Dataset Information

Viral interference and the live-attenuated intranasal influenza vaccine: Results from a pediatric cohort with cystic fibrosis.

ABSTRACT:

Background

The objective of this study was to explore the effects of viral co-detection in individuals recently vaccinated with the live-attenuated intranasal influenza virus vaccine (LAIV) on the detection of influenza RNA.

Methods

Before the 2013-2014 influenza season, nasal swabs were obtained from 59 pediatric participants with cystic fibrosis (CF) and 17 of their healthy siblings immediately before vaccination and 4 times during the week of follow-up. Real-time RT-PCR assays were used to detect influenza RNA. Co-detection of a non-influenza respiratory virus (NIRV) at the time of vaccination was determined by a multiplex RT-PCR assay. Differences in the proportions and rates of influenza detection and their 95% credible intervals (CrI) were estimated.

Results

Influenza RNA was detected in 16% fewer participants (95% CrI: -7, 39%) throughout follow-up in the NIRV-positive group compared with the NIRV-negative group (59% vs. 75%). This was also observed in participants with CF alone (66% vs. 74%; RD = 8% 95% CrI: -16, 33%) as well as in healthy participants only (75% vs. 30%; RD = 45%, 95% CrI: -2, 81%). Influenza was detected in NIRV-negative subjects for 0.49 d more compared with NIRV-positive subjects (95% CrI: -0.37, 1.26).

Conclusion

The observed proportion of subjects in whom influenza RNA was detected and the duration of detection differed slightly between NIRV- positive and -negative subjects. However, wide credible intervals for the difference preclude definitive conclusions. If true, this observed association may be related to a recent viral respiratory infection, a phenomenon known as viral interference.

SUBMITTER: Boikos C

PROVIDER: S-EPMC5489283 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Viral interference and the live-attenuated intranasal influenza vaccine: Results from a pediatric cohort with cystic fibrosis.

Boikos Constantina C Papenburg Jesse J Martineau Christine C Joseph Lawrence L Scheifele David D Chilvers Mark M Lands Larry C LC De Serres Gaston G Quach Caroline C

Human vaccines & immunotherapeutics 20170308 6

<h4>Background</h4>The objective of this study was to explore the effects of viral co-detection in individuals recently vaccinated with the live-attenuated intranasal influenza virus vaccine (LAIV) on the detection of influenza RNA.<h4>Methods</h4>Before the 2013-2014 influenza season, nasal swabs were obtained from 59 pediatric participants with cystic fibrosis (CF) and 17 of their healthy siblings immediately before vaccination and 4 times during the week of follow-up. Real-time RT-PCR assays ...[more]

PMID: 28273006

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Project description:BackgroundThe burden of influenza is increasingly recognised in Africa. The WHO recommends introducing influenza vaccination to high-risk groups: pregnant women, children <5 years, and the elderly. The Gambia currently has no influenza vaccination policy, but the NASIMMUNE study, a clinical trial of intranasal live attenuated influenza vaccines (LAIV) in young children provided an opportunity to study maternal attitudes towards LAIV for the first time in sub-Saharan Africa. We assess acceptability of LAIV, influenza knowledge and attitudes towards influenza vaccination in Gambian women. Additionally, we investigate predictors of willingness to receive influenza vaccine (intent) in pregnancy or seasonally for children <5.MethodsA cross-sectional survey was conducted in Gambian women at two urban health facilities. To assess LAIV acceptability, the exposure group (women whose children had received LAIV during the NASIMMUNE study) were compared to a control group (women whose children were not enrolled in the NASIMMUNE study). Demographics and health belief constructs were analysed as predictors of influenza knowledge and vaccine intent.FindingsThe exposure group (n = 150) expressed a higher preference for a nasal spray vaccine than an injection compared to the control group (n = 304) (93.3% vs. 34.9%, OR = 26.15, p < 0.0001). Those in the exposure group who preferred the nasal spray found it less distressing, safer or equally safe, and easier or equally easy to give (all p < 0.001) than injections. Influenza knowledge increased with education level (p = 0.006 for higher education vs. none), and varied between sites (p = 0.0005). Vaccine intent was >98%, but no association with influenza knowledge or difference between groups was observed. Various health belief constructs were associated with vaccine intent.ConclusionLAIV acceptability was higher in those with first-hand experience. Influenza vaccine intent was also high. Incorporation of seasonal LAIV into the childhood immunisation schedule in The Gambia would be feasible, particularly if combined with community-based health education.

Project description:BACKGROUND: H5N1 influenza vaccines, including live intranasal, appear to be relatively less immunogenic compared to seasonal analogs. The main influenza virus surface glycoprotein hemagglutinin (HA) of highly pathogenic avian influenza viruses (HPAIV) was shown to be more susceptible to acidic pH treatment than that of human or low pathogenic avian influenza viruses. The acidification machinery of the human nasal passageway in response to different irritation factors starts to release protons acidifying the mucosal surface (down to pH of 5.2). We hypothesized that the sensitivity of H5 HA to the acidic environment might be the reason for the low infectivity and immunogenicity of intranasal H5N1 vaccines for mammals. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that original human influenza viruses infect primary human nasal epithelial cells at acidic pH (down to 5.4), whereas H5N1 HPAIVs lose infectivity at pH ? 5.6. The HA of A/Vietnam/1203/04 was modified by introducing the single substitution HA2 58K?I, decreasing the pH of the HA conformational change. The H5N1 reassortants containing the indicated mutation displayed an increased resistance to acidic pH and high temperature treatment compared to those lacking modification. The mutation ensured a higher viral uptake as shown by immunohistochemistry in the respiratory tract of mice and 25 times lower mouse infectious dose??. Moreover, the reassortants keeping 58K?I mutation designed as a live attenuated vaccine candidate lacking an NS1 gene induced superior systemic and local antibody response after the intranasal immunization of mice. CONCLUSION/SIGNIFICANCE: Our finding suggests that an efficient intranasal vaccination with a live attenuated H5N1 virus may require a certain level of pH and temperature stability of HA in order to achieve an optimal virus uptake by the nasal epithelial cells and induce a sufficient immune response. The pH of the activation of the H5 HA protein may play a substantial role in the infectivity of HPAIVs for mammals.

Dataset Information

Viral interference and the live-attenuated intranasal influenza vaccine: Results from a pediatric cohort with cystic fibrosis.

Background

Methods

Results

Conclusion

Publications

Viral interference and the live-attenuated intranasal influenza vaccine: Results from a pediatric cohort with cystic fibrosis.

Similar Datasets

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