Immune Responses to Twice-Annual Influenza Vaccination in Older Adults in Hong Kong

Tam, Yat Hung; Valkenburg, Sophie A.; Perera, Ranawaka A.P.M.; Wong, Jennifer H F; Fang, Vicky J.; Ng, Tuen Wai; Kwong, Anna Ka-Yee; Tsui, Wendy Wing Sze; Ip, Dennis K. M.; Poon, Leo L. M.; Chau, C K V; Barr, Ian G.; Peiris, Malik; Cowling, Benjamin J.

doi:10.1093/cid/cix900

Cited by 24 publications

(24 citation statements)

References 33 publications

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“…Kong proposed that six-monthly vaccination improved protection against circulating seasonal influenza strains. 13 Similar to observations following repeated annual vaccination, the results also raised the concern that more frequent vaccination may actually impair immune responses. 14 Singapore is a tropical city-state, where influenza epidemics typically occur biannually, coinciding with the Northern and Southern hemisphere winters, and endemic virus activity persists year-round.…”

Section: An Observational Study Of Antibody Persistence Conducted Ovesupporting

confidence: 67%

Semiannual Versus Annual Influenza Vaccination in Older Adults in the Tropics: An Observer-blind, Active-comparator–controlled, Randomized Superiority Trial

Young

Sadarangani

Haur

et al. 2018

Clinical Infectious Diseases

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Background: Antibody titres and vaccine effectiveness decline within six months after influenza vaccination in older adults. Biannual vaccination may be necessary to provide year-round protection in the tropics where influenza is present throughout the year. Methods: Tropical Influenza Control Strategies (TROPICS1) was a single-centre, 1:1 randomised, observer-blinded, active-comparator controlled, superiority study in 200 community-resident adults aged ≥65 years. Participants received standard-dose trivalent inactivated influenza vaccination (IIV3) at enrolment, and either tetanus-diphtheria-pertussis vaccination or IIV3 six months later. Primary outcome was the proportion of participants with haemagglutination-inhibition (HI) geometric mean titre (GMT) ≥1:40 one month after the second vaccination (Month 7). Secondary outcomes included GMTs to Month 12, the incidence of influenza-like illness (ILI), and adverse reactions after vaccination. This study is registered with ClinicalTrials.gov: NCT02655874. Findings: At Month 7, the proportion of participants with a HI tire ≥1:40 against A/H1N1 increased by 21•4% (95% CI 8•6-33•4) in the six-monthly vaccination group. This proportion was not significantly higher for A/H3N2 (4•3, 95% CI-1•1-10•8) or B (2•1, 95% CI-2•0-7•3). Six-monthly vaccination significantly increased GMTs against A/H1N1 and A/H3N2 at Month 7, but not B. Participants receiving repeat IIV3 reported a significantly lower incidence of ILI in the six months after the second vaccination (relative vaccine efficacy of 57•1%, 95% CI 0•6-81•5). The frequency of adverse events was similar after first or second influenza vaccination. Interpretation: Six-monthly influenza vaccination in older residents of tropical countries is a simple intervention with the potential for improving protection against infection.

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Section: An Observational Study Of Antibody Persistence Conducted Ovesupporting

confidence: 67%

Semiannual Versus Annual Influenza Vaccination in Older Adults in the Tropics: An Observer-blind, Active-comparator–controlled, Randomized Superiority Trial

Young

Sadarangani

Haur

et al. 2018

Clinical Infectious Diseases

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“…In our study, ADCC activity towards conserved NP, cross‐reactive H7‐HA, seasonal HA and NA proteins was boosted by recent H1N1 infection. Previously, we have reported limited boosting of ADCC responses post‐vaccination with seasonal inactivated vaccines in older adults . Influenza infection exposures in children boost ADCC responses but are less pronounced in adults post‐infection, and similarly cross‐reactive ADCC responses plateau with age by 17 years of age .…”

Section: Discussionmentioning

confidence: 59%

“…Previously, we have reported limited boosting of ADCC responses post-vaccination with seasonal inactivated vaccines in older adults. 11 Influenza infection exposures in children boost ADCC responses but are less pronounced in adults post-infection, 8 and similarly cross-reactive ADCC responses plateau with age by 17 years of age. 7 In addition, we have previously found that ADCC responses in samples from adults collected a few months before and after H1N1 infection are stable.…”

Section: Discussionmentioning

confidence: 99%

“…A protein plate-bound NK ADCC assay was performed as previously described. 11 The assay measures degranulation (CD107a) of activated human NK cells (NK92 cell line transfected with FcRc IIIA, CD16) due to cross-linking of protein-specific IgG in participant sera (Supplementary figure 1). A panel of influenza viral proteins of representative influenza strains and cross-reactive proteins was assessed for ADCC activity.…”

Section: Protein-specific Adcc Responsesmentioning

confidence: 99%

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Cross‐reactive antibody‐dependent cellular cytotoxicity antibodies are increased by recent infection in a household study of influenza transmission

et al. 2019

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Objectives Influenza causes a spectrum of disease from asymptomatic infection to fatal outcome, and pre‐existing immunity can alter susceptibility and disease severity. In a household transmission study, we recruited outpatients with confirmed influenza virus infection and prospectively identified secondary infections in their household contacts, therefore identifying infection cases with baseline samples for determining immune‐mediated protection from influenza infection. Methods We examined baseline broadly reactive immune correlates of relevance to universal vaccine development, specifically antibody‐dependent cytotoxic (ADCC) antibodies and T‐cell responses in functional assays. Antibodies were assessed in a cell‐based NK cell degranulation assay by flow cytometry, and T‐cell responses were assessed by IFN‐γ intracellular cytokine staining flow cytometry assay. Results The magnitude of antibody responses and ADCC function for multiple influenza‐specific proteins was lower in participants who became infected, consolidating the role of pre‐existing antibodies in protection from seasonal influenza virus infection. Among H1N1‐infected contacts, we found that higher levels of pre‐existing H1‐haemagglutinin ADCC responses correlated with reduced symptom severity. Recent infection boosted the titre and magnitude of haemagglutinin‐, neuraminidase‐ and nucleoprotein‐specific ADCC antibodies. Limited T‐cell samples precluded conclusions on the role of pre‐existing T‐cell responses. Conclusions Overall, ADCC responses are a protective correlate against influenza virus infection that should be considered in future vaccine development and evaluation. Influenza‐specific ADCC responses are elevated in uninfected subjects, associated with reduced symptoms and boosted by recent infection, whilst HA stem and NA IgG are also elevated in uninfected participants irrespective of ADCC function.

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“…So far, on the balance of cost e ectiveness and practicality, it is recommended to vaccinate with the most updated strains at the time of presentation. Vaccinating twice a year to cover both the southern and northern winter strains though, theoretically covers all predicted circulating strains, can paradoxically result in lower geometric mean titres of protective antibodies after the 2 nd in uenza vaccine 10 .…”

Section: Immunosenescencementioning

confidence: 99%

Vaccinations in the Elderly

Shen¹,

Yew²

2018

SFP

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The proportion of the elderly in the population has been steadily increasing globally. In Singapore, it is estimated that a quarter of the population will be older than 65 years in 2030. The elderly are more susceptible to infections and once acquired, the infections are often more severe. Effective vaccination has been the most efficient interventional strategy to reduce the morbidity and mortality of infections in the young and greater attention should be paid to the use of vaccinations in the elderly.

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Immune Responses to Twice-Annual Influenza Vaccination in Older Adults in Hong Kong

Cited by 24 publications

References 33 publications

Semiannual Versus Annual Influenza Vaccination in Older Adults in the Tropics: An Observer-blind, Active-comparator–controlled, Randomized Superiority Trial

Semiannual Versus Annual Influenza Vaccination in Older Adults in the Tropics: An Observer-blind, Active-comparator–controlled, Randomized Superiority Trial

Cross‐reactive antibody‐dependent cellular cytotoxicity antibodies are increased by recent infection in a household study of influenza transmission

Vaccinations in the Elderly

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