Low effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2014/15 mid–season results

Pebody, Richard; Warburton, Fiona; Ellis, Joanna; Andrews, Nicholas; Thompson, Catherine; Wissmann, Beatrix von; Green, H. K.; Cottrell, Simon; Johnston, Jillian; Lusignan, Simon de; Moore, Catherine; Gunson, Rory; Robertson, Christopher; McMenamin, Jim; Zambon, Maria

doi:10.2807/1560-7917.es2015.20.5.21025

Cited by 77 publications

(69 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among the A (H3N2) viruses characterized from swabbed patients, a significant proportion were antigenically drifted from the vaccine component. [2][3][4][5] This low VE could be explained by concomitant A(H3N2) vaccine mismatch and by the immunosenescence process.…”

Section: Discussionmentioning

confidence: 99%

“…1 In the northern hemisphere, the ongoing influenza season was dominated by the A(H3N2) sub-type. [2][3][4][5] The A(H3N2) viruses are known to cause more severe illness with potential for complications especially in the elderly and other risk groups targeted for vaccination than A(H1N1)pdm09 and/or B viruses. 6,7 During the 2014/15 influenza season, a significant proportion of the A (H3N2) viruses characterized antigenically and genetically has demonstrated antigenic drift from the northern hemisphere vaccine component resulting in reduced vaccine effectiveness (VE).…”

Section: Introductionmentioning

confidence: 99%

“…6,7 During the 2014/15 influenza season, a significant proportion of the A (H3N2) viruses characterized antigenically and genetically has demonstrated antigenic drift from the northern hemisphere vaccine component resulting in reduced vaccine effectiveness (VE). [2][3][4][5] Early VE estimates reported from United States (US) 3 United Kingdom (UK) 4 and Canada, 5 were low compared with previous seasons when circulating viruses and vaccine viruses were wellmatched.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Early estimates of 2014/15 seasonal influenza vaccine effectiveness in preventing influenza-like illness in general practice using the screening method in France

Souty

Blanchon

Bonmarin

et al. 2015

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Early estimates of 2014/15 seasonal influenza vaccine effectiveness in preventing influenza-like illness in general practice using the screening method in France

Souty

Blanchon

Bonmarin

et al. 2015

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

“…By the spring-summer of 2014, A(H3N2) viruses belonging to six H3 clades (3C.2, 3C.2a, 3C.2b, 3C.3, 3C.3a, and 3C.3b) were cocirculating globally (18)(19)(20). Initial information gained from HI data indicated antigenic differences between the vaccine strain, A/Texas/50/2012, and circulating viruses from two H3 clades, 3C.2a and 3C.3a.…”

mentioning

confidence: 99%

A Pyrosequencing-Based Approach to High-Throughput Identification of Influenza A(H3N2) Virus Clades Harboring Antigenic Drift Variants

et al. 2017

View full text Add to dashboard Cite

The rapid evolution of influenza A(H3N2) viruses necessitates close monitoring of their antigenic properties so the emergence and spread of antigenic drift variants can be rapidly identified. Changes in hemagglutinin (HA) acquired by contemporary A(H3N2) viruses hinder antigenic characterization by traditional methods, thus complicating vaccine strain selection. Sequence-based approaches have been used to infer virus antigenicity; however, they are time consuming and midthroughput. To facilitate virological surveillance and epidemiological studies, we developed and validated a pyrosequencing approach that enables identification of six HA clades of contemporary A(H3N2) viruses. The identification scheme of viruses of the H3 clades 3C.2, 3C.2a, 3C.2b, 3C.3, 3C.3a, and 3C.3b is based on the interrogation of five single nucleotide polymorphisms (SNPs) within three neighboring HA regions, namely 412 to 431, 465 to 481, and 559 to 571. Two bioinformatics tools, IdentiFire (Qiagen) and FireComb (developed in-house), were utilized to expedite pyrosequencing data analysis. The assay's analytical sensitivity was 10 focus forming units, and respiratory specimens with threshold cycle (C T ) values of Ͻ34 typically produced good quality pyrograms. When applied to 120 A(H3N2) virus isolates and 27 respiratory specimens, the assay displayed 100% agreement with clades determined by HA sequencing coupled with phylogenetics. The multi-SNP analysis described here was readily adopted by another laboratory with pyrosequencing capabilities. The implementation of this approach enhanced the findings from virological surveillance and epidemiological studies between 2013 and 2016, which examined more than 3,000 A(H3N2) viruses.KEYWORDS A(H3N2), genotyping, influenza, pyrosequencing S ince their introduction into the human population in 1968, influenza A(H3N2) viruses have been responsible for seasonal epidemics and associated with both a prolonged duration of the epidemic season and a greater disease severity (1-4). The hemagglutinin (HA) glycoprotein is the major surface antigen of influenza viruses; it is also responsible for the receptor binding and membrane fusion required for entrance into susceptible host cells (5). Decades ago, this glycoprotein was named "hemagglutinin" for its ability to bind and bridge erythrocytes. The other surface antigen, neuraminidase (NA), is a receptor-destroying enzyme (6). As with other seasonal influenza viruses, A(H3N2) viruses undergo genetic and antigenic changes, called antigenic drift,

show abstract

“…However, if there is an antigenic mismatch between vaccine strains and circulating influenza virus strains, the vaccines offer little or no protection, as was the case for the A/H3N2 vaccine component during the 2014-2015 influenza season (27)(28)(29). Furthermore, the production of sufficient vaccine doses is a time-consuming process, as was demonstrated during the influenza pandemic of 2009 caused by A/H1N1pdm09 virus, when in most countries, vaccines became available after the peak of the pandemic (30,31).…”

mentioning

confidence: 99%

Increased Protein Degradation Improves Influenza Virus Nucleoprotein-Specific CD8⁺T Cell ActivationIn Vitrobut Not in C57BL/6 Mice

Altenburg

Sandt

Trierum

et al. 2016

J Virol

View full text Add to dashboard Cite

Due to antigenic drift of influenza viruses, seasonal influenza vaccines need to be updated annually. These vaccines are based on predictions of strains likely to circulate in the next season. However, vaccine efficacy is greatly reduced in the case of a mismatch between circulating and vaccine strains. Furthermore, novel antigenically distinct influenza viruses are introduced into the human population from animal reservoirs occasionally and may cause pandemic outbreaks. To dampen the impact of seasonal and pandemic influenza, vaccines that induce broadly protective and long-lasting immunity are preferred. Because influenza virusspecific CD8؉ T cells are directed mainly against relatively conserved internal proteins, like nucleoprotein (NP), they are highly cross-reactive and afford protection against infection with antigenically distinct influenza virus strains, so-called heterosubtypic immunity. Here, we used modified vaccinia virus Ankara (MVA) as a vaccine vector for the induction of influenza virus NP-specific CD8 ؉ T cells. To optimize the induction of CD8 ؉ T cell responses, we made several modifications to NP, aiming at retaining the protein in the cytosol or targeting it to the proteasome. We hypothesized that these strategies would increase antigen processing and presentation and thus improve the induction of CD8 ؉ T cell responses. We showed that NP with increased degradation rates improved CD8 ؉ T cell activation in vitro if the amount of antigen was limited or if CD8 ؉ T cells were of low functional avidity. However, after immunization of C57BL/6 mice, no differences were detected between modified NP and wild-type NP (NPwt), since NPwt already induced optimal CD8 ؉ T cell responses. IMPORTANCEDue to the continuous antigenic drift of seasonal influenza viruses and the threat of a novel pandemic, there is a great need for the development of novel influenza vaccines that offer broadly protective immunity against multiple subtypes. CD8 ؉ T cells can provide immunity against multiple subtypes of influenza viruses by the recognition of relatively conserved internal antigens. In this study, we aimed at optimizing the CD8 ؉ T cell response to influenza A virus by making modifications to influenza A virus nucleoprotein (NP) expressed from the modified vaccinia virus Ankara (MVA) vaccine vector. These modifications resulted in increased antigen degradation, thereby producing elevated levels of peptides that can be presented on major histocompatibility complex (MHC) class I molecules to CD8 ؉ T cells. Although we were unable to increase the NP-specific immune response in the mouse strain used, this approach may have benefits for vaccine development using less-immunogenic proteins.

show abstract

Low effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2014/15 mid–season results

Cited by 77 publications

References 10 publications

Early estimates of 2014/15 seasonal influenza vaccine effectiveness in preventing influenza-like illness in general practice using the screening method in France

Early estimates of 2014/15 seasonal influenza vaccine effectiveness in preventing influenza-like illness in general practice using the screening method in France

A Pyrosequencing-Based Approach to High-Throughput Identification of Influenza A(H3N2) Virus Clades Harboring Antigenic Drift Variants

Increased Protein Degradation Improves Influenza Virus Nucleoprotein-Specific CD8⁺T Cell ActivationIn Vitrobut Not in C57BL/6 Mice

Contact Info

Product

Resources

About

Low effectiveness of seasonal influenza vaccine in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2014/15 mid–season results

Cited by 77 publications

References 10 publications

Early estimates of 2014/15 seasonal influenza vaccine effectiveness in preventing influenza-like illness in general practice using the screening method in France

Early estimates of 2014/15 seasonal influenza vaccine effectiveness in preventing influenza-like illness in general practice using the screening method in France

A Pyrosequencing-Based Approach to High-Throughput Identification of Influenza A(H3N2) Virus Clades Harboring Antigenic Drift Variants

Increased Protein Degradation Improves Influenza Virus Nucleoprotein-Specific CD8+T Cell ActivationIn Vitrobut Not in C57BL/6 Mice

Contact Info

Product

Resources

About

Increased Protein Degradation Improves Influenza Virus Nucleoprotein-Specific CD8⁺T Cell ActivationIn Vitrobut Not in C57BL/6 Mice