influenza Vaccination among Healthcare Personnel on Serum Hemagglutinin Inhibition Antibody Response to A/Perth/16/2009 (H3N2)-like virus during 2010-11.
abstract: BACKGROUND
  Recently, lower estimates of influenza vaccine effectiveness (VE) against A(H3N2) virus illness among those vaccinated during the previous season or multiple seasons have been reported; however, it is unclear whether these effects are due to differences in immunogenicity.
  
  
  METHODS
  We performed hemagglutination inhibition antibody (HI) assays on serum collected at preseason, ∼ 30 days post-vaccination, and postseason from a prospective cohort of healthcare personnel (HCP). Eligible participants had medical and vaccination records for at least four years (since July, 2006), including 578 HCP who received 2010-11 trivalent inactivated influenza vaccine [IIV3, containing A/Perth/16/2009-like A(H3N2)] and 209 HCP who declined vaccination. Estimates of the percentage with high titers (≥ 40 and>100) and geometric mean fold change ratios (GMRs) to A/Perth/16/2009-like virus by number of prior vaccinations were adjusted for age, sex, race, education, household size, hospital care responsibilities, and study site.
  
  
  RESULTS
  Post-vaccination GMRs were inversely associated with the number of prior vaccinations, increasing from 2.3 among those with 4 prior vaccinations to 6.2 among HCP with zero prior vaccinations (F[4,567]=9.97, p<.0005). Thirty-two percent of HCP with 1 prior vaccination achieved titers >100 compared to only 11% of HCP with 4 prior vaccinations (adjusted odds ratio=6.8, 95% CI=3.1 - 15.3).
  
  
  CONCLUSIONS
  Our findings point to an exposure-response association between repeated IIV3 vaccination and HI for A(H3N2) and are consistent with recent VE observations. Ultimately, better vaccines and vaccine strategies may be needed in order to optimize immunogenicity and VE for HCP and other repeated vaccinees.
authors.affiliation: Epidemiology and Prevention Branch, Influenza Division/NCIRD/CDC, Atlanta, GA 30333. Electronic address: isq8@cdc.gov.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Thompson
authors.affiliation: The Center for Health Research, Kaiser Permanente Northwest, Portland, OR 97227.
authors.forename: Allison
authors.initials: A
authors.lastname: Naleway
authors.affiliation: Epidemiology and Prevention Branch, Influenza Division/NCIRD/CDC, Atlanta, GA 30333.
authors.forename: Alicia M
authors.initials: AM
authors.lastname: Fry
authors.affiliation: Abt Associates, Cambridge, MA 02138.
authors.forename: Sarah
authors.initials: S
authors.lastname: Ball
authors.affiliation: Epidemiology and Prevention Branch, Influenza Division/NCIRD/CDC, Atlanta, GA 30333.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Spencer
authors.affiliation: Epidemiology and Prevention Branch, Influenza Division/NCIRD/CDC, Atlanta, GA 30333.
authors.forename: Sue
authors.initials: S
authors.lastname: Reynolds
authors.affiliation: The Center for Health Research, Kaiser Permanente Northwest, Portland, OR 97227.
authors.forename: Sam
authors.initials: S
authors.lastname: Bozeman
authors.affiliation: Epidemiology and Prevention Branch, Influenza Division/NCIRD/CDC, Atlanta, GA 30333.
authors.forename: Min
authors.initials: M
authors.lastname: Levine
authors.affiliation: Epidemiology and Prevention Branch, Influenza Division/NCIRD/CDC, Atlanta, GA 30333.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
authors.affiliation: Division of Pediatric Infectious Diseases, Baylor Scott & White Health, Texas A&M HSC COM, Temple, TX 76508.
authors.forename: Manjusha
authors.initials: M
authors.lastname: Gaglani
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006282:Health Personnel; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007251:Influenza, Human / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014611:Vaccination / Q000706:statistics & numerical data*; D015164:Vaccines, Inactivated / Q000008:administration & dosage
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: healthcare personnel; hemagglutination inhibition antibody; immunogenicity; influenza vaccination
references.citation: Open Forum Infect Dis. 2015 Jan 03;2(1):ofu115
references.pmid: 25884004
references.citation: PLoS One. 2008 Aug 20;3(8):e2975
references.pmid: 18714352
references.citation: Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):14001-6
references.pmid: 10570188
references.citation: Clin Infect Dis. 2014 Jan;58(1):50-7
references.pmid: 24046301
references.citation: Vaccine. 2012 May 21;30(24):3557-65
references.pmid: 22475860
references.citation: PLoS One. 2014 Mar 25;9(3):e92153
references.pmid: 24667168
references.citation: Clin Infect Dis. 2013 May;56(10):1363-9
references.pmid: 23413420
references.citation: Vaccine. 1996 Oct;14(14):1331-9
references.pmid: 9004442
references.citation: Influenza Other Respir Viruses. 2011 Jul;5(4):288-95
references.pmid: 21651740
references.citation: Health Psychol. 2014 Mar;33(3):282-91
references.pmid: 23795705
references.citation: MMWR Morb Mortal Wkly Rep. 2013 Feb 22;62(7):119-23
references.pmid: 23425960
references.citation: Clin Vaccine Immunol. 2011 Sep;18(9):1401-5
references.pmid: 21795459
references.citation: PLoS Pathog. 2012;8(7):e1002802
references.pmid: 22829765
references.citation: Clin Infect Dis. 2013 Aug;57(3):474-6
references.pmid: 23619811
references.citation: J Infect Dis. 2011 Dec 15;204(12):1879-85
references.pmid: 21998477
references.citation: BMC Med Res Methodol. 2010 Mar 08;10:18
references.pmid: 20210985
references.citation: J Health Psychol. 2014 Sep;19(9):1185-96
references.pmid: 23682064
references.citation: Adv Immunol. 1968;8:81-127
references.pmid: 4874538
references.citation: Vaccine. 2001 Sep 14;19(32):4610-7
references.pmid: 11535308
references.citation: Clin Infect Dis. 2014 Feb;58(4):449-57
references.pmid: 24280090
references.citation: Vaccine. 1997 Jul;15(10):1114-22
references.pmid: 9269055
references.citation: Vaccine. 2011 Aug 5;29(34):5785-92
references.pmid: 21624411
references.citation: Vaccine. 1996 Aug;14(12):1108-10
references.pmid: 8911005
references.citation: Infect Control Hosp Epidemiol. 2014 May;35(5):538-46
references.pmid: 24709723
references.citation: Arch Intern Med. 1999 Jan 25;159(2):182-8
references.pmid: 9927102
references.citation: Vaccine. 2010 May 21;28(23):3929-35
references.pmid: 20394719
references.citation: Vaccine. 1994 Aug;12(10):947-52
references.pmid: 7975836
references.citation: Virus Res. 2004 Jul;103(1-2):125-32
references.pmid: 15163500
references.citation: MMWR Morb Mortal Wkly Rep. 2010 Aug 27;59(33):1057-62
references.pmid: 20798667
references.citation: J Infect Dis. 2014 Jun 1;209(11):1705-14
references.pmid: 24363436
references.citation: Clin Infect Dis. 2014 Feb;58(3):319-27
references.pmid: 24235265
references.citation: J Infect Dis. 2015 May 15;211(10):1529-40
references.pmid: 25406334
references.citation: Clin Infect Dis. 2014 Nov 15;59(10):1375-85
references.pmid: 25270645
references.citation: J Infect Dis. 2015 May 15;211(10):1519-28
references.pmid: 25416812
references.citation: Vaccine. 2010 May 28;28(24):4079-85
references.pmid: 20399830
references.citation: PLoS Comput Biol. 2012;8(10):e1002741
references.pmid: 23133346
references.citation: J Infect Dis. 1999 Jan;179(1):31-6
references.pmid: 9841819