Maternal Influenza Vaccination and Effect on Influenza Virus Infection in Young Infants

BACKGROUND Although pregnant women are believed to have elevated risks of severe influenza infection and are targeted for influenza vaccination, no study to date has examined influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalizations during pregnancy, primarily because this outcome poses many methodological challenges. OBJECTIVE The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) was formed in 2016 as an international collaboration with the Centers for Disease Control and Prevention; Abt Associates; and study sites in Australia, Canada, Israel, and the United States. The primary goal of this collaboration is to estimate IVE in preventing acute respiratory or febrile illness (ARFI) hospitalizations associated with laboratory-confirmed influenza virus infection during pregnancy. Secondary aims include (1) describing the incidence, clinical course, and severity of influenza-associated ARFI hospitalization during pregnancy; (2) comparing the characteristics of ARFI-hospitalized pregnant women who were tested for influenza with those who were not tested; (3) describing influenza vaccination coverage in pregnant women; and (4) comparing birth outcomes among women with laboratory-confirmed influenza-associated hospitalization versus other noninfluenza ARFI hospitalizations. METHODS For an initial assessment of IVE, sites identified a retrospective cohort of pregnant women aged from 18 to 50 years whose pregnancies overlapped with local influenza seasons from 2010 to 2016. Pregnancies were defined as those that ended in a live birth or stillbirth of at least 20 weeks gestation. The analytic sample for the primary IVE analysis was restricted to pregnant women who were hospitalized for ARFI during site-specific influenza seasons and clinically tested for influenza virus infection using real-time reverse transcription polymerase chain reaction. RESULTS We identified approximately 2 million women whose pregnancies overlapped with influenza seasons; 550,344 had at least one hospitalization during this time. After restricting to women who were hospitalized for ARFI and tested for influenza, the IVE analytic sample included 1005 women. CONCLUSIONS In addition to addressing the primary question about the effectiveness of influenza vaccination, PREVENT data will address other important knowledge gaps including understanding the incidence, clinical course, and severity of influenza-related hospitalizations during pregnancy. The data infrastructure and international partnerships created for these analyses may be useful and informative for future influenza studies. INTERNATIONAL REGISTERED REPOR DERR1-10.2196/11333

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TIV Vaccination Modulates Host Responses to Influenza Virus Infection that Correlate with Protection against Bacterial Superinfection

Vaccines ◽

10.3390/vaccines7030113 ◽

2019 ◽

Vol 7 (3) ◽

pp. 113 ◽

Cited By ~ 2

Author(s):

Choi ◽

Christopoulou ◽

Saelens ◽

García-Sastre ◽

Schotsaert

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza Vaccination ◽

Neutralizing Antibodies ◽

Influenza A ◽

Influenza Virus Infection ◽

Neutralizing Antibody ◽

Host Responses ◽

Host Immune Responses ◽

Bacterial Superinfection

Background: Influenza virus infection predisposes to secondary bacterial pneumonia. Currently licensed influenza vaccines aim at the induction of neutralizing antibodies and are less effective if the induction of neutralizing antibodies is low and/or the influenza virus changes its antigenic surface. We investigated the effect of suboptimal vaccination on the outcome of post-influenza bacterial superinfection. Methods: We established a mouse vaccination model that allows control of disease severity after influenza virus infection despite inefficient induction of virus-neutralizing antibody titers by vaccination. We investigated the effect of vaccination on virus-induced host immune responses and on the outcome of superinfection with Staphylococcus aureus. Results: Vaccination with trivalent inactivated virus vaccine (TIV) reduced morbidity after influenza A virus infection but did not prevent virus replication completely. Despite the poor induction of influenza-specific antibodies, TIV protected from mortality after bacterial superinfection. Vaccination limited loss of alveolar macrophages and reduced levels of infiltrating pulmonary monocytes after influenza virus infection. Interestingly, TIV vaccination resulted in enhanced levels of eosinophils after influenza virus infection and recruitment of neutrophils in both lungs and mediastinal lymph nodes after bacterial superinfection. Conclusion: These observations highlight the importance of disease modulation by influenza vaccination, even when suboptimal, and suggest that influenza vaccination is still beneficial to protect during bacterial superinfection in the absence of complete virus neutralization.

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Assessement of the influenza burden in nursing homes during two influenza seasons

European Journal of Public Health ◽

10.1093/eurpub/ckz187.073 ◽

2019 ◽

Vol 29 (Supplement_4) ◽

Author(s):

L Qalla-Widmer ◽

C Petignat

Keyword(s):

Influenza Virus ◽

Nursing Homes ◽

Virus Infection ◽

Influenza Vaccination ◽

Healthcare Workers ◽

Influenza Season ◽

Influenza Virus Infection ◽

Morbidity And Mortality ◽

Influenza Like Illness ◽

Vaccination Rates

Abstract Influenza is a significant cause of morbidity and mortality in elderly. They are at high risk of complications after influenza virus infection. Data on the epidemiology of influenza within nursing homes (NH) are limited. The purpose of this prospective study was to better describe the burden of influenza among residents of NH of canton of Vaud, Switzerland, with influenza-like illness during 2016-2017 and 2017-2018 influenza seasons. First, we determined the proportion of influenza-like illness due to influenza in NH residents. We specifically assessed the impact of a positive influenza PCR on clinical features, morbidity and mortality, 30 and 90 days after diagnosis, as compared to a negative influenza PCR. Moreover, influenza vaccination rates of the residents and the healthcare workers within each nursing home were assessed at the end of each influenza season. A PCR test was performed on 509 residents from 61 NH. 227 influenza virus infections were diagnosed; 181 influenza A and 46 influenza B. Compared to residents without influenza virus infection (IVI), residents with IVI were more often feverish with a high fever (69.1% and 88.5% respectively, p < 0.0001) are significantly more frequently hospitalized within 30 days after diagnosis (17.6% vs 7.1%, p = 0.0003). Any cause mortality at 30 days was similar in both groups (12.8% vs 10.6%, p = 0.48). Only 18.1% of IVI residents were treated with an antiviral and 60.4% of them received antibiotics. Influenza vaccination rates of the healthcare workers and residents were respectively 50% and 82%. During influenza season, the feverish residents should be suspected to have influenza virus infection. Residents should be diagnosed (PCR) and treated with an antiviral where appropriate to limit the risk of hospitalization. Healthcare workers should be encouraged to be vaccinated against influenza in order to acquire a better herd immunity within the NH which will limit the spread of influenza. Key messages Influenza virus in nursing homes is not treated enough. Influenza virus infection in nursing homes causes a high number of hospitalizations.

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Distinct Patterns of B-Cell Activation and Priming by Natural Influenza Virus Infection Versus Inactivated Influenza Vaccination

The Journal of Infectious Diseases ◽

10.1093/infdis/jiu580 ◽

2014 ◽

Vol 211 (7) ◽

pp. 1051-1059 ◽

Cited By ~ 18

Author(s):

Xiao-Song He ◽

Tyson H. Holmes ◽

Mrinmoy Sanyal ◽

Randy A. Albrecht ◽

Adolfo García-Sastre ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza Vaccination ◽

B Cell ◽

Cell Activation ◽

Influenza Virus Infection ◽

B Cell Activation

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Inclusion of Flagellin during Vaccination against Influenza Enhances Recall Responses in Nonhuman Primate Neonates

Journal of Virology ◽

10.1128/jvi.00549-15 ◽

2015 ◽

Vol 89 (14) ◽

pp. 7291-7303 ◽

Cited By ~ 24

Author(s):

Jong R. Kim ◽

Beth C. Holbrook ◽

Sarah L. Hayward ◽

Lance K. Blevins ◽

Matthew J. Jorgensen ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Nonhuman Primate ◽

Severe Disease ◽

Influenza Virus Infection ◽

Vulnerable Population ◽

Primate Model ◽

Vaccine Responses ◽

Young Infants ◽

Toll Like Receptor 5

ABSTRACTInfluenza virus can cause life-threatening infections in neonates and young infants. Although vaccination is a major countermeasure against influenza, current vaccines are not approved for use in infants less than 6 months of age, in part due to the weak immune response following vaccination. Thus, there is a strong need to develop new vaccines with improved efficacy for this vulnerable population. To address this issue, we established a neonatal African green monkey (AGM) nonhuman primate model that could be used to identify effective influenza vaccine approaches for use in young infants. We assessed the ability of flagellin, a Toll-like receptor 5 (TLR5) agonist, to serve as an effective adjuvant in this at-risk population. Four- to 6-day-old AGMs were primed and boosted with inactivated PR8 influenza virus (IPR8) adjuvanted with either wild-type flagellin or inactive flagellin with a mutation at position 229 (m229), the latter of which is incapable of signaling through TLR5. Increased IgG responses were observed following a boost, as well as at early times after challenge, in infants vaccinated with flagellin-adjuvanted IPR8. Inclusion of flagellin during vaccination also resulted in a significantly increased number of influenza virus-specific T cells following challenge compared to the number in infants vaccinated with the m229 adjuvant. Finally, following challenge infants vaccinated with IPR8 plus flagellin exhibited a reduced pathology in the lungs compared to that in infants that received IPR8 plus m229. This study provides the first evidence of flagellin-mediated enhancement of vaccine responses in nonhuman primate neonates.IMPORTANCEYoung infants are particularly susceptible to severe disease as a result of influenza virus infection. Compounding this is the lack of effective vaccines for use in this vulnerable population. Here we describe a vaccine approach that results in improved immune responses and protection in young infants. Incorporation of flagellin during vaccination resulted in increased antibody and T cell responses together with reduced disease following virus infection. These results suggest that flagellin may serve as an effective adjuvant for vaccines targeted to this vulnerable population.

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Influenza vaccine effectiveness in reducing severe outcomes over six influenza seasons, a case-case analysis, Spain, 2010/11 to 2015/16

Eurosurveillance ◽

10.2807/1560-7917.es.2018.23.43.1700732 ◽

2018 ◽

Vol 23 (43) ◽

Cited By ~ 10

Author(s):

Pere Godoy ◽

Arantxa Romero ◽

Núria Soldevila ◽

Nuria Torner ◽

Mireia Jané ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza Vaccination ◽

Antiviral Treatment ◽

Age Groups ◽

Influenza Virus Infection ◽

Vaccination Uptake ◽

Icu Admission ◽

Hospitalised Patients ◽

Positive Effect

Introduction When influenza vaccination is ineffective in preventing influenza virus infection, it may still reduce the severity of influenza-associated disease. Here, we estimate the effect of influenza vaccination in preventing severe outcomes e.g. intensive care unit (ICU) admission and death, even though it did not prevent influenza virus infection and subsequent hospitalisation. Methods An observational case–case epidemiological study was carried out in 12 sentinel hospitals in Catalonia (Spain) over six influenza seasons 2010/11–2015/16. Cases were individuals with severe laboratory-confirmed influenza virus infection and aged 18 years and older. For each reported case we collected demographic, virological and clinical characteristics. Logistic regression was used to estimate the crude, adjusted odd ratios (aOR) and 95% confidence intervals (CI). Results Of 1,727 hospitalised patients included in the study, 799 were female (46.7%), 591 (34.2%) were admitted to the ICU and 223 (12.9%) died. Influenza vaccination uptake was lower in cases that required ICU admission or died (21.2% vs 29.7%, p < 0.001). The adjusted influenza vaccination effectiveness in preventing ICU admission or death was 23% (95% CI: 1 to 40). In an analysis restricted to sex, age group and antiviral treatment, influenza vaccination had a positive effect on disease severity in all age groups and categories. Conclusions We found that influenza vaccination reduced the severity of disease even in cases where it did not prevent infection and influenza-associated hospitalisation. Therefore, increased vaccination uptake may reduce complications, ICU admission and death.

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Protective Efficacy of Seasonal Influenza Vaccination against Seasonal and Pandemic Influenza Virus Infection during 2009 in Hong Kong

Clinical Infectious Diseases ◽

10.1086/657311 ◽

2010 ◽

Vol 51 (12) ◽

pp. 1370-1379 ◽

Cited By ~ 111

Author(s):

Benjamin J. Cowling ◽

Sophia Ng ◽

Edward S. K. Ma ◽

Calvin K. Y. Cheng ◽

Winnie Wai ◽

...

Keyword(s):

Influenza Virus ◽

Hong Kong ◽

Virus Infection ◽

Influenza Vaccination ◽

Pandemic Influenza ◽

Seasonal Influenza ◽

Protective Efficacy ◽

Influenza Virus Infection ◽

Seasonal Influenza Vaccination

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Assay Harmonization and Use of Biological Standards To Improve the Reproducibility of the Hemagglutination Inhibition Assay: a FLUCOP Collaborative Study

mSphere ◽

10.1128/msphere.00567-21 ◽

2021 ◽

Author(s):

Joanna Waldock ◽

Lingyi Zheng ◽

Edmond J. Remarque ◽

Alexandre Civet ◽

Branda Hu ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Influenza Vaccination ◽

Hemagglutination Inhibition ◽

Collaborative Study ◽

Influenza Virus Infection ◽

Inhibition Assay ◽

Hemagglutination Inhibition Assay ◽

Standardization Of Procedures ◽

Meaningful Data

The hemagglutination inhibition (HAI) assay is the most commonly used serology assay to detect antibodies from influenza vaccination or influenza virus infection. This assay has been used for decades but requires improved standardization of procedures to provide meaningful data.

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