Influenza vaccine effectiveness against laboratory-confirmed influenza in a vaccine-mismatched influenza B-dominant season

BackgroundThe 2017–2018 influenza season in Israel was characterized by the predominance of influenza B Yamagata, with a lesser circulation of influenza A(H1N1)pdm09 and influenza A(H3N2). We estimated vaccine effectiveness (VE) of the inactivated influenza vaccine which was selected for use that season.MethodsEnd-of-season VE and 95% confidence intervals (CI) against laboratory-confirmed influenza-like illness (ILI) were estimated by means of the test-negative design. Age-specific VE analysis was carried out using a moving age interval.ResultsSpecimen were obtained from 1,453 community ILI patients; 610 (42.0%) were influenza-positive, among which 69.7% were B, 17.2% A(H1N1)pdm09 and 13.4% A(H3N2). A 98.6% of molecularly characterized influenza B belonged to the Yamagata lineage. Of the sampled individuals, 1320 were suitable for VE analysis. Of those vaccinated, 90.6% received the inactivated trivalent influenza vaccine (TIV) containing a Victoria lineage influenza B-like virus. VE against influenza A differed by age, with the highest VE of 72.9% (95%CI 31.9–89.2%) observed in children 0.5–14 years old, while all ages VE was 46.6% (95%CI 10.4–68.2%). All ages VE against influenza B was 23.2% (95%CI −10.1–46.4%) with age-specific analysis showing non-significant VE estimates. Utilizing a moving age interval of 15 years, afforded a detailed age-specific insight into influenza VE against the influenza viruses circulating during the 2017–2018 season.ConclusionsThe moderate-high 2017–2018 influenza A VE among children and adolescents, supports seasonal influenza vaccination at a young age. The low VE against influenza B in Israel, is most likely the result of influenza B/TIV-mismatch.     

The 2015–2016 influenza epidemic in Beijing,China: Unlike elsewhere,circulation of influenza A(H3N2) with moderate vaccine effectiveness

BackgroundWhile the 2015–2016 influenza season in the northern hemisphere was dominated by A(H1N1)pdm09 and B/Victoria viruses, in Beijing, China, there was also significant circulation of influenza A(H3N2) virus. In this report we estimate vaccine effectiveness (VE) against influenza A(H3N2) and other circulating viruses, and describe further characteristics of the 2015–2016 influenza season in Beijing.MethodsWe estimated VE of the 2015–2016 trivalent inactivated vaccine (TIV) against laboratory-confirmed influenza virus infection using the test-negative study design. The effect of prior vaccination on current VE was also examined.ResultsOf 11,000 eligible patients included in the study, 2969 (27.0%) were influenza positive. Vaccination coverage was 4.2% in both cases and controls. Adjusted VE against all influenza was 8% (95% CI: −16% to 27%): 18% (95% CI: −38% to 52%) for influenza A(H1N1)pdm09, 54% (95% CI: 16% to 74%) for influenza A(H3N2), and −8% (95% CI: −40% to 18%) for influenza B/Victoria. The overall VE for receipt of 2015–2016 vaccination only, 2014–2015 vaccination only, and vaccinations in both seasons was −15% (95% CI: −63% to 19%), −25% (95% CI: −78% to 13%), and 18% (95% CI: −11% to 40%), respectively.ConclusionsOverall the 2015–2016 TIV was protective against influenza infection in Beijing, with higher VE against the A(H3N2) viruses compared to A(H1N1)pdm09 and B viruses.     

Influenza vaccine effectiveness against influenza-associated hospitalization in 2015/16 season,Beijing, China

BackgroundVaccination is recommended to prevent influenza virus infection and associated complications. This study aimed to estimate the influenza vaccine effectiveness (VE) against hospitalization in the 2015/16 season in Beijing.MethodsPatients who were hospitalized in the 5 study hospitals between 1 Oct 2015 and 15 May 2016 were recruited. Influenza vaccination status was obtained for PCR-confirmed influenza patients and the selected controls who tested negative for the virus. Conditional logistic regression was used to estimate the influenza VE matching by calendar week, and adjusting for age, study sites, underlying medical conditions, smoking status, and hospital admissions over the past 12 months.ResultsThe overall VE was −37.9% (95% CI: −103.3, 6.5) against laboratory-confirmed influenza-associated hospitalization. The 2015–16 seasonal vaccine was had −61.9% (95% CI: −211.9, 15.9), −5.4% (95% CI: −108.1, 46.6) and −45.2% (95% CI: −152.6, 16.5) effectiveness to prevent infection from A(H1N1)pdm09, A(H3N2) and influenza B, respectively.ConclusionsInfluenza vaccination did not show effective protection against hospitalization with influenza in 2015/16 season in Beijing.     

Influenza vaccine effectiveness against hospitalization with laboratory-confirmed influenza in Greece: A pooled analysis across six seasons, 2013–2014 to 2018–2019

BackgroundMonitoring seasonal influenza Vaccine Effectiveness (VE) is key to inform vaccination strategies and sustain uptake. Pooling data across multiple seasons increases precision and allows for subgroup analyses, providing more conclusive evidence. Our aim was to assess VE against hospitalization with laboratory-confirmed influenza in Greece over six seasons, from 2013 to 2014 to 2018–2019, using routinely collected surveillance data.MethodsSwab samples from hospitalized patients across the country were tested for influenza by RT-PCR. We used the test-negative design, with patients testing positive for influenza serving as cases and those testing negative serving as controls. VE was calculated as one minus the Odds Ratio (OR) for influenza vaccination, estimated by mixed-effects logistic regression and adjusted for age, sex, hospitalization type (being in intensive care or not), time from symptom onset to swabbing, and calendar time. Stratified estimates by age and hospitalization type were obtained, and also subgroup estimates by influenza type/subtype and season. Antigenic and genetic characterization of a subset of circulating influenza strains was performed.ResultsA total of 3,882 test-positive cases and 5,895 test-negative controls were analyzed. Across all seasons, adjusted VE was 45.5% (95% CI: 31.6–56.6) against all influenza, 62.8% against A(H1N1)pdm09 (95% CI: 40.7–76.7), 28.2% against A(H3N2) (95% CI: 12.0–41.3) and 45.5% against influenza B (95% CI: 29.1–58.1). VE was slightly lower for patients aged 60 years and over, and similar between patients hospitalized inside or outside intensive care. Circulating A(H1N1)pdm09 and B strains were antigenically similar to the vaccine strains, whereas A(H3N2) were not.ConclusionOur results confirm the public health benefits from seasonal influenza vaccination, despite the suboptimal effectiveness against A(H3N2) strains. Continued monitoring of VE is essential, and routinely collected surveillance data can be valuable in this regard.     

Lineage-matched versus mismatched influenza B vaccine effectiveness following seasons of marginal influenza B circulation

BackgroundSeveral countries have recently transitioned from the trivalent inactivated influenza vaccine (TIV) to the quadrivalent inactivated influenza vaccine (QIV) in order to outweigh influenza B vaccine-mismatch. However, few studies thus far evaluated its benefits versus the TIV in a systematic manner. Our objective was to compare the QIV VE with lineage-mismatched TIV VE.MethodsWe estimated the 2015–2016, 2017–2018, 2019–2020 end-of season influenza B VE against laboratory-confirmed influenza-like illness (ILI) among community patients, using the test-negative design. VE was estimated for pre-determined age groups and for moving age intervals of 15 years.ResultsSince 2011–2012 season, alternate seasons in Israel were dominated by influenza B circulation. Compared with the lineage-mismatched TIV used during the 2015–2016 and 2017–2018 seasons, the 2019–2020 QIV showed the highest all-ages VE, with VE estimates of 56.9 (95% CI 30.1 to 73.4), 16.5 (95% CI –22.5 to 43.1) and ?25.8 (95% CI ?85.3 to 14.6) for the 2019–2020, 2017–2018 and 2015–2016 seasons, respectively. The 2019–2020 VE point estimated were the highest for the 0.5–4, 5–17 and 18–44 years age groups and for more 15-year age intervals as compared to the other seasons.ConclusionsOur results support the rapid transition from the TIV to the QIV.     

Safety and immunogenicity of a seasonal quadrivalent influenza vaccine (GC3110A) in healthy participants aged ≥ 65 years

BackgroundSeasonal Influenza is still considered associated with seasonal morbidity and hospitalization in the elderly population. The World Health Organization (WHO) recommended seasonal quadrivalent influenza vaccine (QIV) to reduce burden of two currently circulating influenza B lineages. Until 2019 Korean National Immunization Program (NIP) recommended trivalent influenza vaccine (TIV) after ongoing debates on cost effectiveness of QIV for elderly population. Although influenza vaccine only showed modest effect on reducing influenza in elderly, this study aimed to evaluate the immunogenicity and safety of inactivated QIV in healthy participants ≥ 65 years of age.MethodsA total of 274 healthy participants aged ≥ 65 years received a QIV. Seroconversion-based vaccine efficacy of 4 strains of seasonal influenza was assessed 21 days after vaccination and adverse events were monitored until 180 days after vaccination.ResultsThe percentages of participants seroconverted after vaccination on HI antibody against each strain were 36.5% (99/271) to A/H1N1, 47.6% (129/271) to A/H3N2, 40.6% (110/271) to B Yamagata, and 49.1% (133/271) to B Victoria. The percentages of participants seroprotected after vaccination on HI antibody against each strain were 81.2% (220/271) to A/H1N1, 98.5% (267/271) to A/H3N2, 95.2% (258/271) to B Yamagata, and 93.7% (254/271) to B Victoria. There was no serious adverse event (SAE) related with the study vaccine.ConclusionThe quadrivalent split influenza vaccine is expected to offer seroprotection against influenza A and both influenza B lineages even in the elderly population.     

Variable seasonal influenza vaccine effectiveness across geographical regions,age groups and levels of vaccine antigenic similarity with circulating virus strains: A systematic review and meta-analysis of the evidence from test-negative design studies after the 2009/10 influenza pandemic

BackgroundWe examined the influence of some factors on seasonal influenza vaccine effectiveness (VE) from test-negative design (TND) studies.MethodsWe systematically searched for full-text publications of VE against laboratory-confirmed influenza from TND studies in outpatient settings after the 2009/10 influenza pandemic. Two reviewers independently selected and extracted data from the included studies. We calculated pooled adjusted VE across geographical regions, age groups and levels of vaccine antigenic similarity with circulating virus strains, using an inverse variance, random-effects model.ResultsWe included 76 full-text articles from 11,931 citations. VE estimates against A(H1N1)pdm09, A(H3N2), influenza B, and all influenza were homogenous and point pooled VE higher in the Southern hemisphere compared with the Northern hemisphere. The difference in pooled VE between the Southern and Northern hemispheres was statistically significant for A(H3N2), influenza B, and all influenza. A consistent pattern was observed in pooled VE across both hemispheres and continents, with the highest point pooled VE being against A(H1N1)pdm09, followed by influenza B, and lowest against A(H3N2). A nearly consistent pattern was observed in pooled VE across age groups in the Northern hemisphere, with pooled VE mostly decreasing with age. Point pooled VE against A(H3N2), influenza B, and all influenza were statistically significantly higher when vaccine was antigenically similar to circulating virus strains compared with when antigenically dissimilar. Similar pattern was observed in the Northern hemisphere, but there was a lack of data from the Southern hemisphere.ConclusionConsistent patterns appear to exist in seasonal influenza VE across regions, age groups, and levels of vaccine antigenic similarity with circulating virus strains, with best vaccine performance against A(H1N1)pdm09 and worst against A(H3N2). The evidence highlights the need to consider geographical location, age, and vaccine antigenic similarity with circulating virus strains when designing and evaluating influenza VE studies.     

Influenza vaccine effectiveness in preventing laboratory-confirmed influenza in outpatient settings: A test-negative case-control study in Beijing,China, 2016/17 season

BackgroundThe objective of this study was to estimate influenza vaccine effectiveness (VE) for the 2016/17 epidemic of co-circulating influenza A(H1N1)pdm09 and A(H3N2) viruses in Beijing, the capital of China.MethodsThe surveillance-based study included all swabbed patients through influenza virological surveillance, between November 2016 and April 2017. A test-negative case-control design was used to estimate influenza VE against medically-attended laboratory-confirmed influenza in outpatient settings. Cases were influenza-like illness (ILI) patients who tested positive for influenza, and controls were influenza negative patients.ResultsA total of 10,496 ILI patients were enrolled and swabbed. Among them, 735 tested positive for influenza A(H1N1)pdm09, 1851 for A(H3N2), and 40 for type B. Of the 45 randomly selected specimens out of 1851 influenza A(H3N2) viruses, 2(4.4%) belonged to the H3N2 3C.2a1 clade, and 43(95.6%) belonged to A/Hong Kong/4801/2014-like 3C.2a clade. Among the 43 viruses of the 3C.2a clade, 32 viruses clustered in one subgroup carrying T131K, R142K and R261Q substitutions. The adjusted VE against all influenza was low at 25% (95% confidence interval (CI): 0–43%), with 54% (95%CI: 22–73%) for influenza A(H1N1)pdm09, and 2% (95%CI: −35% to 29%) for influenza A(H3N2).ConclusionsOur study suggested a moderate VE against influenza A(H1N1)pdm09, but low VE against influenza A(H3N2) in Beijing, 2016/17 season. Amino acid substitutions in the hemagglutinin may contribute to the low VE against influenza A(H3N2) for this season.     

Understanding influenza vaccine protection in the community: An assessment of the 2013 influenza season in Victoria,Australia

BackgroundThe influenza virus undergoes frequent antigenic drift, necessitating annual review of the composition of the influenza vaccine. Vaccination is an important strategy for reducing the impact and burden of influenza, and estimating vaccine effectiveness (VE) each year informs surveillance and preventative measures. We aimed to describe the influenza season and to estimate the effectiveness of the influenza vaccine in Victoria, Australia, in 2013.MethodsRoutine laboratory notifications, general practitioner sentinel surveillance (including a medical deputising service) data, and sentinel hospital admission surveillance data for the influenza season (29 April to 27 October 2013) were collated in Victoria, Australia, to describe influenza-like illness or confirmed influenza during the season. General practitioner sentinel surveillance data were used to estimate VE against medically-attended laboratory confirmed influenza. VE was estimated using the case test negative design as 1 − adjusted odds ratio (odds of vaccination in cases compared with controls) × 100%. Cases tested positive for influenza while non-cases (controls) tested negative. Estimates were adjusted for age group, week of onset, time to swabbing and co-morbidities.ResultsThe 2013 influenza season was characterised by relatively low activity with a late peak. Influenza B circulation preceded that of influenza A(H1)pdm09, with very little influenza A(H3) circulation. Adjusted VE for all influenza was 55% (95%CI: −11, 82), for influenza A(H1)pdm09 was 43% (95%CI: −132, 86), and for influenza B was 56% (95%CI: −51, 87) Imputation of missing data raised the influenza VE point estimate to 64% (95%CI: 13, 85).ConclusionsClinicians can continue to promote a positive approach to influenza vaccination, understanding that inactivated influenza vaccines prevent at least 50% of laboratory-confirmed outcomes in hospitals and the community.     

Influenza vaccine effectiveness in Italy: Age,subtype-specific and vaccine type estimates 2014/15 season

The 2014/15 influenza season in Europe was characterised by the circulation of influenza A(H3N2) viruses with an antigenic and genetic mismatch from the vaccine strain A/Texas/50/2012(H3N2) recommended for the Northern hemisphere for the 2014/15 season. Italy, differently from other EU countries where most of the subtyped influenza A viruses were H3N2, experienced a 2014/15 season characterized by an extended circulation of two influenza viruses: A(H1N1)pdm09 and A(H3N2), that both contributed substantially to morbidity.Within the context of the existing National sentinel influenza surveillance system (InfluNet) a test-negative case-control study was established in order to produce vaccine effectiveness (VE) estimates. The point estimates VE were adjusted by age group (<5; 5–15; 15–64; 65+ years), the presence of at least one chronic condition, target group for vaccination and need help for walking or bathing. In Italy, adjusted estimates of the 2014/15 seasonal influenza VE against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza for all age groups were 6.0% (95%CI: −36.5 to 35.2%), 43.6% (95%CI: −3.7 to 69.3%), −84.5% (95%CI: (−190.4 to −17.2%) and 50.7% (95% CI: −2.5 to 76.3%) against any influenza virus, A(H1N1)pdm09, A(H3N2) and B, respectively. These results suggest evidence of good VE against A(H1N1)pdm09 and B viruses in Italy and evidence of lack of VE against A(H3N2) virus due to antigenic and genetic mismatch between circulating A(H3N2) and the respective 2014/15 vaccine strain.     

Effectiveness of trivalent inactivated influenza vaccine among community-dwelling older adults in Thailand: A two-year prospective cohort study

Background

We conducted a two-year prospective cohort study to measure the effectiveness of trivalent inactivated influenza vaccine (IIV3) to prevent laboratory-confirmed influenza among community-dwelling Thai adults aged ≥65?years during 2015–16 and 2016–17 influenza seasons.

Effectiveness of subunit influenza vaccination in the 2014–2015 season and residual effect of split vaccination in previous seasons

BackgroundIn Navarra, Spain, subunit vaccine was first used in the 2014–2015 season, whereas trivalent split-virion influenza vaccines had been used in previous seasons. We estimate the effectiveness of the subunit vaccine in the current season and split vaccine in the two previous seasons against laboratory-confirmed influenza in the 2014–2015 season.MethodsPatients with influenza-like illness hospitalized or attended by sentinel general practitioners were swabbed for influenza testing. The previous and current vaccine status of laboratory-confirmed cases was compared to test-negative controls.ResultsAmong 1213 patients tested, 619 (51%) were confirmed for influenza virus: 52% influenza A(H3N2), 46% influenza B, and 2% A(H1N1)pdm09. The overall effectiveness for subunit vaccination in the current season was 19% (95% confidence interval [CI]: −13 to 42), 2% (95%CI: −47 to 35) against influenza A(H3N2) and 32% (95%CI: −4 to 56) against influenza B. The effectiveness against any influenza was 67% (95%CI: 17–87) for 2012–2013 and 2013–2014 vaccination only, 42% (95%CI: −31 to 74) for 2014–2015 vaccination only, and 38% (95%CI: 8–58) for vaccination in the 2012–2013, 2013–2014 and 2014–2015 seasons. The same estimates against influenza A(H3N2) were 47% (95%CI: −60 to 82), −54% (95%CI: −274 to 37) and 28% (95%CI: −17 to 56), and against influenza B were 82% (95%CI: 19–96), 93% (95%CI: 45–99) and 43% (95%CI: 5–66), respectively.ConclusionThese results suggest a considerable residual protection of split vaccination in previous seasons, low overall effectiveness of current season subunit vaccination, and possible interference between current subunit and previous split vaccines.     

Molecular epidemiology and genetic characterization of influenza B virus in Lebanon during 2016–2018

BackgroundInfluenza B viruses are a major cause of serious acute respiratory infections in humans.MethodsNasopharyngeal swabs were collected from subjects with influenza-like illness during October 2016–June 2018 and screened for influenza A and B. The hemagglutinin (HA) and neuraminidase (NA) genes of the Lebanese influenza B specimens were sequenced and phylogenetically compared with the vaccine strains and specimens from the Eastern Mediterranean Region and Europe.ResultsInfluenza A and B viruses co-circulated between October and May and peaked between January and March. During the 2016–2017 season, A/H3N2 (33.4%) and B/Yamagata (29.7%) were the predominantly circulating viruses followed by B/Victoria and A/H1N1pdm09 viruses. During the 2017–2018 season, A/H3N2 (31.5%) and A/H1Npdm09 (29.3%) were most prevalent with co-circulation of B/Yamagata and to a lesser extent B/Victoria viruses. The B/Yamagata specimens belonged to clade-3 while the B/Victoria belonged to clade-1A. None of the analyzed specimens had a mutation known to confer resistance to NA inhibitors (NAIs).ConclusionMultiple subtypes of influenza co-circulate each year in Lebanon with a peak between January and March. The trivalent vaccine included a B/Victoria strain which mismatched the B/Yamagata lineage that predominated during the study period, highlighting the importance of quadrivalent vaccines.     

Effectiveness of repeated influenza vaccination among the elderly population with high annual vaccine uptake rates during the three consecutive A/H3N2 epidemics

BackgroundAnnually, about 80% of the Korean elderly aged ≥65 years receive influenza vaccination. Repeated annual vaccination has been suggested as an important factor of poor influenza vaccine effectiveness (VE), though reported conflicting results.MethodsDuring the consecutive A/H3N2-dominant influenza seasons between 2012 and 2015, we comparatively evaluated the VE (repeated vs. current season only) against laboratory-confirmed influenza, pneumonia and hospitalization in the elderly aged ≥65 years with influenza-like illness (ILI). Clinical and demographic data were collected prospectively, and vaccination status of prior and current seasons was verified using the immunization registry data of Korean Centers for Disease Control and Prevention.ResultsDuring the first A/H3N2-dominant season in 2012–2013, influenza vaccine showed statistically significant effectiveness against influenza A infection only and when vaccinated in the current season only (VE 53%, 95% CI 15–77). In the latter two seasons (2013–2015 years), the adjusted VE for influenza A was indistinguishable between repeated vaccination and vaccination in the current season only.ConclusionDuring consecutive influenza A/H3N2 epidemics, poor influenza vaccine effectiveness may be more pronounced among the elderly population with a high annual vaccine uptake rate.     

A randomized, double-blind noninferiority study of quadrivalent live attenuated influenza vaccine in adults

Background

Trivalent seasonal influenza vaccines contain 2 A strains and 1 B strain. B strains of 2 antigenically distinct lineages, Yamagata and Victoria, have been co-circulating annually, and the B strain included in vaccines often has not been a lineage match to the major circulating strain. Thus, a vaccine containing B strains from both lineages could broaden protection against influenza. Quadrivalent live attenuated influenza vaccine (Q/LAIV) is an investigational 4-strain formulation of LAIV that contains 2 A strains, A/H1N1 and A/H3N2, and 2 B strains, 1 from each lineage.

Methods

A randomized, double-blind, active-controlled study of Q/LAIV was conducted in 1800 adults aged 18-49 years to compare the immunogenicity and safety of Q/LAIV to trivalent LAIV (T/LAIV). Subjects were randomized 4:1:1 to receive an intranasal dose of Q/LAIV (n = 1200) or 1 of 2 matching T/LAIV vaccines, each containing 1 of the B strains included in Q/LAIV (n = 600 total). The primary endpoint was the comparison of the post-vaccination strain-specific geometric mean titers (GMT) of hemagglutination inhibition antibody in Q/LAIV recipients to those in T/LAIV recipients, with immunologic noninferiority of Q/LAIV to be demonstrated if the upper bound of the 2-sided 95% confidence interval (CI) for the ratio of the GMTs [T/LAIV divided by Q/LAIV] was ≤1.5 for all strains.

Results and Conclusion

Q/LAIV met the criteria for noninferiority: the ratios of the GMTs for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 1.09 (95% CI, 1.01-1.18), 1.05 (95% CI, 0.96-1.14), 1.10 (95% CI, 0.97-1.25), and 0.92 (95% CI, 0.82-1.03), respectively. Solicited symptoms and adverse events were similar in the Q/LAIV and T/LAIV arms. Q/LAIV may confer increased protection against influenza by targeting B strains from both lineages.