tetano
Editor, Senior Moderator
J Infect Dis. 2014 Oct 3. pii: jiu539. [Epub ahead of print]
Efficacy and Safety of Treatment with an Anti-M2e Monoclonal Antibody in Experimental Human Influenza.
Ramos EL1, Mitcham JL1, Koller TD1, Bonavia A1, Usner DW2, Balaratnam G3, Fredlund P1, Swiderek KM1.
Author information
Abstract
BACKGROUND:
The efficacy of TCN-032, a human mAb targeting a conserved epitope on M2e, was explored in experimental human influenza.
METHODS:
Healthy volunteers were inoculated with influenza A/Wisconsin/67/2005 (H3N2) and received single dose of study drug, TCN-032 or placebo 24 hours later. Subjects were monitored for symptoms, viral shedding and safety, including cytokine measurements. Oseltamivir was administered 7 days after inoculation.
RESULTS:
While the primary objective of reducing the proportion of subjects developing any Grade 2 or greater influenza symptom, or pyrexia, was not achieved, TCN-032-treated subjects showed 35% reduction (p=0.047) in median total symptom AUC (Days 1-7) and 2.2 log reduction in median viral load AUC (Days 2-7) by qPCR (p=0.095) compared to placebo subjects. TCN-032 was safe and well tolerated with no additional safety signals following administration of oseltamivir. Serum cytokine levels (IFN-γ, TNF-α, IL-8, IL-10) were similar in both groups. Genotypic and phenotypic analyses showed no difference between virus derived from subjects after TCN-032 treatment and parental strain.
CONCLUSIONS:
These data support that TCN-032 may provide immediate immunity and therapeutic benefit in influenza A infection, with no apparent emergence of resistant virus. TCN-032 was safe with no evidence of immune exacerbation based on serum cytokine expression.
? The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
PMID:
25281755
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25281755
Efficacy and Safety of Treatment with an Anti-M2e Monoclonal Antibody in Experimental Human Influenza.
Ramos EL1, Mitcham JL1, Koller TD1, Bonavia A1, Usner DW2, Balaratnam G3, Fredlund P1, Swiderek KM1.
Author information
Abstract
BACKGROUND:
The efficacy of TCN-032, a human mAb targeting a conserved epitope on M2e, was explored in experimental human influenza.
METHODS:
Healthy volunteers were inoculated with influenza A/Wisconsin/67/2005 (H3N2) and received single dose of study drug, TCN-032 or placebo 24 hours later. Subjects were monitored for symptoms, viral shedding and safety, including cytokine measurements. Oseltamivir was administered 7 days after inoculation.
RESULTS:
While the primary objective of reducing the proportion of subjects developing any Grade 2 or greater influenza symptom, or pyrexia, was not achieved, TCN-032-treated subjects showed 35% reduction (p=0.047) in median total symptom AUC (Days 1-7) and 2.2 log reduction in median viral load AUC (Days 2-7) by qPCR (p=0.095) compared to placebo subjects. TCN-032 was safe and well tolerated with no additional safety signals following administration of oseltamivir. Serum cytokine levels (IFN-γ, TNF-α, IL-8, IL-10) were similar in both groups. Genotypic and phenotypic analyses showed no difference between virus derived from subjects after TCN-032 treatment and parental strain.
CONCLUSIONS:
These data support that TCN-032 may provide immediate immunity and therapeutic benefit in influenza A infection, with no apparent emergence of resistant virus. TCN-032 was safe with no evidence of immune exacerbation based on serum cytokine expression.
? The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
PMID:
25281755
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25281755