Low 2018/19 vaccine effectiveness against influenza A(H3N2) among 15–64-year-olds in Europe: exploration by birth cohort

Introduction Influenza A(H3N2) clades 3C.2a and 3C.3a co-circulated in Europe in 2018/19. Immunological imprinting by first childhood influenza infection may induce future birth cohort differences in vaccine effectiveness (VE). Aim The I-MOVE multicentre primary care test-negative study assessed 2018/19 influenza A(H3N2) VE by age and genetic subgroups to explore VE by birth cohort. Methods We measured VE against influenza A(H3N2) and (sub)clades. We stratified VE by usual age groups (0–14, 15–64, ≥ 65-years). To assess the imprint-regulated effect of vaccine (I-REV) hypothesis, we further stratified the middle-aged group, notably including 32–54-year-olds (1964–86) sharing potential childhood imprinting to serine at haemagglutinin position 159. Results Influenza A(H3N2) VE among all ages was −1% (95% confidence interval (CI): −24 to 18) and 46% (95% CI: 8–68), −26% (95% CI: −66 to 4) and 20% (95% CI: −20 to 46) among 0–14, 15–64 and ≥ 65-year-olds, respectively. Among 15–64-year-olds, VE against clades 3C.2a1b and 3C.3a was 15% (95% CI: −34 to 50) and −74% (95% CI: −259 to 16), respectively. VE was −18% (95% CI: −140 to 41), −53% (95% CI: −131 to −2) and −12% (95% CI: −74 to 28) among 15–31-year-olds (1987–2003), 32–54-year-olds (1964–86) and 55–64-year-olds (1954–63), respectively. Discussion The lowest 2018/19 influenza A(H3N2) VE was against clade 3C.3a and among those born 1964–86, corresponding to the I-REV hypothesis. The low influenza A(H3N2) VE in 15–64-year-olds and the public health impact of the I-REV hypothesis warrant further study.

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Birth Cohort Effects in Influenza Surveillance Data: Evidence That First Influenza Infection Affects Later Influenza-Associated Illness

The Journal of Infectious Diseases ◽

10.1093/infdis/jiz201 ◽

2019 ◽

Vol 220 (5) ◽

pp. 820-829 ◽

Cited By ~ 16

Author(s):

Alicia P Budd ◽

Lauren Beacham ◽

Catherine B Smith ◽

Rebecca J Garten ◽

Carrie Reed ◽

...

Keyword(s):

Influenza Virus ◽

Birth Cohort ◽

Influenza A ◽

Influenza Infection ◽

Surveillance Data ◽

Influenza Surveillance ◽

Severe Illness ◽

Birth Cohorts ◽

Influenza A Viruses ◽

Cohort Differences

Abstract Background The evolution of influenza A viruses results in birth cohorts that have different initial influenza virus exposures. Historically, A/H3 predominant seasons have been associated with more severe influenza-associated disease; however, since the 2009 pandemic, there are suggestions that some birth cohorts experience more severe illness in A/H1 predominant seasons. Methods United States influenza virologic, hospitalization, and mortality surveillance data during 2000–2017 were analyzed for cohorts born between 1918 and 1989 that likely had different initial influenza virus exposures based on viruses circulating during early childhood. Relative risk/rate during H3 compared with H1 predominant seasons during prepandemic versus pandemic and later periods were calculated for each cohort. Results During the prepandemic period, all cohorts had more influenza-associated disease during H3 predominant seasons than H1 predominant seasons. During the pandemic and later period, 4 cohorts had higher hospitalization and mortality rates during H1 predominant seasons than H3 predominant seasons. Conclusions Birth cohort differences in risk of influenza-associated disease by influenza A virus subtype can be seen in US influenza surveillance data and differ between prepandemic and pandemic and later periods. As the population ages, the amount of influenza-associated disease may be greater in future H1 predominant seasons than H3 predominant seasons.

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Paradoxical clade- and age-specific vaccine effectiveness during the 2018/19 influenza A(H3N2) epidemic in Canada: potential imprint-regulated effect of vaccine (I-REV)

Eurosurveillance ◽

10.2807/1560-7917.es.2019.24.46.1900585 ◽

2019 ◽

Vol 24 (46) ◽

Cited By ~ 12

Author(s):

Danuta M Skowronski ◽

Suzana Sabaiduc ◽

Siobhan Leir ◽

Caren Rose ◽

Macy Zou ◽

...

Keyword(s):

Amino Acid ◽

Influenza A ◽

Influenza Infection ◽

Cohort Effect ◽

Vaccine Effectiveness ◽

Age Group ◽

Surveillance Network ◽

Amino Acid Variation ◽

Immunological Mechanisms

Introduction The Canadian Sentinel Practitioner Surveillance Network reports vaccine effectiveness (VE) for the 2018/19 influenza A(H3N2) epidemic. Aim To explain a paradoxical signal of increased clade 3C.3a risk among 35–54-year-old vaccinees, we hypothesise childhood immunological imprinting and a cohort effect following the 1968 influenza A(H3N2) pandemic. Methods We assessed VE by test-negative design for influenza A(H3N2) overall and for co-circulating clades 3C.2a1b and 3C.3a. VE variation by age in 2018/19 was compared with amino acid variation in the haemagglutinin glycoprotein by year since 1968. Results Influenza A(H3N2) VE was 17% (95% CI: −13 to 39) overall: 27% (95% CI: −7 to 50) for 3C.2a1b and −32% (95% CI: −119 to 21) for 3C.3a. Among 20–64-year-olds, VE was −7% (95% CI: −56 to 26): 6% (95% CI: −49 to 41) for 3C.2a1b and −96% (95% CI: −277 to −2) for 3C.3a. Clade 3C.3a VE showed a pronounced negative dip among 35–54-year-olds in whom the odds of medically attended illness were > 4-fold increased for vaccinated vs unvaccinated participants (p < 0.005). This age group was primed in childhood to influenza A(H3N2) viruses that for two decades following the 1968 pandemic bore a serine at haemagglutinin position 159, in common with contemporary 3C.3a viruses but mismatched to 3C.2a vaccine strains instead bearing tyrosine. Discussion Imprinting by the first childhood influenza infection is known to confer long-lasting immunity focused toward priming epitopes. Our findings suggest vaccine mismatch may negatively interact with imprinted immunity. The immunological mechanisms for imprint-regulated effect of vaccine (I-REV) warrant investigation.

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Improved Cognitive Function in the Tromsø Study in Norway From 2001 to 2016

Neurology Clinical Practice ◽

10.1212/cpj.0000000000001115 ◽

2021 ◽

pp. 10.1212/CPJ.0000000000001115

Author(s):

Bente Johnsen ◽

Bjørn Heine Strand ◽

Ieva Martinaityte ◽

Ellisiv B. Mathiesen ◽

Henrik Schirmer

Keyword(s):

Physical Activity ◽

Birth Cohort ◽

Age Groups ◽

Cohort Effect ◽

Cognitive Test ◽

Birth Cohorts ◽

Cohort Differences ◽

Level Increase ◽

Drinking Frequency ◽

Birth Cohort Effect

AbstractObjective:Physical capacity and cardiovascular risk profiles seem to be improving in the population. Cognition have been improving due to a birth cohort effect, but evidence is conflicting on whether this improvement remains in the latest decades, and what is causing the changes in our population over 60 years old. We aimed to investigate birth cohort differences in cognition.Method:The study comprised 9514 participants from the Tromsø study, an ongoing longitudinal cohort study. Participants were in the ages 60–87 years, born between 1914 and 1956. They did four cognitive tests in three waves during 2001-2016. Linear regression was applied, and adjusted for age, education, blood pressure, smoking, hypercholesterolemia, stroke, heart attack, depression, diabetes, physical activity, alcohol use, BMI and height.Results:Cognitive test scores were better in later-born birth cohorts for all age groups, and in both sexes, compared with earlier born cohorts. Increased education, physical activity, alcohol intake, decreasing smoking prevalence and increasing height was associated with one third of this improvement across birth cohorts in women and one half of the improvement in men.Conclusion:Cognitive results were better in more recent born birth cohorts compared with earlier born, assessed at the same age. The improvement was present in all cognitive domains, suggesting an overall improvement in cognitive performance. The 80-year-olds assessed in 2015-16 performed like 60-year-olds assessed in 2001. The improved scores were associated with increased education level, increase in modest drinking frequency, increased physical activity and for men, smoking cessation and increased height.

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How can the public health impact of vaccination be estimated?

BMC Public Health ◽

10.1186/s12889-021-12040-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Susy Echeverria-Londono ◽

Xiang Li ◽

Jaspreet Toor ◽

Margaret J. de Villiers ◽

Shevanthi Nayagam ◽

...

Keyword(s):

Birth Cohort ◽

Health Impact ◽

Activity Type ◽

Yearly Variation ◽

Vaccine Preventable Diseases ◽

The Public ◽

Full Effect ◽

Impact Modelling ◽

Vaccine Impact ◽

The Impact

Abstract Background Deaths due to vaccine preventable diseases cause a notable proportion of mortality worldwide. To quantify the importance of vaccination, it is necessary to estimate the burden averted through vaccination. The Vaccine Impact Modelling Consortium (VIMC) was established to estimate the health impact of vaccination. Methods We describe the methods implemented by the VIMC to estimate impact by calendar year, birth year and year of vaccination (YoV). The calendar and birth year methods estimate impact in a particular year and over the lifetime of a particular birth cohort, respectively. The YoV method estimates the impact of a particular year’s vaccination activities through the use of impact ratios which have no stratification and stratification by activity type and/or birth cohort. Furthermore, we detail an impact extrapolation (IE) method for use between coverage scenarios. We compare the methods, focusing on YoV for hepatitis B, measles and yellow fever. Results We find that the YoV methods estimate similar impact with routine vaccinations but have greater yearly variation when campaigns occur with the birth cohort stratification. The IE performs well for the YoV methods, providing a time-efficient mechanism for updates to impact estimates. Conclusions These methods provide a robust set of approaches to quantify vaccination impact; however it is vital that the area of impact estimation continues to develop in order to capture the full effect of immunisation.

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Pandemic influenza A(H1N1) 2009 breakthrough infections and estimates of vaccine effectiveness in Germany 2009-2010

Eurosurveillance ◽

10.2807/ese.15.18.19561-en ◽

2010 ◽

Vol 15 (18) ◽

Author(s):

O Wichmann ◽

P Stöcker ◽

G Poggensee ◽

D Altmann ◽

D Walter ◽

...

Keyword(s):

Pandemic Influenza ◽

Influenza A ◽

Influenza Pandemic ◽

Rapid Assessment ◽

Screening Method ◽

Age Groups ◽

Vaccine Effectiveness ◽

Influenza A H1n1 ◽

Reported Data ◽

2009 Influenza Pandemic

During the 2009 influenza pandemic, a monovalent AS03-adjuvanted vaccine was almost exclusively used in Germany for immunisation against the 2009 pandemic influenza A(H1N1) virus. One-dose vaccination was recommended for all age groups. We applied the screening method for the rapid assessment of vaccine effectiveness (VE) based on reported data of vaccinated and unvaccinated pandemic influenza cases and vaccination coverage estimates. Preliminary results demonstrate excellent VE in persons aged 14-59 years (96.8%; 95% confidence interval (CI): 95.2-97.9) and moderately high VE in those 60 years or older (83.3%; 95% CI: 71.0-90.5).

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Impact of Influenza on Pneumococcal Vaccine Effectiveness during Streptococcus pneumoniae Infection in Aged Murine Lung

Vaccines ◽

10.3390/vaccines8020298 ◽

2020 ◽

Vol 8 (2) ◽

pp. 298

Author(s):

Ermias Jirru ◽

Stefi Lee ◽

Rebecca Harris ◽

Jianjun Yang ◽

Soo Jung Cho ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Immune Responses ◽

Pneumococcal Vaccine ◽

Influenza A ◽

Secondary Infection ◽

Influenza Infection ◽

Vaccine Effectiveness ◽

Murine Lung ◽

Vaccine Responses ◽

Secondary Infections

Changes in innate and adaptive immune responses caused by viral imprinting can have a significant direct or indirect influence on secondary infections and vaccine responses. The purpose of our current study was to investigate the role of immune imprinting by influenza on pneumococcal vaccine effectiveness during Streptococcus pneumoniae infection in the aged murine lung. Aged adult (18 months) mice were vaccinated with the pneumococcal polyvalent vaccine Pneumovax (5 mg/mouse). Fourteen days post vaccination, mice were instilled with PBS or influenza A/PR8/34 virus (3.5 × 102 PFU). Control and influenza-infected mice were instilled with PBS or S. pneumoniae (1 × 103 CFU, ATCC 6303) on day 7 of infection and antibacterial immune responses were assessed in the lung. Our results illustrate that, in response to a primary influenza infection, there was diminished bacterial clearance and heightened production of pro-inflammatory cytokines, such as IL6 and IL1β. Vaccination with Pneumovax decreased pro-inflammatory cytokine production by modulating NFҡB expression; however, these responses were significantly diminished after influenza infection. Taken together, the data in our current study illustrate that immune imprinting by influenza diminishes pneumococcal vaccine efficacy and, thereby, may contribute to increased susceptibility of older persons to a secondary infection with S. pneumoniae.

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Effectiveness of influenza vaccination in preventing hospitalisation due to influenza in children: a systematic review and meta-analysis

Clinical Infectious Diseases ◽

10.1093/cid/ciab270 ◽

2021 ◽

Author(s):

Nicki L Boddington ◽

Isabelle Pearson ◽

Heather Whitaker ◽

Punam Mangtani ◽

Richard G Pebody

Keyword(s):

Systematic Review ◽

Influenza Vaccine ◽

Influenza Vaccination ◽

Random Effects ◽

Influenza A ◽

Influenza Infection ◽

Meta Analysis ◽

Vaccine Effectiveness ◽

Vaccine Type ◽

Inactivated Vaccines

Abstract This systematic review assesses the literature for estimates of influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalisation in children. Studies of any design to 08 June 2020 were included if the outcome was hospitalisation, participants were 17 years old or less and influenza infection was laboratory-confirmed. A random-effects meta-analysis of 37 studies that used a test-negative design gave a pooled seasonal IVE against hospitalisation of 53.3% (47.2-58.8) for any influenza. IVE was higher against influenza A/H1N1pdm09 (68.7%, 56.9-77.2) and lowest against influenza A/H3N2 (35.8%, 23.4-46.3). Estimates by vaccine type ranged from 44.3% (30.1-55.7) for LAIV to 68.9% (53.6-79.2) for inactivated vaccines. IVE estimates were higher in seasons when the circulating influenza strains were antigenically matched to vaccine strains (59.3%, 48.3-68.0). Influenza vaccination gives moderate overall protection against influenza-associated hospitalisation in children supporting annual vaccination. IVE varies by influenza subtype and vaccine type.

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Age-specific differences in the dynamics of protective immunity to influenza

10.1101/330720 ◽

2018 ◽

Cited By ~ 2

Author(s):

Sylvia Ranjeva ◽

Rahul Subramanian ◽

Vicky J. Fang ◽

Gabriel M. Leung ◽

Dennis K. M. Ip ◽

...

Keyword(s):

Protective Immunity ◽

Influenza A ◽

Influenza Infection ◽

Age Groups ◽

Virus Infections ◽

Influenza A Viruses ◽

Individual Level ◽

Antibody Titers ◽

Original Antigenic Sin ◽

Changes Over Time

AbstractInfluenza A viruses evolve rapidly to escape host immunity, such that individuals can be infected multiple times with the same subtype. The form and duration of protective immunity after each influenza infection are poorly understood. Here, we quantify the dynamics of protective immunity against influenza A virus infections by fitting individual-level mechanistic models to longitudinal serology from children and adults in a household cohort study. We find that most protection in children is explained by antibody titers measured by the hemagglutination inhibition (HI) assay. In contrast, in adults, HI antibody titers explain a smaller fraction of protection. Protection against circulating strains wanes to approximately 50% of peak levels 3.5-7 years after infection in both age groups, and wanes faster against influenza A(H3N2) than A(H1N1)pdm09. Protection against H3N2 lasts longer in adults than in children. Our results suggest that the focus of influenza antibody responses changes over time from the highly mutable hemagglutinin head to other epitopes, consistent with the immunological theory of original antigenic sin, and that this change of focus might affect protection. Additionally, we estimate that imprinting, or primary infection with a subtype of one phylogenetic group, has little to no effect on the risk of non-medically attended influenza infections in adults. We also find no evidence of long-term cross-protection between subtypes. This work underscores the need for longitudinal data on multiple components of the immune response to better understand the development of immunity and differences in susceptibility within populations.

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Immunoglobulin G, A and M response to influenza vaccination in different age groups: effects of priming and boosting

Journal of Hygiene ◽

10.1017/s0022172400066316 ◽

1986 ◽

Vol 96 (3) ◽

pp. 513-522 ◽

Cited By ~ 12

Author(s):

Walter E. P. Beyer ◽

Jos T. M. Van Der Logt ◽

Ruud van Beek ◽

Nic Masurel

Keyword(s):

Antibody Response ◽

Influenza Vaccine ◽

Influenza A ◽

Influenza Infection ◽

Age Groups ◽

Antibody Responses ◽

Trivalent Influenza Vaccine ◽

Antibody Capture ◽

The Mean ◽

Original Antigenic Sin

SUMMARYFifty volunteers, treated with an inactivated trivalent influenza vaccine containing A/Bangkok/1/79 (H3N2), A/Brazil/11/78 (H1N1) and B/Singapore/222/79 virus, were subdivided according to the estimated first exposure to influenza in their lifetime (priming) and the presence of antibodies against the vaccine components in the pre-vaccination sera. The isotypic antibody response (IgG, IgA, IgM) was determined by means of an antibody capture haemadsorption immunosorbent technique. For all three vaccine components, previously seropositive subjects produced antibodies of the IgG- and IgA-class more frequently than previously seronegative persons. Subjects primed to one of the influenza A subtypes showed more IgG and IgA responses in comparison with those unprimed (prime-effect). In contrast, IgM antibodies occurred in only 19 and 11% of primed, but in 59 and 54% of unprimed subjects, for A (H3N2) and A (HlNl), respectively. The incidence of IgM titre rises was not influenced by the prevaccination state. However, the mean magnitude of anti-A(H1N1)-IgM titre rises was greater in those previously seronegative. The concepts of primary and reinfection and of ‘original antigenic sin’ are discussed, and it is suggested that age and, if possible, serological state prior to antigen-exposure should be taken into account when studying isotypic antibody responses after influenza infection or vaccination.

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Early lessons from schistosomiasis mass drug administration programs

F1000Research ◽

10.12688/f1000research.6826.1 ◽

2015 ◽

Vol 4 ◽

pp. 1157 ◽

Cited By ~ 11

Author(s):

W. Evan Secor

Keyword(s):

Drug Administration ◽

Mass Drug Administration ◽

Age Groups ◽

Health Impact ◽

Diagnostic Tools ◽

Practical Application ◽

Schistosomiasis Control ◽

The Public ◽

Control Programs ◽

Morbidity Control

Mass drug administration using praziquantel is the backbone of the current strategy for the control of schistosomiasis. As the theoretical plans have moved into practical application, certain challenges with this approach have surfaced, and it is likely that annual mass drug administration alone may not be sufficient to achieve program goals. However, mass drug administration is still the only available intervention that can be readily used in the wide variety of settings where schistosomiasis is endemic. The task then becomes how to improve this approach and identify what adjuncts to mass drug administration are effective, as programs move from morbidity control to elimination goals. Other aspects worthy of consideration include how best to employ new diagnostic tools to more easily identify where treatment is needed, and new formulations of praziquantel to extend the availability of treatment to all age groups. The aim of this review is to highlight both areas of challenge and of opportunity to improve the public health impact of schistosomiasis control programs.

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