title: Do antibody responses to the influenza vaccine persist year-round in the elderly? A systematic review and meta-analysis.
abstract: The influenza vaccine is less immunogenic in older than younger adults, and the duration of protection is unclear. Determining if protection persists beyond a typical seasonal epidemic is important for climates where influenza virus activity is year-round.
  
  
  
  A systematic review protocol was developed and registered with PROSPERO [CRD42015023847]. Electronic databases were searched systematically for studies reporting haemagglutination-inhibition (HI) titres 180-360days following vaccination with inactivated trivalent seasonal influenza vaccine, in adults aged ⩾65years. Geometric mean titre (GMT) and seroprotection (HI titre ⩾1:40) at each time point was extracted. A Bayesian model was developed of titre trajectories from pre-vaccination to Day 360. In the meta-analysis, studies were aggregated using a random-effects model to compare pre-vaccination with post-vaccination HI titres at Day 21-42 ('seroconversion'), Day 180 and Day 360. Potential sources of bias were systematically assessed, and heterogeneity explored.
  
  
  
  2864 articles were identified in the literature search, of which nineteen met study inclusion/exclusion criteria. Sixteen studies contained analysable data from 2565 subjects. In the Bayesian model, the proportion of subjects seroprotected increased from 41-51% pre-vaccination to 75-78% at seroconversion. Seroprotection subsequently fell below 60% for all serotypes by Day 360: A/H1 42% (95% CI 38-46), A/H3 59% (54-63), B 47% (42-52). The Bayesian model of GMT trajectories revealed a similar pattern. By Day 360, titres were similar to pre-vaccination levels. In the meta-analysis, no significant difference in proportion of subjects seroprotected, 0 (-0.11, 0.11) or in log2GMT 0.30 (-0.02, 0.63) was identified by Day 360 compared with pre-vaccination. The quality of this evidence was limited to moderate on account of significant participant dropout.
  
  
  
  The review found consistent evidence that HI antibody responses following influenza vaccination do not reliably persist year-round in older adults. Alternative vaccination strategies could provide clinical benefits in regions where year-round protection is important.
authors.affiliation: Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433 Singapore, Singapore. Electronic address: Barnaby_young@ttsh.com.sg.
authors.forename: Barnaby
authors.initials: B
authors.lastname: Young
authors.affiliation: Saw Swee Hock School of Public Health, Tahir Foundation Building, National University of Singapore, 12 Science Drive 2, #09-01, 117549 Singapore, Singapore.
authors.forename: Xiahong
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Saw Swee Hock School of Public Health, Tahir Foundation Building, National University of Singapore, 12 Science Drive 2, #09-01, 117549 Singapore, Singapore; Yale-NUS College, National University of Singapore, 16 College Avenue West #01-220, 138527 Singapore, Singapore.
authors.forename: Alex R
authors.initials: AR
authors.lastname: Cook
authors.affiliation: School of Tropical Medicine and Global Health, Nagasaki University Institute of Tropical Medicine, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Parry
authors.affiliation: Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433 Singapore, Singapore; Lee Kong Chian School of Medicine, 11 Mandalay Road, 308232 Singapore, Singapore.
authors.forename: Annelies
authors.initials: A
authors.lastname: Wilder-Smith
authors.affiliation: Institute of Infectious Diseases and Epidemiology, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, 308433 Singapore, Singapore; Saw Swee Hock School of Public Health, Tahir Foundation Building, National University of Singapore, 12 Science Drive 2, #09-01, 117549 Singapore, Singapore.
authors.forename: Mark Chen
authors.initials: MC
authors.lastname: I-Cheng
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology*; D009975:Orthomyxoviridae / Q000276:immunology*; D013997:Time Factors
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines
keywords: Elderly; Influenza; Seasonal; Seroprotection; Tropics; Vaccine