Area under the curve calculations as a tool to compare the efficacy of equine influenza vaccines—a retrospective analysis of three independent field trials

Heldens, J.G.M.; Weststrate, M. W.; Hoven, R. van den

doi:10.1016/s0022-1759(01)00571-3

Cited by 24 publications

(13 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To compare baseline IFN-γ ELISpot responses between G1-6 a 1-way ANOVA was used with Kruskal-Wallis test and Dunn's multiple comparison test. Area under the curve (AUC) analysis can be used in immunological studies as a tool to estimate overall vaccine immunogenicity and durability ( Heldens et al, 2002 ). AUC values for identical time periods post-vaccination were calculated per individual for each time point.…”

Section: Methodsmentioning

confidence: 99%

Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults

et al. 2018

View full text Add to dashboard Cite

BackgroundT-cell responses against highly conserved influenza antigens have been previously associated with protection. However, these immune responses are poorly maintained following recovery from influenza infection and are not boosted by inactivated influenza vaccines. We have previously demonstrated the safety and immunogenicity of two viral vectored vaccines, modified vaccinia virus Ankara (MVA) and the chimpanzee adenovirus ChAdOx1 expressing conserved influenza virus antigens, nucleoprotein (NP) and matrix protein-1 (M1). We now report on the safety and long-term immunogenicity of multiple combination regimes of these vaccines in young and older adults.MethodsWe conducted a Phase I open-label, randomized, multi-center study in 49 subjects aged 18–46 years and 24 subjects aged 50 years or over. Following vaccination, adverse events were recorded and the kinetics of the T cell response determined at multiple time points for up to 18 months.FindingsBoth vaccines were well tolerated. A two dose heterologous vaccination regimen significantly increased the magnitude of pre-existing T-cell responses to NP and M1 after both doses in young and older adults. The fold-increase and peak immune responses after a single MVA-NP + M1 vaccination was significantly higher compared to ChAdOx1 NP + M1. In a mixed regression model, T-cell responses over 18 months were significantly higher following the two dose vaccination regimen of MVA/ChAdOx1 NP + M1.InterpretationA two dose heterologous vaccination regimen of MVA/ChAdOx1 NP + M1 was safe and immunogenic in young and older adults, offering a promising vaccination strategy for inducing long-term broadly cross-reactive protection against influenza A.Funding SourceMedical Research Council UK, NIHR BMRC Oxford.

show abstract

Section: Methodsmentioning

confidence: 99%

Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Other features of the viral titer curve, besides peak viral load or some measure of infection duration, are sometimes used to assess the effectiveness of antiviral treatment (Beggs and Dobrovolny, 2015 ). These include the area under the viral titer curve (AUC) (Ryan et al, 1994 ; Hayden et al, 1999 ; Heldens and van den Hoven, 2002 ; Rayner et al, 2013 ; Beggs and Dobrovolny, 2015 ) or the viral growth and decay rates (Beggs and Dobrovolny, 2015 ). Measurement of these features might allow further differentiation of the role of antiviral mechanism of action in combination therapy, although the value of these measures in terms of clinical benefit to the patient are unclear.…”

Section: Discussionmentioning

confidence: 99%

Investigating Different Mechanisms of Action in Combination Therapy for Influenza

Rodriguez

Dobrovolny

2018

Front. Pharmacol.

View full text Add to dashboard Cite

Combination therapy for influenza can have several benefits, from reducing the emergence of drug resistant virus strains to decreasing the cost of antivirals. However, there are currently only two classes of antivirals approved for use against influenza, limiting the possible combinations that can be considered for treatment. However, new antivirals are being developed that target different parts of the viral replication cycle, and their potential for use in combination therapy should be considered. The role of antiviral mechanism of action in the effectiveness of combination therapy has not yet been systematically investigated to determine whether certain antiviral mechanisms of action pair well in combination. Here, we use a mathematical model of influenza to model combination treatment with antivirals having different mechanisms of action to measure peak viral load, infection duration, and synergy of different drug combinations. We find that antivirals that lower the infection rate and antivirals that increase the duration of the eclipse phase perform poorly in combination with other antivirals.

show abstract

“…Pairwise comparisons were then carried out using Tukey's honestly significant difference (HSD) correction for multiple testing. The area under the curve (AUC) as described by Heldens et al [23] was also calculated by the trapezoidal rule and ANOVA and pairwise comparisons using Tukey's HSD were carried out. All results are presented as mean and standard error of the mean.…”

Section: Discussionmentioning

confidence: 99%

Comparison of primary vaccination regimes for equine influenza: Working towards an evidence‐based regime

Cullinane

Gildea

Weldon

2014

Equine Veterinary Journal

View full text Add to dashboard Cite

SummaryReasons for performing study: Vaccination is crucial to the control of equine influenza (EI). The study was conducted in an effort to lay the groundwork for achieving international harmonisation of regulatory requirements based on scientific evidence of performance of different vaccination regimes. Objectives: To evaluate the effectiveness of 3 different primary vaccination regimes: vaccination with the minimal intervals permitted by the racing authorities; vaccination in accordance with the manufacturer's instructions and vaccination with the longest intervals permitted by the racing authorities. Study design: Randomised, prospective clinical trial. Methods: The 55 seronegative unvaccinated horses in this study were subdivided by age and randomly allocated one of the 3 vaccination regimes. All groups were sampled each time a group was vaccinated and 3-5 weeks post vaccination. Horses were vaccinated with a subunit immune stimulating complex-based vaccine (Equip FT). Antibodies against EI were measured by single radial haemolysis. Results: Lengthening the vaccination intervals increased the immunity gaps between first (V1) and second (V2) doses, and V2 and third dose (V3) but did not inhibit the response to V2 and V3. The response to V2 and V3 was similar irrespective of the regime. Poor responders to V1 were identified in all age groups included in this study but the greatest number of poor responders was among the yearlings. The 2-and 3-year-old horses responded better to vaccination than the weanlings or yearlings. Conclusions: Longer vaccination intervals permitted by racing authorities increase the periods of susceptibility to EI but they may facilitate strategic vaccination prior to times of increased risk of exposure to virus. The study provides the type of evidence-based data necessary to commence meaningful discussion of international harmonisation of EI vaccination requirements.

show abstract

Area under the curve calculations as a tool to compare the efficacy of equine influenza vaccines—a retrospective analysis of three independent field trials

Cited by 24 publications

References 7 publications

Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults

Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults

Investigating Different Mechanisms of Action in Combination Therapy for Influenza

Comparison of primary vaccination regimes for equine influenza: Working towards an evidence‐based regime

Contact Info

Product

Resources

About