Evidence map›Paper›PMID 40178253›Full record

Trial reportClinical infectious diseases : an official publication of the Infectious Diseases Society of America2025

Enhanced Influenza Vaccines Extend A(H3N2) Antibody Reactivity in Older Adults but Prior Vaccination Effects Persist.

Annette Fox, Stephany Sánchez-Ovando, Louise Carolan, A Jessica Hadiprodjo, Yuyun Chen, Faith Ho, Samuel M S Cheng, Mark G Thompson, A Danielle Iuliano, Min Z Levine and 6 more

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03330132 (Immunogenicity of Alternative Annual Influenza Vaccination Strategies in Older Adults in Hong Kong - a Randomized Controlled Trial), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03330132 phase4completednot on this map

Immunogenicity of Alternative Annual Influenza Vaccination Strategies in Older Adults in Hong Kong - a Randomized Controlled Trial

TypeinterventionalSponsorThe University of Hong KongRan2017 to 2025Enrolled1,861ConditionsInfluenza, HumanArmsStandard inactivated influenza vaccine (NH formulation), MF 59 adjuvanted inactivated influenza vaccine (NH formulation), High-dose inactivated influenza vaccine (NH formulation), Recombinant hemagglutinin inactivated influenza vaccine (NH formulation)
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Article
  3. Influenza vaccine-specific CD4NPJ vaccines · 2026
    Article
  4. Influenza Vaccine Effectiveness in Australia During 2017-2019.Influenza and other respiratory viruses · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Annette FoxDepartment of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0002-0565-7146
Stephany Sánchez-OvandoDepartment of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0003-1389-2506
Louise CarolanVictorian Infectious Diseases Reference Laboratories, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
A Jessica HadiprodjoDepartment of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Yuyun ChenSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Faith HoSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.ORCID 0000-0002-5640-2223
Samuel M S ChengSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Mark G ThompsonCenters for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Influenza Division, Atlanta, Georgia, USA.
A Danielle IulianoCenters for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Influenza Division, Atlanta, Georgia, USA.
Min Z LevineCenters for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases, Influenza Division, Atlanta, Georgia, USA.ORCID 0000-0002-3197-1649
Sophie A ValkenburgHKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Dennis K M IpSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
J S Malik PeirisSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
Sheena G SullivanDepartment of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Benjamin J CowlingSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.ORCID 0000-0002-6297-7154
Nancy H L LeungSchool of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.ORCID 0000-0001-7314-840X

Funding

Drivers of individual variation in influenza vaccine response and protection from infectionR01AI170116 · NIAID · UNIVERSITY OF CHICAGO · PI Sarah Cobey, John S Tsang · 2022 to 2026
$7.2M
Australian Government Department of HealthHealth and Medical Research Fund 07210157Health and Medical Research Fund Research Fellowship Scheme 07210157Health Bureau of the Hong Kong Special Administrative RegionNIAID NIH HHS R01 AI170116Research Grants Council of the Hong Kong Special Administrative RegionTheme-based Research Scheme T11-712/19-NUniversity Grants Committee of Hong Kong SRFS2021-7S03US Centers for Disease Control and Prevention IP001064-02
6 · The paper itself

Abstract

backgroundInfluenza vaccine effectiveness can be reduced in older adults and among repeatedly vaccinated groups. Results from year 1 of "PIVOT," a randomized trial among adults aged ≥65 years in Hong Kong, showed that adjuvanted (Adj), high-dose (HD), and recombinant hemagglutinin (rHA) vaccines induced greater antibody responses against vaccine viruses than standard-dose (SD) influenza vaccine. Here, we examine the breadth of A(H3N2)-reactive antibodies induced during the first 2 study years (2017/2018, 2018/2019), and compare participants who received influenza vaccination annually, or not at all, for 5 years preceding enrollment.

methods14-20 PIVOT participants per vaccine and prior vaccination group (0/5 or 5/5 prior years) who provided sera on days 0, 30, and 182 in year 1 and days 0 and 30 in year 2 were assessed. Hemagglutination inhibition (HAI) antibody titers were measured against 30 viruses spanning 1968 to 2018.

resultsIn year 1, rHA and Adj but not HD vaccines induced titers ≥40 and titer rises ≥4-fold (seroconversion) against significantly more strains than SD vaccine among participants vaccinated 0/5 prior years. Only rHA and Adj vaccines induced titers ≥40 against post-vaccine strains. Antibody responses were poor among participants vaccinated 5/5 compared with 0/5 prior years and only rHA increased the breadth of seroconversion compared with the SD vaccine in this group. Antibody responses were weaker across groups in year 2.

conclusionsThe results suggest that Adj and particularly rHA vaccines may improve the breadth of protection against A(H3N2) viruses but may not overcome attenuating effects of repeated vaccination in older adults. CLINICAL TRIALS REGISTRATION: NCT03330132.

Indexed as

Antibodies, ViralInfluenza A Virus, H3N2 SubtypeInfluenza, HumanInfluenza VaccinesAgedAged, 80 and overFemaleHemagglutination Inhibition TestsHong KongHumansMaleVaccinationVaccine EfficacyAntibodies, ViralInfluenza Vaccinesimmunogenicityinfluenzaolder adultspublic healthvaccination

Identifiers

PMID40178253
PMCPMC12596410

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.