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We conducted a hospital-based test-negative study in Hong Kong to estimate influenza vaccine effectiveness (VE) for the winter of 2017/18. The interim analysis included data on 1,078 children admitted between 4 December 2017 and 31 January 2018 with febrile acute respiratory illness and tested for influenza. We estimated influenza VE at 66% (95% confidence interval (CI): 43-79) overall, and 65% (95% CI: 40-80) against influenza B, the dominant virus type (predominantly B/Yamagata).

Background: The relationship between seasonal influenza vaccine and susceptibility to 2009 pandemic A/H1N1 virus infection is not fully understood., Methods: One child 6-15 years of age from each of 119 households was randomized to receive 1 dose of inactivated trivalent seasonal influenza vaccine (TIV) or saline placebo in November 2008. Serum samples were collected from study subjects and their household contacts before and 1 month after vaccination (December 2008), after winter (April 2009) and summer influenza (September-October 2009) seasons. Seasonal and pandemic influenza were confirmed by serum hemagglutinination inhibition, viral neutralization titers, and reverse-transcription polymerase chain reaction performed on nasal and throat swab samples collected during illness episodes., Results: TIV recipients had lower rates of serologically confirmed seasonal A/H1N1 infection (TIV group, 8%; placebo group, 21%; P=.10) and A/H3N2 infection (7% vs 12%; P=A9), but higher rates of pandemic A/H1N1 infection (32% vs 17%; [Formula: see text]). In multivariable analysis, those infected with seasonal influenza A during the study had a lower risk of laboratory-confirmed pandemic A/H1N1 infection (adjusted odds ratio [OR], 0.35; 95% confidence interval [CI], 0.14-0.87), and receipt of seasonal TIV was unassociated with risk of pandemic A/H1N1 infection (adjusted OR, 1.11; 95% CI, 0.54-2.26)., Conclusions: TIV protected against strain-matched infection in children. Seasonal influenza infection appeared to confer cross-protection against pandemic influenza. Whether prior seasonal influenza vaccination affects the risk of infection with the pandemic strain requires additional study., Clinical Trials Registration: ClinicalTrials.gov number NCT00792051 .

Objectives: We conducted this study to test the hypothesis that intradermal influenza vaccination at one fifth of a standard dose elicits comparable immunogenicity to full-dose intramuscular vaccination in children., Patients and Methods: We conducted a randomized, open-label study in 112 healthy children aged 3 to <18 years to compare the immunogenicity and safety of intradermal vaccination at one fifth of a dose with standard intramuscular vaccination. Analyses of hemagglutination inhibition antibody titers to each antigen in each group included geometric mean titers before and 21 days after vaccination, fold increase in geometric mean titers after vaccination, seroprotection rate, and seroconversion rate., Results: The mean age of the subjects was 10.11 +/- 4.04 years in the intradermal vaccination group and 10.57 +/- 3.91 years in the intramuscular group. Intradermal vaccination was safe. Induration and mild erythema at the injection site were reported at 25% and 57%, respectively, in the intradermal group. Fold increase of geometric mean titers against influenza A/Caledonia was robust in both groups (11.1-fold and 12.9-fold increase in the intramuscular and intradermal groups, respectively), whereas that for B/Shandong was more modest (4.3-4.4). Both approaches elicited very high geometric mean titers against influenza A/Panama: 1360.5 and 893.9 for the intramuscular and intradermal groups, respectively, but because the prevaccination antibody titers were high, the fold increase of geometric mean titers was only 4.5 and 2.6, respectively., Conclusion: The immunogenicity of one fifth of a dose of influenza vaccine delivered by the intradermal route is comparable to the standard-dose intramuscular vaccination in children as young as 3 years of age.

Influenza vaccination is an important intervention to prevent influenza virus infection. Our previous analysis suggested that indirect protection is limited in an influenza B epidemic in Hong Kong. We further analyzed six influenza A epidemics to determine such potential. We applied a statistical model to estimate household transmission dynamics in the 3 influenza A(H3N2) and 3 pandemic influenza A(H1N1) epidemics. Then, we estimated the reduction in infection risk among unvaccinated household members when all children in households are vaccinated, with different assumptions on vaccine efficacy (VE). In the optimal scenario that VE was 70%, the reduction to the total probability of infection was only marginal, with relative probabilities ranged from 0.91–0.94 when all children in households were vaccinated because community was by far the main source of infection during the six epidemics in our study. The proportion of cases attributed to household transmission was 10% (95% CrI: 7%, 13%). Individual influenza vaccination is important even when other household members are vaccinated, given the degree of indirect protection is small. [ABSTRACT FROM AUTHOR]

Background Enhanced influenza vaccines may improve protection for older adults, but comparative immunogenicity data are limited. Our objective was to examine immune responses to enhanced influenza vaccines, compared to standard-dose vaccines, in community-dwelling older adults. Methods Community-dwelling older adults aged 65–82 years in Hong Kong were randomly allocated (October 2017–January 2018) to receive 2017–2018 Northern hemisphere formulations of a standard-dose quadrivalent vaccine, MF59-adjuvanted trivalent vaccine, high-dose trivalent vaccine, or recombinant-hemagglutinin (rHA) quadrivalent vaccine. Sera collected from 200 recipients of each vaccine before and at 30-days postvaccination were assessed for antibodies to egg-propagated vaccine strains by hemagglutination inhibition (HAI) and to cell-propagated A/Hong Kong/4801/2014(H3N2) virus by microneutralization (MN). Influenza-specific CD4+ and CD8+ T cell responses were assessed in 20 participants per group. Results Mean fold rises (MFR) in HAI titers to egg-propagated A(H1N1) and A(H3N2) and the MFR in MN to cell-propagated A(H3N2) were statistically significantly higher in the enhanced vaccine groups, compared to the standard-dose vaccine. The MFR in MN to cell-propagated A(H3N2) was highest among rHA recipients (4.7), followed by high-dose (3.4) and MF59-adjuvanted (2.9) recipients, compared to standard-dose recipients (2.3). Similarly, the ratio of postvaccination MN titers among rHA recipients to cell-propagated A(H3N2) recipients was 2.57-fold higher than the standard-dose vaccine, which was statistically higher than the high-dose (1.33-fold) and MF59-adjuvanted (1.43-fold) recipient ratios. Enhanced vaccines also resulted in the boosting of T-cell responses. Conclusions In this head-to-head comparison, older adults receiving enhanced vaccines showed improved humoral and cell-mediated immune responses, compared to standard-dose vaccine recipients. Clinical Trials Registration NCT03330132. [ABSTRACT FROM AUTHOR]

Background: Two doses of influenza vaccination are recommended for previously unvaccinated children aged <9 years, and receipt of 1 dose is sometimes termed "partial vaccination." We assessed the effectiveness of partial and full influenza vaccination in preventing influenza-associated hospitalization among children in Hong Kong.Methods: Using the test-negative design we enrolled 23 187 children aged <9 years admitted to hospitals with acute respiratory illness from September 2011 through March 2019. Vaccination and influenza status were recorded. Fully vaccinated children included those vaccinated with 2 doses or, if previously vaccinated, those vaccinated with 1 dose. Partially vaccinated children included those who should have received 2 doses but only received 1 dose. We estimated vaccine effectiveness (VE) by using conditional logistic regression models matched on epidemiological week.Results: Overall VE estimates among fully and partially vaccinated children were 73% (95% confidence interval, 69%-77%) and 31% (95% confidence interval, 8%-48%), respectively. A consistently higher VE was observed in children fully vaccinated against each influenza virus type/subtype. The effectiveness of partial vaccination did not vary by age group.Conclusions: Partial vaccination was significantly less effective than full vaccination. Our study supports the current recommendation of 2 doses of influenza vaccination in previously unvaccinated children <9 years of age. [ABSTRACT FROM AUTHOR]

Background The hemagglutination inhibition (HAI) assay is an established correlate of protection for the inactivated influenza vaccine. However, the proportion of vaccine-induced protection that is mediated by the post-vaccination HAI titer has not been assessed. Methods We used data from a randomized, placebo-controlled trial of a split-virion inactivated influenza vaccine in children aged 6–17 years. Sera were collected before and 30 days after receipt of vaccination or placebo and tested by the HAI assay against B/Brisbane/60/2008-like (B/Victoria lineage). We fitted Cox proportional hazards models to the time to laboratory-confirmed influenza B. We used causal mediation analysis to estimate the proportion of the total effect of vaccination that was mediated by higher HAI titers. Results We estimated that vaccine efficacy against confirmed B/Victoria infection was 68% (95% confidence interval, 33%, 88%), and post-vaccination HAI titers explained 57% of the effect of vaccination on protection. Conclusions The majority of the effect of inactivated influenza vaccination in children is mediated by the increased HAI titer after vaccination; however, other components of the immune response to vaccination may also play a role in protection and should be further explored. Causal mediation analysis provides a framework to quantify the role of various mediators of protection. [ABSTRACT FROM AUTHOR]

Through follow-up of 796 children for up to 3 years, we found that infection with influenza A(H1N1)pdm09 in 2009–2010 and influenza A(H3N2) in 2010 was associated with protection against infection with subsequent epidemics of the same subtype.Background. School-aged children suffer high rates of influenza virus infections and associated illnesses each year, and are a major source of transmission in the community. However, information on the cumulative incidence of infection in specific epidemics is scarce, and there are limited studies with sufficient follow-up to identify the strength and duration of protection against reinfection.Methods. We randomly allocated children 5–17 years of age to receive trivalent inactivated influenza vaccine (TIV) or placebo from September 2009 through January 2010, and then conducted follow-up for 3 years including regular collection of sera, symptom diaries, and collection of nose and throat swabs during illness episodes in participants or their household members.Results. Of 796 children initially randomized, 484 continued to participate for all 3 years. In unvaccinated children, cumulative incidence of infection was estimated to be 59% in the first wave of H1N1pdm09 in 2009–2010, and 7%, 14%, 20%, and 31% in subsequent epidemics of H3N2 (2010), H1N1pdm09 (2011), B (2012), and H3N2 (2012), respectively. Infection with H1N1pdm09 in 2009–2010 and H3N2 in 2010 was associated with protection against infection with subsequent epidemics of the same subtype in 2011 and 2012, respectively, but we found no evidence of heterotypic or heterosubtypic protection against infection.Conclusions. We identified substantial incidence of influenza virus infections in children in Hong Kong in 5 major epidemics over a 3-year period, and evidence of homosubtypic but not heterosubtypic protection following infection.Clinical Trials Registration. NCT00792051. [ABSTRACT FROM PUBLISHER]

Background: There is some evidence that annual vaccination of trivalent inactivated influenza vaccine (TIV) may lead to reduced vaccine immunogenicity but evidence is lacking on whether vaccine efficacy is affected by prior vaccination history. The efficacy of one dose of TIV in children 6–8 y of age against influenza B is uncertain. We examined whether immunogenicity and efficacy of influenza vaccination in school-age children varied by age and past vaccination history. Methods and Findings: We conducted a randomized controlled trial of 2009–10 TIV. Influenza vaccination history in the two preceding years was recorded. Immunogenicity was assessed by comparison of HI titers before and one month after receipt of TIV/placebo. Subjects were followed up for 11 months with symptom diaries, and respiratory specimens were collected during acute respiratory illnesses to permit confirmation of influenza virus infections. We found that previous vaccination was associated with reduced antibody responses to TIV against seasonal A(H1N1) and A(H3N2) particularly in children 9–17 y of age, but increased antibody responses to the same lineage of influenza B virus in children 6–8 y of age. Serological responses to the influenza A vaccine viruses were high regardless of vaccination history. One dose of TIV appeared to be efficacious against confirmed influenza B in children 6–8 y of age regardless of vaccination history. Conclusions: Prior vaccination was associated with lower antibody titer rises following vaccination against seasonal influenza A vaccine viruses, but higher responses to influenza B among individuals primed with viruses from the same lineage in preceding years. In a year in which influenza B virus predominated, no impact of prior vaccination history was observed on vaccine efficacy against influenza B. The strains that circulated in the year of study did not allow us to study the effect of prior vaccination on vaccine efficacy against influenza A. [ABSTRACT FROM AUTHOR]

Background: Reliable estimates of disease burden associated with respiratory viruses are keys to deployment of preventive strategies such as vaccination and resource allocation. Such estimates are particularly needed in tropical and subtropical regions where some methods commonly used in temperate regions are not applicable. While a number of alternative approaches to assess the influenza associated disease burden have been recently reported, none of these models have been validated with virologically confirmed data. Even fewer methods have been developed for other common respiratory viruses such as respiratory syncytial virus (RSV), parainfluenza and adenovirus. Methods and Findings: We had recently conducted a prospective population-based study of virologically confirmed hospitalization for acute respiratory illnesses in persons <18 years residing in Hong Kong Island. Here we used this dataset to validate two commonly used models for estimation of influenza disease burden, namely the rate difference model and Poisson regression model, and also explored the applicability of these models to estimate the disease burden of other respiratory viruses. The Poisson regression models with different link functions all yielded estimates well correlated with the virologically confirmed influenza associated hospitalization, especially in children older than two years. The disease burden estimates for RSV, parainfluenza and adenovirus were less reliable with wide confidence intervals. The rate difference model was not applicable to RSV, parainfluenza and adenovirus and grossly underestimated the true burden of influenza associated hospitalization. Conclusion: The Poisson regression model generally produced satisfactory estimates in calculating the disease burden of respiratory viruses in a subtropical region such as Hong Kong. [ABSTRACT FROM AUTHOR]

Background. Influenza virus is a cause of substantial annual morbidity and mortality worldwide. The potential emergence of a new pandemic strain (eg, avian influenza virus) is a major concern. Currently available vaccines and anti-influenza drugs have limited effectiveness for influenza virus infections, especially for new pandemic strains. Therefore, there is an acute need to develop alternative strategies for influenza therapy. γδ T cells have potent antiviral activities against different viruses, but no data are available concerning their antiviral activity against influenza viruses. Methods. In this study, we used virus-infected primary human monocyte-derived macrophages (MDMs) to examine the antiviral activity of phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human Vγ9Vδ2 T cells against influenza viruses. Results. Vγ9Vδ2 T cells were selectively activated and expanded by IPP from peripheral blood mononuclear cells. IPP-expanded Vγ9Vδ2 T cells efficiently killed MDMs infected with human (H1N1) or avian (H9N2 or H5N1) influenza virus and significantly inhibited viral replication. The cytotoxicity of Vγ9Vδ2 T cells against influenza virus-infected MDMs was dependent on NKG2D activation and was mediated by Fas-Fas ligand and perforin-granzyme B pathways. Conclusion. Our findings suggest a potentially novel therapeutic approach to seasonal, zoonotic avian, and pandemic influenza-the use of phosphoantigens to activate γδ T cells against influenza virus infections. [ABSTRACT FROM AUTHOR]

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