Live attenuated influenza vaccine effectiveness against hospitalisation due to laboratory-confirmed influenza in children two to six years of age in England in the 2015/16 season

Edmunds

Human Vaccines & Immunotherapeutics

et al. 2019

In Hong Kong, universal varicella vaccination was introduced in July 2014 with a two-dose schedule but the vaccines had been available in the private market since 1996. With data from varicella notification and surveys on immunization coverage, we used the screening method to estimate dose-specific varicella vaccine effectiveness (VE) among preschool children in Hong Kong before universal vaccination. We estimated the VE of one-and two-dose varicella vaccination against all notified varicella as 69.4% (95% confidence interval (95% CI) 69.5-71.2) and 93.4% (95% CI 91.7-94.7), respectively. We found that VE did not decrease with time since receipt. Varicella vaccine was more effective against complications (85.4% [95% CI 48.8-95.8] for one dose and 100% [95% CI -Inf to 100] for two doses) and against hospital admission (75.2% [95% CI 53.4-86.8] for one dose and 93.1% [95% CI 47.1-99.1] for two doses). Lower protection of one-dose varicella vaccine resulted in breakthrough varicella. Under universal vaccination, second-dose varicella vaccine (given as combined measles, mumps, rubella and varicella vaccine) was first scheduled for children when they reach primary one (about 6 years of age) and was recently advanced to 18 months of age. Shortening the interval between the first dose and second dose of varicella vaccination should reduce breakthrough varicella and outbreaks in preschool. ARTICLE HISTORY

Section: Estimation Of Vementioning

confidence: 99%

Varicella vaccine dose depended effectiveness and waning among preschool children in Hong Kong

Edmunds

Human Vaccines & Immunotherapeutics

et al. 2019

“…In the United Kingdom, annual single-dose LAIV given to children aged 2-16 years since 2013 has significantly reduced severe influenza disease. 6 Pre-licensure and early post-marketing surveillance data showed that LAIV-protection was comparable to inactivated vaccines. 7 Animal models of influenza infection demonstrate increased density and duration of pneumococcal carriage.…”

Section: Introductionmentioning

confidence: 99%

Effect of Live Attenuated Influenza Vaccine on Pneumococcal Carriage

Rylance

Pojar

et al. 2018

Preprint

The widely used nasally-administered Live Attenuated Influenza Vaccine (LAIV) alters the dynamics of naturally occurring nasopharyngeal carriage of Streptococcus pneumoniae in animal models. Using a human experimental model (serotype 6B) we tested two hypotheses: 1) LAIV increased the density of S. pneumoniae in those already colonised; 2) LAIV administration promoted colonisation. Randomised, blinded administration of LAIV or nasal placebo either preceded bacterial inoculation or followed it, separated by a 3-day interval. The presence and density of S. pneumoniae was determined from nasal washes by bacterial culture and PCR. Overall acquisition for bacterial carriage were not altered by prior LAIV administration vs. controls (25/55 [45.5%] vs 24/62 [38.7%] respectively, p=0.46). Transient increase in acquisition was detected in LAIV recipients at day 2 (33/55 [60.0%] vs 25/62 [40.3%] in controls, p=0.03). Bacterial carriage densities were increased approximately 10-fold by day 9 in the LAIV recipients (2.82 vs 1.81 log10 titers, p=0.03). When immunisation followed bacterial acquisition (n=163), LAIV did not change area under the bacterial density-time curve (AUC) at day 14 by conventional microbiology (primary endpoint), but significantly reduced AUC to day 27 by PCR (p=0.03). These studies suggest that LAIV may transiently increase nasopharyngeal density of S. pneumoniae. Transmission effects should therefore be considered in the timing design of vaccine schedules.Trial registrationThe study was registered on EudraCT (2014-004634-26)FundingThe study was funded by the Bill and Melinda Gates Foundation and the UK Medical Research Council.

“…In 2014-15, LAIV was effective against B/Yamagata, but not A/H3N2 (41,42). This pattern remained during the 2015-16 season, with low VE against A/ H1N1pdm09 and A/H3N2 strains, but overall effectiveness against B viruses (44,45,47).…”

Section: Review Of Post-licensure Experience: From Early Success To Rmentioning

confidence: 92%

“…These conflicting data have introduced several significant questions and interpretations. The loss of LAIV effectiveness appears to be largely specific to the United States, with sustained VE in Germany, Canada, the United Kingdom, and Finland (36,40,44,45). This suggests that certain vaccination or production strategies particular to the United States could contribute to decreased effectiveness.…”

Section: Conundrums: Disparity Among Laiv Effectiveness Studiesmentioning

confidence: 99%

Perspectives from the Society for Pediatric Research: Decreased Effectiveness of the Live Attenuated Influenza Vaccine

Gill

Schlaudecker

2017

Pediatr Res

The intranasal live attenuated influenza vaccine (LAIV), FluMist, has been widely appreciated by pediatricians, parents, and children alike for its ease of administration. However, concerns regarding lack of effectiveness in recent influenza seasons led to the CDC Advisory Committee on Immunization Practices (ACIP) recommendation to administer inactivated influenza vaccines (IIVs), and not LAIV, during the 2016-17 and 2017-18 seasons. Given that data from previous years demonstrated equivalent and even improved efficacy of LAIV compared with IIV, these recent data were surprising, raising many questions about the potential mechanisms underlying this change. This review seeks to summarize the history of LAIV studies and ACIP recommendations with a focus on the recent decrease in vaccine effectiveness (VE) and discordant results among studies performed in different countries. Decreased VE for A/H1N1pdm09 viruses represents the most consistent finding across studies, as VE has been low every season these viruses predominated since 2010-11. Potential explanations underlying diminished effectiveness include the hypothesis that prior vaccination, reduced thermostability of A/H1N1pdm09, addition of a fourth virus, or reduced replication fitness of A/H1N1pdm09 strains may have contributed to this phenomenon. Ongoing studies and potential alterations to LAIV formulations provide hope for a return of effective LAIV in future influenza seasons.