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You are here: Home → 2009 Symposia → XI International Symposium on Respiratory Viral Infections → Oral abstracts → Combinations of immunomodulators and specific antivirals: A new treatment paradigm for Influenza

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Combinations of immunomodulators and specific antivirals: A new treatment paradigm for Influenza
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Clinical features of human influenza A(H5N1) infection in Vietnam: 2004-2006
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Combinations of immunomodulators and specific antivirals: A new treatment paradigm for Influenza

Session VII: Altmeyer

Title of Contribution: Combinations of immunomodulators and specific antivirals: A new treatment paradigm for Influenza

Author(s): Geeta Sharma, Vishal Pendharker, DC Sharma, Xue Huiyu, Isabelle Lepage Nefkins and Ralf Altmeyer

Affiliation(s): CombinatoRx Singapore, 11Biopolis Way, 08-05/06, Helios, Singapore-138667

Abstract:

Objective: Our goal is to develop novel Influenza drugs with significantly improved therapeutic benefit over current standard of care neuraminidase inhibitors. We combined the specifically targeted antiviral oseltamivir with immunomodulators likeC-10803 and evaluated the effect of the drug combination on mortality of mice infected with Influenza A/ H1N1 virus.
Background: The morbidity and mortality associated with severe Influenza infections, particularly by the H5N1 virus, have been attributed to uncontrolled virus induced inflammatory response. Harnessing the inflammation response could reduce severity of disease in pandemic or seasonal influenza, particularly in the young, elderly, asthma and COPD patients
Methods: We challenged C57BL/6 mice with Influenza A/NWS/33 (H1N1) virus equivalent to 4.5Log10TCID50 intranasal. Survival, body weight and inflammatory markers were documented in infected mice treated with C-10803, oseltamivir individually or in combination. The drugs were given orally 24 hours post infection.
Results: We observed a significant improvement in survival rates (p<0.01), survival time (p<0.01) and inflammatory markers in the group treated with a combination of oseltamivir and C-10803 when compared to oseltamivir alone. We attribute the benefits in survival in the combination group to the reduction of pro-inflammatory cytokine response elicited subsequent to the viral infection.
Conclusion: Combinations of neuraminidase inhibitors with immunomodulators like C-10803 should be evaluated in clinical trials involving patients with severe influenza e.g. viral exacerbations in asthma & COPD patients. These combinations might also have the potential for the treatment of H5N1 infection as “cytokine storm” is the hallmark of such infections. Combinations of immunomodulators with specifically targeted antivirals should be explored for other viral respiratory infections .

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