Preexisting Immunity, Not Frailty Phenotype, Predicts Influenza Postvaccination Titers among Older Veterans

doi:10.1128/CVI.00498-16

Observational Study

. 2017 Mar 6;24(3):e00498-16.

doi: 10.1128/CVI.00498-16. Print 2017 Mar.

Preexisting Immunity, Not Frailty Phenotype, Predicts Influenza Postvaccination Titers among Older Veterans

Puja Van Epps^{1

2}, Terrence Tumpey³, Melissa B Pearce³, Hana Golding⁴, Patricia Higgins^{5

6}, Thomas Hornick^{5

2}, Christopher Burant^{5

6}, Brigid M Wilson⁵, Richard Banks⁵, Stefan Gravenstein⁷, David H Canaday^{5

2}

Affiliations

¹ Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA puja.vanepps@va.gov.
² Department of Internal Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
³ Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
⁴ Division of Viral Products, Center for Biologics Evaluation & Research (CBER), FDA, Silver Spring, Maryland, USA.
⁵ Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA.
⁶ School of Nursing, Case Western Reserve University, Cleveland, Ohio, USA.
⁷ Division of Geriatrics, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.

PMID: 28100496
PMCID: PMC5339642
DOI: 10.1128/CVI.00498-16

Observational Study

Preexisting Immunity, Not Frailty Phenotype, Predicts Influenza Postvaccination Titers among Older Veterans

Puja Van Epps et al. Clin Vaccine Immunol. 2017.

. 2017 Mar 6;24(3):e00498-16.

doi: 10.1128/CVI.00498-16. Print 2017 Mar.

Authors

Affiliations

¹ Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA puja.vanepps@va.gov.
² Department of Internal Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
³ Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
⁴ Division of Viral Products, Center for Biologics Evaluation & Research (CBER), FDA, Silver Spring, Maryland, USA.
⁵ Geriatric Research, Education, and Clinical Center, Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio, USA.
⁶ School of Nursing, Case Western Reserve University, Cleveland, Ohio, USA.
⁷ Division of Geriatrics, Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.

PMID: 28100496
PMCID: PMC5339642
DOI: 10.1128/CVI.00498-16

Abstract

Both preexisting immunity to influenza and age have been shown to be correlates of influenza vaccine responses. Frailty, an indicator of functional impairment in older adults, was also shown in one study to predict lower influenza vaccine responses among nonveterans. In the current study, we aimed to determine the associations between frailty, preexisting immunity, and immune responses to influenza vaccine among older veterans. We studied 117 subjects (age range, 62 to 95 years [median age, 81 years]), divided into three cohorts based on the Fried frailty test, i.e., nonfrail (NF) (n = 23 [median age, 68 years]), prefrail (n = 50 [median age, 80 years]), and frail (n = 44 [median age, 82 years]), during the 2010-2011 and 2011-2012 influenza seasons. Subjects received the seasonal trivalent inactivated influenza vaccine, and baseline and postvaccination samples were obtained. Anti-influenza humoral immunity, as measured by hemagglutination inhibition (HI) and microneutralization assays, was measured for influenza B, A(H1N1)pdm09, and A(H3N2) viruses. Postvaccination titers were not different between frail and NF subjects overall in this older subset of veterans. However, preexisting HI titers were strongly correlated with postvaccination titers among all functional status groups. When microneutralization titers were compared, the association between preexisting immunity and vaccine responses varied by frailty status, with the strongest correlation being observed for the NF group. In conclusion, preexisting immunity rather than frailty appeared to predict postvaccination titers in this older veteran cohort.

Keywords: Frailty; influenza vaccines.

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Figures

**FIG 1**
Comparison of hemagglutination inhibition (HI) (A) and microneutralization (MN) (B) postvaccination/prevaccination geometric mean titer (GMT) ratios within frailty groups. No statistically significant differences, as measured by one-way ANOVA, were found between frailty groups. Horizontal black lines represent the mean, and the vertical lines represent 1 standard deviation (SD).

**FIG 2**
Correlation of preexisting immunity with postvaccination responses, as measured by hemagglutination inhibition (HI) (A) and microneutralization (MN) (B) assays. Antibody levels were plotted within frailty groups, and correlations were calculated to determine the effect of preexisting immunity on postvaccination antibody titers. The Spearman correlation coefficient and P value are presented for each frailty group.

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References

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1. Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. 2003. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 289:179–186. doi:10.1001/jama.289.2.179. - DOI - PubMed
1. Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ, Fukuda K. 2004. Influenza-associated hospitalizations in the United States. JAMA 292:1333–1340. doi:10.1001/jama.292.11.1333. - DOI - PubMed
1. Mullooly JP, Bridges CB, Thompson WW, Chen J, Weintraub E, Jackson LA, Black S, Shay DK. 2007. Influenza- and RSV-associated hospitalizations among adults. Vaccine 25:846–855. doi:10.1016/j.vaccine.2006.09.041. - DOI - PubMed
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[1] Centers for Disease Control and Prevention. 2010. Estimates of deaths associated with seasonal influenza: United States, 1976–2007. MMWR Morb Mortal Wkly Rep 59:1057–1062. - PubMed

[2] Centers for Disease Control and Prevention. 2010. Estimates of deaths associated with seasonal influenza: United States, 1976–2007. MMWR Morb Mortal Wkly Rep 59:1057–1062. - PubMed

[3] Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. 2003. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 289:179–186. doi:10.1001/jama.289.2.179. - DOI - PubMed

[4] Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, Fukuda K. 2003. Mortality associated with influenza and respiratory syncytial virus in the United States. JAMA 289:179–186. doi:10.1001/jama.289.2.179. - DOI - PubMed

[5] Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ, Fukuda K. 2004. Influenza-associated hospitalizations in the United States. JAMA 292:1333–1340. doi:10.1001/jama.292.11.1333. - DOI - PubMed

[6] Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ, Fukuda K. 2004. Influenza-associated hospitalizations in the United States. JAMA 292:1333–1340. doi:10.1001/jama.292.11.1333. - DOI - PubMed

[7] Mullooly JP, Bridges CB, Thompson WW, Chen J, Weintraub E, Jackson LA, Black S, Shay DK. 2007. Influenza- and RSV-associated hospitalizations among adults. Vaccine 25:846–855. doi:10.1016/j.vaccine.2006.09.041. - DOI - PubMed

[8] Mullooly JP, Bridges CB, Thompson WW, Chen J, Weintraub E, Jackson LA, Black S, Shay DK. 2007. Influenza- and RSV-associated hospitalizations among adults. Vaccine 25:846–855. doi:10.1016/j.vaccine.2006.09.041. - DOI - PubMed

[9] Sambhara S, McElhaney JE. 2009. Immunosenescence and influenza vaccine efficacy. Curr Top Microbiol Immunol 333:413–429. doi:10.1007/978-3-540-92165-3_20. - DOI - PMC - PubMed

[10] Sambhara S, McElhaney JE. 2009. Immunosenescence and influenza vaccine efficacy. Curr Top Microbiol Immunol 333:413–429. doi:10.1007/978-3-540-92165-3_20. - DOI - PMC - PubMed

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Preexisting Immunity, Not Frailty Phenotype, Predicts Influenza Postvaccination Titers among Older Veterans

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Preexisting Immunity, Not Frailty Phenotype, Predicts Influenza Postvaccination Titers among Older Veterans

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