Efficacy of a Novel Antibody TLR3 Modulator in the Self-Treatment of Common Cold: The ESTUAR Trial

DOI: 10.4236/aid.2015.54026   PDF   HTML   XML   3,059 Downloads   3,689 Views   Citations


Context: Since the discovery of toll-like receptor 3 (TLR3), no specific tools have been developed to modulate its activity in upper respiratory tract viral infections (URTIs). ContafluTM (antibodies to TLR3 cytoplasmic fragment) is the first specific TLR3 modulator that showed efficacy in a mouse model of influenza. Objective: To evaluate the efficacy of Contaflu in URTI. Methods: A double-blind randomized placebo-controlled trial in adults with self-reported URTI (the ESTUAR trial) was conducted in 2012/2013 in Belgium. Adult outpatients started a 7-day treatment course with oral tablets of Contaflu or placebo within 36 h after onset of at least one of 4 typical symptoms of URTI. Patients were examined twice by their general practitioners, on days 2-3 and 10-14 after start of treatment. The primary endpoint was the overall severity of URTI calculated as the sum of Wisconsin Upper Respiratory Symptom Survey (WURSS-21) scores over the follow-up. Independent Student’s t test was used to compare the disease severity between groups. Results: A total of 243 patients were enrolled by 32 investigators (121 Contaflu, 122 placebo); 92% of cases matched ICD codes J00 or J06. Most patients had very mild (41.8%) or mild (18.2%) URTI symptoms. In the ITT cohort, neither primary nor secondary outcome measures (duration of URTI, day-to-day and overall functional impairments) showed statistically significant differences between groups. The rate of adverse events was similar in both groups. In patients with moderate to severe URTI symptoms, Contaflu tended to reduce the overall disease severity, daily symptoms, and to improve the functional state. Due to the small size of the corresponding subgroups, Contaflu efficacy on daily scores was statistically significant (p < 0.05) only 1, 2, and 5 days after start of treatment. Conclusion: Contaflu was ineffective in mild URTI and showed efficacy in moderate to severe URTI cases.

Share and Cite:

Martyushev-Poklad, A. , Bruhwyler, J. , Heijmans, S. and Thiry, M. (2015) Efficacy of a Novel Antibody TLR3 Modulator in the Self-Treatment of Common Cold: The ESTUAR Trial. Advances in Infectious Diseases, 5, 204-217. doi: 10.4236/aid.2015.54026.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Benson, V. and Marano, M.A. (1998) Current Estimates from the National Health Interview Survey, 1995. National Center for Health Statistics. Vital Health Stat 10 (199).
[2] Adler, A.J., Eames, K.T., Funk, S. and Edmunds, W.J. (2014) Incidence and Risk Factors for Influenza-Like-Illness in the UK: Online Surveillance Using Flusurvey. BMC Infectious Diseases, 14, 232.
[3] Molinari, N.A., Ortega-Sanchez, I.R., Messonnier, M.L., Thompson, W.W., Wortley, P.M., Weintraub, E. and Bridges, C.B. (2007) The Annual Impact of Seasonal Influenza in the US: Measuring Disease Burden and Costs. Vaccine, 25, 5086-5096. http://dx.doi.org/10.1016/j.vaccine.2007.03.046
[4] Wu, S., Metcalf, J.P. and Wu, W. (2011) Innate Immune Response to Influenza Virus. Current Opinion in Infectious Diseases, 24, 235-240. http://dx.doi.org/10.1097/QCO.0b013e328344c0e3
[5] van de Sandt, C.E., Kreijtz, J.H. and Rimmelzwaan, G.F. (2012) Evasion of Influenza A Viruses from Innate and Adaptive Immune Responses. Viruses, 4, 1438-1476. http://dx.doi.org/10.3390/v4091438
[6] Iwasaki, A. and Pillai, P.S. (2014) Innate Immunity to Influenza Virus Infection. Nature Reviews. Immunology, 14, 315-328. http://dx.doi.org/10.1038/nri3665
[7] Hurt, A.C., Hui, D.S., Hay, A. and Hayden, F.G. (2015) Overview of the 3rd Isirv-Antiviral Group Conference— Advances in Clinical Management. Influenza and Other Respiratory Viruses, 9, 20-31.
[8] Klepser, M.E. (2014) Socioeconomic Impact of Seasonal (Epidemic) Influenza and the Role of Over-the-Counter Medicines. Drugs, 74, 1467-1479. http://dx.doi.org/10.1007/s40265-014-0245-1
[9] Tripathi, S., White, M.R. and Hartshorn, K.L. (2015) The Amazing Innate Immune Response to Influenza A Virus Infection. Innate Immunity, 21, 73-98. http://dx.doi.org/10.1177/1753425913508992
[10] Epstein, O.I. (2008) Ultralow Doses (History of One Research). Publishing Office of the Russian Academy of Medical Sciences, Moscow. http://materiamedicacompany.com/en/Epstein_eng.pdf
[11] Le Goffic, R., Pothlichet, J., Vitour, D., Fujita, T., Meurs, E., Chignard, M. and Si-Tahar, M. (2007) Cutting Edge: Influenza A Virus Activates TLR3-Dependent Inflammatory and RIG-I-Dependent Antiviral Responses in Human Lung Epithelial Cells. Journal of Immunology, 178, 3368-3372.
[12] Guillot, L., Le Goffic, R., Bloch, S., Escriou, N., Akira, S., Chignard, M. and Si-Tahar, M. (2005) Involvement of Toll-Like Receptor 3 in the Immune Response of Lung Epithelial Cells to Double-Stranded RNA and Influenza A Virus. The Journal of Biological Chemistry, 280, 5571-5580.
[13] Goffic, R.L., Balloy, V., Lagranderie, M., Alexopoulou, L., Escriou, N., Flavell, R., Chignard, M. and Si-Tahar, M. (2006) Detrimental Contribution of the Toll-Like Receptor (TLR)3 to Influenza A Virus-Induced Acute Pneumonia. PLoS Pathogens, 2, e53. http://dx.doi.org/10.1371/journal.ppat.0020053
[14] Burleson, G.R. and Burleson, F.G. (2007) Influenza Virus Host Resistance Model. Methods, 41, 31-37. http://dx.doi.org/10.1016/j.ymeth.2006.09.007
[15] Heads of Medicines Agencies Homeopathic Medicinal Product Working Group (HMPWG) (2007) Points to Consider on Non-Clinical Safety of Homeopathic Medicinal Products of Botanical, Mineral and Chemical Origin. http://www.hma.eu/uploads/media/PtC_HMP_non_biological_safety_01.pdf
[16] Weber, O. (2009) The Role of Viruses in the Etiology and Pathogenesis of Common Cold. In: Eccles, R. and Weber, O., Eds., Common Cold, Birkhauser Advances in Infectious Diseases, Basel, 107-115.
[17] Hewson, C.A., Jardine, A., Edwards, M.R., Laza-Stanca, V. and Johnston, S.L. (2005) Toll-Like Receptor 3 Is Induced by and Mediates Antiviral Activity against Rhinovirus Infection of Human Bronchial Epithelial Cells. Journal of Virology, 79, 12273-12279. http://dx.doi.org/10.1128/JVI.79.19.12273-12279.2005
[18] Barrett, B., Brown, R.L., Mundt, M.P., Thomas, G.R., Barlow, S.K., Highstrom, A.D. and Bahrainian, M. (2009) Validation of a Short Form Wisconsin Upper Respiratory Symptom Survey (WURSS-21). Health and Quality of Life Outcomes, 7, 76. http://dx.doi.org/10.1186/1477-7525-7-76
[19] NIH Health Care Systems Research Collaboratory (2014) Patient-Reported Outcomes. In: Rethinking Clinical Trials: A Living Textbook of Pragmatic Clinical Trials.
[20] Perales-Linares, R. and Navas-Martin, S. (2013) Toll-Like Receptor 3 in Viral Pathogenesis: Friend or Foe? Immunology, 140, 153-167. http://dx.doi.org/10.1111/imm.12143
[21] Osborne, R.H., Norquist, J.M., Elsworth, G.R., Busija, L., Mehta, V., Herring, T. and Gupta, S.B. (2011) Development and Validation of the Influenza Intensity and Impact Questionnaire (FluiiQ?). Value in Health, 14, 687-699. http://dx.doi.org/10.1016/j.jval.2010.12.005

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.