Interim Estimates of 2016–17 Seasonal Influenza Vaccine Effectiveness — United States, February 2017

Flannery, Brendan; Chung, Jessie R.; Thaker, Swathi; Monto, Arnold S.; Martin, Emily T.; Belongia, Edward A.; McLean, Huong Q.; Gaglani, Manjusha; Murthy, Kempapura; Zimmerman, Richard K.; Nowalk, Mary Patricia; Jackson, Michael L.; Jackson, Lisa A.; Foust, Angie; Sessions, Wendy; Berman, LaShondra; Spencer, Sarah; Fry, Alicia M.

doi:10.15585/mmwr.mm6606a3

Cited by 144 publications

(141 citation statements)

References 9 publications

Supporting

Mentioning

132

Contrasting

Order By: Relevance

“…Influenza infection was confirmed using quantitative reverse transcription-PCR (qRT-PCR) (22). During the 2012-13 and 2013-14 seasons, subtypes H3N2 and 2009 pandemic H1N1 (H1N1pdm), respectively, were dominant in the United States (4,23); for this reason, we only had access to H3N2 during the 2012-13 season and H1N1pdm viruses during the 2013-14 season.…”

Section: Methodsmentioning

confidence: 99%

“…Informed consent was obtained from all adults and parents/ guardians of children. Additional details on the vaccine effectiveness studies for which these human samples were originally collected have been published (4,23).…”

Section: Methodsmentioning

confidence: 99%

“…Vaccine effectiveness can vary greatly by season, but the average effectiveness at preventing illness has been estimated to be 59% (2). Even when there is good antigenic match between circulating viruses and vaccine strains, people can become infected despite being vaccinated earlier in the same season, a situation known as vaccine failure (3)(4)(5).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Deep Sequencing Reveals Potential Antigenic Variants at Low Frequencies in Influenza A Virus-Infected Humans

Dinis

Florek

Fatola

et al. 2016

J Virol

Self Cite

103

121

View full text Add to dashboard Cite

Influenza vaccines must be frequently reformulated to account for antigenic changes in the viral envelope protein, hemagglutinin (HA). The rapid evolution of influenza virus under immune pressure is likely enhanced by the virus's genetic diversity within a host, although antigenic change has rarely been investigated on the level of individual infected humans. We used deep sequencing to characterize the between-and within-host genetic diversity of influenza viruses in a cohort of patients that included individuals who were vaccinated and then infected in the same season. We characterized influenza HA segments from the predominant circulating influenza A subtypes during the 2012-2013 (H3N2) and 2013-2014 (pandemic H1N1; H1N1pdm) flu seasons. We found that HA consensus sequences were similar in nonvaccinated and vaccinated subjects. In both groups, purifying selection was the dominant force shaping HA genetic diversity. Interestingly, viruses from multiple individuals harbored low-frequency mutations encoding amino acid substitutions in HA antigenic sites at or near the receptor-binding domain. These mutations included two substitutions in H1N1pdm viruses, G158K and N159K, which were recently found to confer escape from virusspecific antibodies. These findings raise the possibility that influenza antigenic diversity can be generated within individual human hosts but may not become fixed in the viral population even when they would be expected to have a strong fitness advantage. Understanding constraints on influenza antigenic evolution within individual hosts may elucidate potential future pathways of antigenic evolution at the population level. IMPORTANCEInfluenza vaccines must be frequently reformulated due to the virus's rapid evolution rate. We know that influenza viruses exist within each infected host as a "swarm" of genetically distinct viruses, but the role of this within-host diversity in the antigenic evolution of influenza has been unclear. We characterized here the genetic and potential antigenic diversity of influenza viruses infecting humans, some of whom became infected despite recent vaccination. Influenza virus between-and within-host genetic diversity was not significantly different in nonvaccinated and vaccinated humans, suggesting that vaccine-induced immunity does not exert strong selective pressure on viruses replicating in individual people. We found low-frequency mutations, below the detection threshold of traditional surveillance methods, in nonvaccinated and vaccinated humans that were recently associated with antibody escape. Interestingly, these potential antigenic variants did not reach fixation in infected people, suggesting that other evolutionary factors may be hindering their emergence in individual humans. S easonal influenza A epidemics cause an estimated 3 to 5 million cases of severe respiratory illness each year, resulting in approximately 250,000 to 500,000 deaths worldwide (1). Available influenza vaccines only provide moderate protection against infection and illness...

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Deep Sequencing Reveals Potential Antigenic Variants at Low Frequencies in Influenza A Virus-Infected Humans

Dinis

Florek

Fatola

et al. 2016

J Virol

Self Cite

103

121

View full text Add to dashboard Cite

show abstract

“…Notwithstanding the possibility of all of these forms of bias, test-negative studies have reported plausible results, including very low or no effectiveness of severely mismatched vaccine formulations for certain seasons such as 2014-15 (42)(43)(44) and for elderly in multiple seasons (30,40). The test-negative study design was used in a study that argued that receipt of seasonal influenza vaccine was associated with increased risk of H1N1pdm morbidity during the 2009 pandemic period in Canada (17) It was also used to demonstrate that live attenuated vaccine was less effective than TIV in adults (45) and children (46).…”

Section: A Causal Account Of the Test-negative Designmentioning

confidence: 99%

Observational studies and the difficult quest for causality: lessons from vaccine effectiveness and impact studies

2016

View full text Add to dashboard Cite

Although randomized placebo-controlled trials (RCT) are critical to establish efficacy of vaccines at the time of licensure, important remaining questions about vaccine effectiveness (VE) -used here to include individual-level measures and population-wide impact of vaccine programs --can only be answered once the vaccine is in use, from observational studies. However, such studies are inherently at risk for bias. Using a causal framework and illustrating with examples we review newer approaches to detecting and avoiding confounding and selection bias in three major classes of observational study design: cohort, case-control, and ecological studies. Studies of influenza VE, especially in seniors, are an excellent demonstration of the challenges of detecting and reducing such bias, and so we use influenza VE as a running example. We take a fresh look at the time-trend studies often dismissed as "ecological." Such designs are the only observational study design that can measure the overall effect of a vaccination program (indirect (herd) as well as direct effects), and are in fact already an important part of the evidence base for several vaccines currently in use. Despite the great strides towards more robust observational study designs, challenges lie ahead for evaluating best practices for achieving robust unbiased results from observational studies. This is critical for evaluation of national and global vaccine program effectiveness.

show abstract

“…Moreover, A (H3N2) viruses are shown to undergo changes in their receptor-binding specificity, which might result in genetic changes during their growth in eggs. These egg-adapted changes alter the antigenic properties of candidate vaccine viruses and contribute to a lower VE [10].…”

Section: Antigenic Drift and Antigenic Shiftmentioning

confidence: 99%

Influenza vaccine response: future perspectives

Mameli

D’Auria

Erba

et al. 2017

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

Interim Estimates of 2016–17 Seasonal Influenza Vaccine Effectiveness — United States, February 2017

Cited by 144 publications

References 9 publications

Deep Sequencing Reveals Potential Antigenic Variants at Low Frequencies in Influenza A Virus-Infected Humans

Deep Sequencing Reveals Potential Antigenic Variants at Low Frequencies in Influenza A Virus-Infected Humans

Observational studies and the difficult quest for causality: lessons from vaccine effectiveness and impact studies

Influenza vaccine response: future perspectives

Contact Info

Product

Resources

About