Interseason waning of vaccine-induced hemagglutination inhibition antibody titers and contributing factors to pre-existing humoral immunity against influenza in community-dwelling older adults 75 years and older

Bettina Wunderlich; Thomas Laskow; Huifen Li; Li Zhang; Engle Abrams; Jing Tian; Jun Yu; Yiyin Chen; Juliette Tavenier; Yushu Huang; Kawsar Talaat; Jay H Bream; Qian-Li Xue; Graham Pawelec; Sean X Leng

doi:10.1186/s12979-023-00362-8

Interseason waning of vaccine-induced hemagglutination inhibition antibody titers and contributing factors to pre-existing humoral immunity against influenza in community-dwelling older adults 75 years and older

Immun Ageing. 2023 Jul 31;20(1):38. doi: 10.1186/s12979-023-00362-8.

Authors

Bettina Wunderlich^{1

2}, Thomas Laskow^{3

4}, Huifen Li^{3

4}, Li Zhang⁵, Engle Abrams^{3

4}, Jing Tian³, Jun Yu^{3

4}, Yiyin Chen^{3

4}, Juliette Tavenier⁶, Yushu Huang⁷, Kawsar Talaat^{1

2}, Jay H Bream^{8

9}, Qian-Li Xue³, Graham Pawelec^{10

11}, Sean X Leng^{12

13

14}

Affiliations

¹ Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
² Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
³ Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins Center On Aging and Immune Remodeling, Johns Hopkins University School of Medicine and Bloomberg School of Public Health, JHAAC Room 1A.38A, 5501 Hopkins Bayview Circle, Baltimore, MD, 21224, USA.
⁵ Department of Geriatrics, The First People's Hospital of Yunnan Province, Kunming, China.
⁶ Department of Clinical Research, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark.
⁷ Vassar College, Poughkeepsie, NY, USA.
⁸ Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
⁹ Immunology Training Program, Johns Hopkins School of Medicine, Baltimore, MD, USA.
¹⁰ Department of Immunology, University of Tübingen, Tübingen, Germany.
¹¹ Health Sciences North Research Institute, Sudbury, ON, Canada.
¹² Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. sleng1@jhu.edu.
¹³ Division of Geriatric Medicine and Gerontology, Department of Medicine, Johns Hopkins Center On Aging and Immune Remodeling, Johns Hopkins University School of Medicine and Bloomberg School of Public Health, JHAAC Room 1A.38A, 5501 Hopkins Bayview Circle, Baltimore, MD, 21224, USA. sleng1@jhu.edu.
¹⁴ Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. sleng1@jhu.edu.

Abstract

Background: Seasonal influenza causes significant morbidity and mortality with a disproportionately high disease burden in older adults. Strain-specific hemagglutination-inhibition (HAI) antibody titer is a well-established measure of humoral immunity against influenza and pre-vaccination HAI titer is a valuable indicator of pre-existing humoral immunity at the beginning of each influenza season in highly vaccinated older adults. While vaccine-induced HAI antibody titers are known to wane over time, accurate assessment of their interseason waning has been challenging. This is because pre-vaccination HAI titers are routinely measured using current season vaccine strain antigens instead of the prior season vaccines with which individuals were immunized; as such, they do not accurately represent residual antibody titers from prior season vaccination. This study took advantage of available pre-vaccination HAI titers measured using both current and prior season vaccine strain antigens in a longitudinal influenza immunization study with participants enrolled for multiple consecutive influenza seasons from 2014 through 2017. Influenza A virus (IAV) H3N2 and influenza B virus (IBV) strains in the vaccine formula changed in 2015 and again in 2016 season. IAV H1N1 vaccine strain remained the same from 2014 through 2016 seasons, but changed in 2017. We also investigated factors contributing to pre-existing humoral immunity.

Results: Interseason waning of HAI titers was evident, but rates of waning varied among vaccine strains and study seasons, from 18% (p = .43) to 61% (p < .01). Rates of waning were noticeably greater when pre-vaccination HAI titers were measured by the routine approach, i.e., using current season vaccine strain antigens, from 33% (p = .12) to 83% (p < .01), adjusting for age at prior study season, sex, race, and education. This was largely because the routinely measured pre-vaccination HAI titers underrepresented residual HAI titers from prior season vaccinations. Moreover, interseason antibody waning and prior season post-vaccination HAI titers had significant and independent associations with pre-vaccination HAI titers.

Conclusions: The routinely measured pre-vaccination HAI titer overestimates interseason HAI antibody waning as it underestimates residual antibody titers from prior season vaccination when virus strains in the vaccine formula change. Moreover, interseason antibody waning and prior season post-vaccination HAI titers independently contribute to pre-existing humoral immunity in this highly vaccinated, community-dwelling older adult population.

Keywords: HAI antibody titer; Influenza vaccination; Interseason antibody waning; Older adults; Pre-existing humoral immunity.

Abstract

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