Delayed Supply of Influenza Vaccine and Adjunct ACIP Influenza Vaccine Recommendations for the 2000-01 Influenza Season

Abstract Background In recent studies of influenza vaccine effectiveness (VE), lower effectiveness with increasing time since vaccination was observed, raising the question of optimal vaccination timing. We sought to evaluate the estimated number of influenza-associated hospitalizations among older adults due to potential changes in vaccination timing. Methods Using empirical data and a health state transition model, we estimated change in influenza-associated hospitalizations predicted to occur among the US population aged ≥65 years if vaccination were delayed until October 1. We assumed the vaccination timing, coverage, and effectiveness observed in 2012–2013 as a prototypical influenza season, approximately 7% monthly waning of VE, and that between 0% and 50% of individuals who usually get vaccinated earlier than October failed to get vaccinated. We also assessed change in influenza-associated hospitalizations if vaccination uptake shifted substantially toward August and September. Results In a typical season, delaying vaccination until October increased influenza hospitalizations if more than 14% of older adults usually vaccinated in August and September failed to get vaccinated. The consequences of delayed vaccination depended heavily on influenza season timing, rate of waning, and overall VE. A shift toward vaccination in August and September led to, on average, an increase in influenza-associated hospitalizations, but this result was also sensitive to influenza season timing. Conclusions Consequences of delayed vaccination varied widely. Uncertainties about vaccine waning and effects of a delay on vaccine coverage suggest it is premature to change current vaccine recommendations, although it may be prudent to prevent a substantial shift toward early vaccination.

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22. Description of Hospitalized Patients with Influenza Vaccine Failure

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.067 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S35-S35

Author(s):

Joanna Kimball ◽

Yuwei Zhu ◽

Dayna Wyatt ◽

Helen Talbot

Keyword(s):

Logistic Regression ◽

Influenza Vaccine ◽

Influenza Vaccination ◽

Older Patients ◽

Influenza A ◽

Influenza Season ◽

Hospitalized Patients ◽

Vaccine Failure ◽

Increased Risk ◽

Immunosuppressed Patients

Abstract Background Despite influenza vaccination, some patients develop illness and require hospitalization. Many factors contribute to vaccine failure, including mismatch of the vaccine and circulating strains, waning immunity, timing of influenza season, age and patient comorbidities such as immune function. This study compared vaccinated, hospitalized patients with and without influenza. Methods This study used 2015–2019 Tennessee data from the US Hospitalized Adult Influenza Vaccine Effectiveness Network database. Enrolled patients were ≥ 18 years vaccinated for the current influenza season and admitted with an acute respiratory illness. Patient or surrogate interviews and medical chart abstractions were performed, and influenza vaccinations were confirmed by vaccine providers. Influenza PCR testing was performed in a research lab. Statistical analyses were performed with STATA and R using Pearson’s chi-squared, Kruskal-Wallis and Wilcoxon rank-sum tests and multivariate logistic regression. Results 1236 patients met study criteria, and 235 (19%) tested positive for influenza. Demographics, vaccines and comorbidities were similar between the two groups (Table 1) except for morbid obesity, which was more common in influenza negative patients (13% vs 8%, p = 0.04), and immunosuppression, which was more common in the influenza positive (63% vs 54%, p = 0.01). Logistic regression analysis demonstrated older patients (OR 1.47, 95% CI 1.03–2.10) and immunosuppressed patients (OR 1.56, 1.15–2.12) were at increased risk for influenza (Table 2 and Figure 1). Immunosuppression also increased the risk for influenza A/H3N2 (OR 1.86, 95% CI 1.25–2.75). A sensitivity analysis was performed on patients who self-reported influenza vaccination for the current season without vaccine verification and demonstrated increased risk of influenza in older adults (OR 1.66, 95% CI 1.16–2.39). Table 1: Demographics of influenza positive versus influenza negative patients in influenza vaccinated, hospitalized patients. Table 2: Logistic regression analyses of vaccinated, hospitalized influenza positive patients; vaccinated, hospitalized patients with influenza A subtypes and self-reported vaccinated, hospitalized influenza positive patients. Figure 1: Predicted Probability of Hospitalization with Influenza, Influenza A/H1N1 and Influenza A/H3N2 in Vaccinated Patients by Age. Conclusion Our study demonstrated an increased risk of influenza vaccine failure in older patients and immunosuppressed patients. These groups are also at increased risk for influenza complications. To improve protection of these patients against future influenza illnesses, more effective vaccines are needed, and more research on ring vaccination should be pursued. Disclosures All Authors: No reported disclosures

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An Antigenic Thrift-Based Approach to Influenza Vaccine Design

Vaccines ◽

10.3390/vaccines9060657 ◽

2021 ◽

Vol 9 (6) ◽

pp. 657

Author(s):

Jai S. Bolton ◽

Hannah Klim ◽

Judith Wellens ◽

Matthew Edmans ◽

Uri Obolski ◽

...

Keyword(s):

Influenza Vaccine ◽

Influenza Season ◽

Vaccine Design ◽

Antigenic Drift ◽

Influenza Vaccines ◽

Immune Protection ◽

Immune Selection ◽

Drift Theory ◽

Gradual Accumulation ◽

Additional Constraints

The antigenic drift theory states that influenza evolves via the gradual accumulation of mutations, decreasing a host’s immune protection against previous strains. Influenza vaccines are designed accordingly, under the premise of antigenic drift. However, a paradox exists at the centre of influenza research. If influenza evolved primarily through mutation in multiple epitopes, multiple influenza strains should co-circulate. Such a multitude of strains would render influenza vaccines quickly inefficacious. Instead, a single or limited number of strains dominate circulation each influenza season. Unless additional constraints are placed on the evolution of influenza, antigenic drift does not adequately explain these observations. Here, we explore the constraints placed on antigenic drift and a competing theory of influenza evolution – antigenic thrift. In contrast to antigenic drift, antigenic thrift states that immune selection targets epitopes of limited variability, which constrain the variability of the virus. We explain the implications of antigenic drift and antigenic thrift and explore their current and potential uses in the context of influenza vaccine design.

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Influenza Vaccine Effectiveness in Preventing Admissions With Influenza During the 2014-2015 Influenza Season: A Test-Negative Hospital-Based Study, in the Valencia Hospital Network for the Study of Influenza and Respiratory Viruses Disease, Valencia (Spain)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofv133.363 ◽

2015 ◽

Vol 2 (suppl_1) ◽

Author(s):

Joan Puig-Barberà ◽

Ainara Mira-Iglesias ◽

Miguel Tortajada-Girbés ◽

F. Xavier López-Labrador ◽

Ángel Belenguer-Varea ◽

...

Keyword(s):

Influenza Vaccine ◽

Influenza Season ◽

Respiratory Viruses ◽

Vaccine Effectiveness

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Effectiveness of Influenza Vaccines in the HIVE household cohort over 8 years: is there evidence of indirect protection?

10.1101/2021.02.16.21251827 ◽

2021 ◽

Author(s):

Ryan E. Malosh ◽

Joshua G. Petrie ◽

Amy Callear ◽

Rachel Truscon ◽

Emileigh Johnson ◽

...

Keyword(s):

Influenza Vaccine ◽

Influenza A ◽

Vaccine Coverage ◽

Influenza Virus Infection ◽

Influenza Vaccines ◽

Mixed Effect ◽

Vaccination Programs ◽

Vaccine Recommendations ◽

Influenza A H1n1 ◽

Low Coverage

AbstractBackgroundThe evidence that influenza vaccination programs regularly provide protection to unvaccinated individuals (i.e. indirect effects) of a community is lacking. We sought to determine the direct, indirect, and total effects of influenza vaccine in the Household Influenza Vaccine Evaluation (HIVE) cohort.MethodsUsing longitudinal data from the HIVE cohort from 2010-11 through 2017-18, we estimated direct, indirect, and total influenza vaccine effectiveness (VE) and the incidence rate ratio of influenza virus infection using adjusted mixed-effect Poisson regression models. Total effectiveness was determined through comparison of vaccinated members of full or partially vaccinated households to unvaccinated individuals in completely unvaccinated households.ResultsThe pooled, direct VE against any influenza was 30.2% (14.0-43.4). Direct VE was higher for influenza A/H1N1 43.9% (3.9 to 63.5) and B 46.7% (17.2 to 57.5) than A/H3N2 31.7% (10.5 to 47.8); and was higher for young children 42.4% (10.1 to 63.0) than adults 18.6% (−6.3 to 37.7). Influenza incidence was highest in completely unvaccinated households (10.6 per 100 person-seasons) and lower at all other levels of household vaccine coverage. We found little evidence of indirect VE after adjusting for potential confounders. Total VET was 56.4% (30.1-72.9) in low coverage, 43.2% (19.5-59.9) in moderate coverage, and 33.0% (12.1 to 49.0) in fully vaccinated households.ConclusionInfluenza vaccines may have a benefit above and beyond the direct effect but that effect in this study was small. While there may be exceptions, the goal of global vaccine recommendations should remain focused on provision of documented, direct protection to those vaccinated.

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Depletion-of-susceptibles bias in influenza vaccine waning studies: how to ensure robust results

10.1101/19003616 ◽

2019 ◽

Author(s):

M. Lipsitch ◽

E. Goldstein ◽

G.T. Ray ◽

B. Fireman

Keyword(s):

Observational Study ◽

Influenza Vaccine ◽

Randomized Trial ◽

Study Design ◽

Null Hypothesis ◽

Influenza Season ◽

Calendar Time ◽

Future Studies ◽

Biased Estimates ◽

Induced Immunity

SUMMARYVaccine effectiveness (VE) studies are subject to biases due to depletion of at-risk persons or of highly susceptible persons at different rates from different groups (depletion-of-susceptibles bias), a problem that can also lead to biased estimates of waning effectiveness, including spurious inference of waning when none exists. An alternative study design to identify waning is to study only vaccinated persons, and compare for each day the incidence in persons with earlier or later dates of vaccination. Prior studies suggested under what conditions this alternative would yield correct estimates of waning. Here we define the depletion-of-susceptibles process formally and show mathematically that for influenza vaccine waning studies, a randomized trial or corresponding observational study that compares incidence at a specific calendar time among individuals vaccinated at different times before the influenza season begins will not be vulnerable depletion-of-susceptibles bias in its inference of waning under the null hypothesis that none exists, and will – if waning does actually occur – underestimate the extent of waning. Such a design is thus robust in the sense that a finding of waning in that inference framework reflects actual waning of vaccine-induced immunity. We recommend such a design for future studies of waning, whether observational or randomized.

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Start of the influenza season 2008-9 in Europe - increasing influenza activity moving from West to East dominated by A(H3N2)

Eurosurveillance ◽

10.2807/ese.14.03.19097-en ◽

2009 ◽

Vol 14 (3) ◽

Author(s):

N Goddard ◽

P Zucs ◽

B Ciancio ◽

F Plata ◽

O Hungnes ◽

...

Keyword(s):

Influenza Virus ◽

Influenza Vaccine ◽

Northern Hemisphere ◽

Virus Type ◽

Influenza Season ◽

Type A ◽

Neuraminidase Inhibitors ◽

Influenza Activity

The influenza season 2008-9 started in week 49 of 2008 and is so far characterised by influenza virus type A subtype H3N2. Isolates of this subtype that were tested proved susceptible to neuraminidase inhibitors, but resistant to M2 inhibitors. The circulating A(H3N2) viruses are antigenically similar to the component in the current northern hemisphere influenza vaccine.

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The impact of the 2009 influenza A(H1N1) pandemic on attitudes of healthcare workers toward seasonal influenza vaccination 2010/11

Eurosurveillance ◽

10.2807/ese.16.17.19854-en ◽

2011 ◽

Vol 16 (17) ◽

Author(s):

C Brandt ◽

H F Rabenau ◽

S Bornmann ◽

R Gottschalk ◽

S Wicker

Keyword(s):

Medical Students ◽

Influenza Vaccine ◽

Influenza Vaccination ◽

Healthcare Workers ◽

Influenza A ◽

Influenza Season ◽

University Hospital ◽

The Public ◽

Influenza A H1n1 ◽

The Impact

The emergence of the influenza A(H1N1)2009 virus provided a major challenge to health services around the world. However, vaccination rates for the public and for healthcare workers (HCWs) have remained low. We performed a study to review the reasons put forward by HCWs to refuse immunisation with the pandemic vaccine in 2009/10 and characterise attitudes in the influenza season 2010/11 due to the emergence of influenza A(H1N1)2009. A survey among HCWs and medical students in the clinical phase of their studies was conducted, using an anonymous questionnaire, at a German university hospital during an influenza vaccination campaign. 1,366 of 3,900 HCWs (35.0%) were vaccinated in the 2010/11 influenza season. Of the vaccinated HCWs, 1,323 (96.9%) completed the questionnaire in addition to 322 vaccinated medical students. Of the 1,645 vaccinees who completed the questionnaire, 712 had not been vaccinated against the influenza A(H1N1)2009 virus in the 2009/10 season. The main reason put forward was the objection to the AS03 adjuvants (239/712, 33.6%). Of the HCWs and students surveyed, 270 of 1,645 (16.4%) stated that the pandemic had influenced their attitude towards vaccination in general. Many German HCWs remained unconvinced of the safety of the pandemic (adjuvanted) influenza vaccine. For this reason, effective risk communication should focus on educating the public and HCWs about influenza vaccine safety and the benefits of vaccination.

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