The effect of zanamivir treatment on the early immune response to influenza vaccination

Mykkeltvedt, Eva; Sjursen, Håkon; Haaheim, Lars R.

doi:10.1016/s0264-410x(01)00219-5

Cited by 19 publications

(13 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This work focuses on the effects of Se on immune function. Sample size was determined from previous studies [11], [12] and designed to give 80% power. In order to be able to detect a range of 1 standard deviation between the groups with a power of 80%, a sample size of 144 (or 24 in each group) was considered to be sufficient.…”

Section: Methodsmentioning

confidence: 99%

Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults

et al. 2017

View full text Add to dashboard Cite

SummaryBackground & aimsMortality resulting from influenza (flu) virus infections occurs primarily in the elderly through declining immunity. Studies in mice have suggested beneficial effects of selenium (Se) supplementation on immunity to flu but similar evidence is lacking in humans. A dietary intervention study was therefore designed to test the effects of Se-supplementation on a variety of parameters of anti-flu immunity in healthy subjects aged 50–64 years.MethodsA 12-week randomized, double-blinded, placebo-controlled clinical trial (ClinicalTrials.govNCT00279812) was undertaken in six groups of individuals with plasma Se levels <110 ng/mL. Four groups were given daily capsules of yeast enriched with 0 μg Se/day (SeY-0/d; n = 20), 50 μg Se/d (SeY-50/d; n = 18), 100 μg Se/d (SeY-100/d; n = 21) or 200 μg Se/d (SeY-200/d; n = 23). Two groups were given onion-containing meals with either <1 μg Se/d (SeO-0/d; n = 17) or 50 μg Se/d (SeO-50/d; n = 18). Flu vaccine was administrated at week 10 and immune parameters were assessed until week 12.ResultsPrimary study endpoints were changes in cellular and humoral immune responses. Supplementation with SeY and SeO affected different aspects of cellular immunity. SeY increased Tctx-ADCC cell counts in blood (214%, SeY-100/d) before flu vaccination and a dose-dependent increase in T cell proliferation (500%, SeY-50/100/200/d), IL-8 (169%, SeY-100/d) and IL-10 (317%, SeY-200/d) secretion after in vivo flu challenge. Positive effects were contrasted by lower granzyme B content of CD8 cells (55%, SeY-200/d). SeO (Se 50 μg/d) also enhanced T cell proliferation after vaccination (650%), IFN-γ (289%), and IL-8 secretion (139%), granzyme (209%) and perforin (190%) content of CD8 cells but inhibited TNF-α synthesis (42%). Onion on its own reduced the number of NKT cells in blood (38%). These effects were determined by comparison to group-specific baseline yeast or onion control groups. Mucosal flu-specific antibody responses were unaffected by Se-supplementation.ConclusionSe-supplementation in healthy human adults with marginal Se status resulted in both beneficial and detrimental effects on cellular immunity to flu that was affected by the form of Se, supplemental dose and delivery matrix. These observations call for a thorough evaluation of the risks and benefits associated with Se-supplementation.

show abstract

Section: Methodsmentioning

confidence: 99%

Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults

et al. 2017

View full text Add to dashboard Cite

show abstract

“…This means that inhaled zanamivir could reach a high enough concentration to reduce the immune response, if it is administered at a high dose or for a long period, or if the patient is very susceptible. In fact, a double-blind, placebo-controlled trial 137 using healthy volunteers to investigate the effect of zanamivir treatment (20 mg/day for 14 days) on the humoral immune response to influenza vaccine showed that the zanamivir group responded with significantly lower antibody titres to the H1N1. Pro-inflammatory cytokines, including interleukin 6, tumour necrosis factor alpha, interferon gamma and other chemokines, were almost completely suppressed in the viral challenge RCT using a very high dose (600 mg) of intravenous zanamivir before inoculation of the influenza virus in human adults.…”

mentioning

confidence: 99%

Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data

Heneghan

Onakpoya

Jones

et al. 2016

Health Technol Assess

View full text Add to dashboard Cite

BackgroundNeuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide.ObjectivesTo (1) describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports (CSRs) of published and unpublished randomised, placebo-controlled trials and regulatory comments; and (2) determine the effect of oseltamivir (Tamiflu®, Roche) treatment on mortality in patients with 2009A/H1N1 influenza.MethodsWe searched trial registries, electronic databases and corresponded with regulators and sponsors to identify randomised trials of NIs. We requested full CSRs and accessed regulators’ comments. We included only those trials for which we had CSRs. To examine the effects of oseltamivir on 2009A/H1N1 influenza mortality, we requested individual patient data (IPD) from corresponding authors of all included observational studies.ResultsEffect of oseltamivir and zanamivir (Relenza®, GlaxoSmithKline) in the prevention and treatment of influenza: Oseltamivir reduced the time to first alleviation of symptoms in adults by 16.8 hours [95% confidence interval (CI) 8.4 to 25.1 hours]. Zanamivir reduced the time to first alleviation of symptoms in adults by 0.60 days (95% CI 0.39 to 0.81 days). Oseltamivir reduced unverified pneumonia in adult treatment [risk difference (RD) 1.00%, 95% CI 0.22% to 1.49%]; similar findings were observed with zanamivir prophylaxis in adults (RD 0.32%, 95% CI 0.09% to 0.41%). Oseltamivir treatment of adults increased the risk of nausea (RD 3.66%, 95% CI 0.90% to 7.39%) and vomiting (RD 4.56%, 95% CI 2.39% to 7.58%). In the treatment of children, oseltamivir induced vomiting (RD 5.34%, 95% CI 1.75% to 10.29%). Both oseltamivir and zanamivir prophylaxis reduced the risk of symptomatic influenza in individuals (oseltamivir RD 3.05%, 95% CI 1.83% to 3.88%; zanamivir RD 1.98%, 95% CI 0.98% to 2.54%) and in households (oseltamivir RD 13.6%, 95% CI 9.52% to 15.47%; zanamivir RD 14.84%, 95% CI 12.18% to 16.55%). Oseltamivir increased psychiatric adverse events in the combined on- and off-treatment periods (RD 1.06%, 95% CI 0.07% to 2.76%) and the risk of headaches while on treatment (RD 3.15%, 95% CI 0.88% to 5.78%).Effect of oseltamivir on mortality in patients with 2009A/H1N1 influenza: Analysis of summary data of 30 studies as well as IPD of four studies showed evidence of time-dependent bias. After adjusting for time-dependent bias and potential confounding variables, competing risks analysis of the IPD showed insufficient evidence that oseltamivir reduced the risk of mortality (hazard ratio 1.03, 95% CI 0.64 to 1.65).ConclusionsOseltamivir and zanamivir cause small reductions in the time to first alleviation of influenza symptoms in adults. The use of oseltamivir increases the risk of nausea, vomiting, psychiatric events in adults and vomiting in children. Oseltamivir has no protective effect on mortality among patients with 2009A/H1N1 influenza. Prophylaxis with either NI may reduce symptomatic influenza in individuals and in households. The balance between benefits and harms should be considered when making decisions about use of NIs for either prophylaxis or treatment of influenza.Study registrationThis study is registered as PROSPERO CRD42012002245.FundingThe National Institute for Health Research Health Technology Assessment programme.

show abstract

“…In healthy subjects, treatment with zanamivir did not influence the rapidity or the magnitude of the immune response to parenteral influenza vaccination [15], suggesting that the neuraminidase inhibitors can be safely used to provide protection against influenza during the first week post-vaccination and antiviral drug can be combined with vaccination in an effort to protect against influenza infection.…”

Section: Discussionmentioning

confidence: 98%

The kinetics of the systemic and local immune response to parenteral influenza vaccination

Madhun

Haaheim

Jönsson

et al. 2004

International Congress Series

Self Cite

View full text Add to dashboard Cite

The effect of zanamivir treatment on the early immune response to influenza vaccination

Cited by 19 publications

References 18 publications

Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults

Selenium supplementation has beneficial and detrimental effects on immunity to influenza vaccine in older adults

Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data

The kinetics of the systemic and local immune response to parenteral influenza vaccination

Contact Info

Product

Resources

About