tetano
Editor, Senior Moderator
Clin Infect Dis. 2014 Nov 20. pii: ciu924. [Epub ahead of print]
Validation of a Wild-Type Influenza A Human Challenge Model: H1N1pdMIST, An A(H1N1)pdm09 Dose Finding IND Study.
Memoli MJ1, Czajkowski L2, Reed S2, Athota R2, Bristol T2, Proudfoot K2, Fargis S2, Stein M2, Dunfee RL2, Shaw PA3, Davey RT4, Taubenberger JK2.
Author information
Abstract
BACKGROUND:
Healthy volunteer wild-type influenza challenge models offer a unique opportunity to evaluate multiple aspects of this important virus. Such studies have not been performed in the U.S. in over a decade, limiting our capability to investigate this virus and develop countermeasures. We have completed the first ever wild-type influenza A challenge study under an IND. This dose finding study will lead to further development of this model both for A(H1N1)pdm09 and other strains of influenza.
METHODS:
Volunteers were admitted to an isolation unit at the NIH Clinical Center for a minimum of 9 days. A reverse genetics, cell-based, GMP produced, wild-type A(H1N1)pdm09 virus was administered intranasally. Escalating doses were given until a dose was reached that produced disease in a minimum of 60% of volunteers.
RESULTS:
An optimal dose of 107 TCID50 was reached which caused mild to moderate influenza disease in 69% of individuals with mean viral shedding for 4-5 days and significant rises in convalescent influenza antibody titers. Viral shedding preceded symptoms by 12-24 hours and terminated 2-3 days prior to symptom resolution, indicating that individuals may be infectious before symptom development. As expected nasal congestion and rhinorrhea were most common, but interestingly, fever was observed in only 10%.
CONCLUSION:
This study represents the first healthy volunteer influenza challenge model using a GMP-produced wild-type virus under an IND. This unique clinical research program will facilitate future studies of influenza pathogenesis, animal model validation, and the rapid, efficient, and cost-effective evaluation of efficacy of novel vaccines and therapeutics.
Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
PMID:
25416753
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25416753
Validation of a Wild-Type Influenza A Human Challenge Model: H1N1pdMIST, An A(H1N1)pdm09 Dose Finding IND Study.
Memoli MJ1, Czajkowski L2, Reed S2, Athota R2, Bristol T2, Proudfoot K2, Fargis S2, Stein M2, Dunfee RL2, Shaw PA3, Davey RT4, Taubenberger JK2.
Author information
Abstract
BACKGROUND:
Healthy volunteer wild-type influenza challenge models offer a unique opportunity to evaluate multiple aspects of this important virus. Such studies have not been performed in the U.S. in over a decade, limiting our capability to investigate this virus and develop countermeasures. We have completed the first ever wild-type influenza A challenge study under an IND. This dose finding study will lead to further development of this model both for A(H1N1)pdm09 and other strains of influenza.
METHODS:
Volunteers were admitted to an isolation unit at the NIH Clinical Center for a minimum of 9 days. A reverse genetics, cell-based, GMP produced, wild-type A(H1N1)pdm09 virus was administered intranasally. Escalating doses were given until a dose was reached that produced disease in a minimum of 60% of volunteers.
RESULTS:
An optimal dose of 107 TCID50 was reached which caused mild to moderate influenza disease in 69% of individuals with mean viral shedding for 4-5 days and significant rises in convalescent influenza antibody titers. Viral shedding preceded symptoms by 12-24 hours and terminated 2-3 days prior to symptom resolution, indicating that individuals may be infectious before symptom development. As expected nasal congestion and rhinorrhea were most common, but interestingly, fever was observed in only 10%.
CONCLUSION:
This study represents the first healthy volunteer influenza challenge model using a GMP-produced wild-type virus under an IND. This unique clinical research program will facilitate future studies of influenza pathogenesis, animal model validation, and the rapid, efficient, and cost-effective evaluation of efficacy of novel vaccines and therapeutics.
Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.
PMID:
25416753
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25416753