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Data on the immunologic responses to neuraminidase (NA) is lacking compared to what is available on hemagglutinin (HA) responses, despite growing evidence that NA immunity can be protective and broadly cross-reactive. Understanding these NA responses during natural infection is key to exploiting these properties for improving influenza vaccines. Using two community-acquired influenza cohorts, we showed that the induction of both HA and NA antibodies after infection is influenced by age and subtypes. Such response dynamics suggest the influence of immunological memory, and understanding how this process is regulated will be critical to any vaccine effort targeting NA immunity., Despite evidence that antibodies targeting the influenza virus neuraminidase (NA) protein can be protective and are broadly cross-reactive, the immune response to NA during infection is poorly understood compared to the response to hemagglutinin (HA) protein. As such, we compared the antibody profile to HA and NA in two naturally infected human cohorts in Auckland, New Zealand: (i) a serosurvey cohort, consisting of pre- and post-influenza season sera from PCR-confirmed influenza cases (n = 50), and (ii) an immunology cohort, consisting of paired sera collected after PCR-confirmation of infection (n = 94). The induction of both HA and NA antibodies in these cohorts was influenced by age and subtype. Seroconversion to HA was more frequent in those

We investigated risk factors for severe acute lower respiratory infections (ALRI) among hospitalised children 8 months were at greater risk from influenza-associated ICU admissions and long hospital stay. Children with ADV had increased LOS across all ages. In the first 2 years of life, the effects of different viruses on ALRI severity varies with age. Our findings help to identify specific ages that would most benefit from virus-specific interventions such as vaccines and antivirals.

Background. The immunologic factors underlying severe influenza are poorly understood. To address this, we compared the immune responses of influenza-confirmed hospitalized individuals with severe acute respiratory illness (SARI) to those of nonhospitalized individuals with influenza-like illness (ILI).Methods. Peripheral blood lymphocytes were collected from 27 patients with ILI and 27 with SARI, at time of enrollment and then 2 weeks later. Innate and adaptive cellular immune responses were assessed by flow cytometry, and serum cytokine levels were assessed by a bead-based assay. Results. During the acute phase, SARI was associated with significantly reduced numbers of circulating myeloid dendritic cells, CD192+ monocytes, and influenza virus–specific CD8+ and CD4+ T cells as compared to ILI. By the convalescent phase, however, most SARI cases displayed continued immune activation characterized by increased numbers of CD16+ monocytes and proliferating, and influenza virus–specific, CD8+ T cells as compared to ILI cases. SARI was also associated with reduced amounts of cytokines that regulate T-cell responses (ie, interleukin 4, interleukin 13, interleukin 12, interleukin 10, and tumor necrosis factor β) and hematopoiesis (interleukin 3 and granulocyte-macrophage colony-stimulating factor) but increased amounts of a proinflammatory cytokine (tumor necrosis factor α), chemotactic cytokines (MDC, MCP-1, GRO, and fractalkine), and growth-promoting cytokines (PDGFBB/AA, VEGF, and EGF) as compared to ILI.Conclusions. Severe influenza cases showed a delay in the peripheral immune activation that likely led prolonged inflammation, compared with mild influenza cases.

Background Understanding the attack rate of influenza infection and the proportion who become ill by risk group is key to implementing prevention measures. While population-based studies of antihemagglutinin antibody responses have been described previously, studies examining both antihemagglutinin and antineuraminidase antibodies are lacking. Methods In 2015, we conducted a seroepidemiologic cohort study of individuals randomly selected from a population in New Zealand. We tested paired sera for hemagglutination inhibition (HAI) or neuraminidase inhibition (NAI) titers for seroconversion. We followed participants weekly and performed influenza polymerase chain reaction (PCR) for those reporting influenza-like illness (ILI). Results Influenza infection (either HAI or NAI seroconversion) was found in 321 (35% [95% confidence interval, 32%-38%]) of 911 unvaccinated participants, of whom 100 (31%) seroconverted to NAI alone. Young children and Pacific peoples experienced the highest influenza infection attack rates, but overall only a quarter of all infected reported influenza PCR-confirmed ILI, and one-quarter of these sought medical attention. Seroconversion to NAI alone was higher among children aged

Little is known about inactivated influenza vaccine effectiveness (IVE) in preventing very severe disease, including influenza-associated intensive care unit (ICU) admissions.The Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) project enrolled adults (aged ≥ 18 years) with acute respiratory illness (ARI) in general ward (GW) hospital settings (n = 3034) and ICUs (n = 101) during 2012-2015. IVE was assessed using a test-negative design comparing the odds of influenza vaccination among influenza positives vs. negatives (confirmed by real-time reverse transcription polymerase chain reaction). All models were adjusted for season, weeks from season peak, and a vaccination propensity score.Influenza virus infection was confirmed in 28% of GW hospital and 41% of ICU patients; influenza vaccination was documented for 56% and 41%, respectively. Across seasons, IVE was 37% (95% confidence intervals [CI] = 23-48%) among GW patients and 82% (95% CI = 45-94%) among ICU patients. IVE point estimates were 70% against ICU influenza and consistently higher than IVE against GW influenza when stratified by season, by virus (sub)types, and for adults with or without chronic medical conditions and for both adults aged65 and ≥65 years old. Among hospitalized influenza positives, influenza vaccination was associated with a 59% reduction in the odds of ICU admission (aOR = 0.41, 95% CI = 0.18-0.96) and with shorter ICU lengths of stay (LOS), but not with radiograph-confirmed pneumonia or GW hospital LOS.Inactivated influenza vaccines prevented influenza-associated ICU admissions, may have higher effectiveness in ICU than GW hospital settings, and appeared to reduce the risk of severe disease among those who are infected despite vaccination.

We present preliminary results of influenza vaccine effectiveness (VE) in New Zealand using a case test-negative design for 28 April to 31 August 2014. VE adjusted for age and time of admission among all ages against severe acute respiratory illness hospital presentation due to laboratory-confirmed influenza was 54% (95% CI: 19 to 74) and specifically against A(H1N1)pdm09 was 65% (95% CI:33 to 81). For influenza-confirmed primary care visits, VE was 67% (95% CI: 48 to 79) overall and 73% (95% CI: 50 to 85) against A(H1N1)pdm09.