Giuseppe
Emeritus
[Source: PLoS ONE, full text: (LINK). Asbtract, edited.]
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A Randomized Clinical Trial of an Inactivated Avian Influenza A (H7N7) Vaccine
Robert B. Couch<SUP>1</SUP><SUP>*</SUP>, Shital M. Patel<SUP>2</SUP>, Chianti L. Wade-Bowers<SUP>1</SUP>, Diane Ni?o<SUP>1</SUP>
<SUP></SUP>
1 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America, 2 Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America
Abstract
Background
Concern for a pandemic caused by a newly emerged avian influenza A virus has led to clinical trials with candidate vaccines as preparation for such an event. Most trials have involved vaccines for influenza A (H5N1), A (H7N7) or A (H9N2).
Objective
To evaluate dosage-related safety and immunogenicity of an inactivated influenza A (H7N7) vaccine in humans.
Design
One hundred twenty-five healthy young adults were randomized to receive two doses intramuscularly of placebo or 7.5, 15, 45 or 90 ?g of HA of an inactivated subunit influenza A (H7N7) vaccine (25 per group), four weeks apart. Reactogenicity was evaluated closely for one week and for any adverse effect for six months after each dose. Serum hemagglutination-inhibiting and neutralizing antibody responses were determined four weeks after each dose and at six months.
Results
Reactogenicity evaluations indicated the vaccinations were well tolerated. Only one subject developed a ≥4-fold serum hemagglutination-inhibition (HAI) antibody response and a final titer of ≥1:40 four weeks after dose two and only five subjects developed a neutralizing antibody rise and a final titer of ≥1:40 in tests performed at a central laboratory. Four of the five were given the 45 or 90 ?g HA dosage. A more sensitive HAI assay at the study site revealed a dose-response with increasing HA dosage but only 36% in the 90 ?g HA group developed a ≥4-fold rise in antibody in this test and only one of these achieved a titer of ≥1:32.
Conclusion
This inactivated subunit influenza A (H7N7) vaccine was safe but poorly immunogenic in humans.
Trials Registration
ClinicalTrials.gov NCT00546585
Citation: Couch RB, Patel SM, Wade-Bowers CL, Ni?o D (2012) A Randomized Clinical Trial of an Inactivated Avian Influenza A (H7N7) Vaccine. PLoS ONE 7(12): e49704. doi:10.1371/journal.pone.0049704
Editor: Eliane Namie Miyaji, Instituto Butantan, Brazil
Received: July 23, 2012; Accepted: October 4, 2012; Published: December 11, 2012
Copyright: ? 2012 Couch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: Research performed by the authors and summarized in this report was supported by Public Health Service Contract NO1 AI 30039 from the National Institute of Allergy and Infectious Diseases. The funders participated in study design but had no role in data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
* E-mail: rcouch@bcm.edu
-Robert B. Couch<SUP>1</SUP><SUP>*</SUP>, Shital M. Patel<SUP>2</SUP>, Chianti L. Wade-Bowers<SUP>1</SUP>, Diane Ni?o<SUP>1</SUP>
<SUP></SUP>
1 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America, 2 Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America
Abstract
Background
Concern for a pandemic caused by a newly emerged avian influenza A virus has led to clinical trials with candidate vaccines as preparation for such an event. Most trials have involved vaccines for influenza A (H5N1), A (H7N7) or A (H9N2).
Objective
To evaluate dosage-related safety and immunogenicity of an inactivated influenza A (H7N7) vaccine in humans.
Design
One hundred twenty-five healthy young adults were randomized to receive two doses intramuscularly of placebo or 7.5, 15, 45 or 90 ?g of HA of an inactivated subunit influenza A (H7N7) vaccine (25 per group), four weeks apart. Reactogenicity was evaluated closely for one week and for any adverse effect for six months after each dose. Serum hemagglutination-inhibiting and neutralizing antibody responses were determined four weeks after each dose and at six months.
Results
Reactogenicity evaluations indicated the vaccinations were well tolerated. Only one subject developed a ≥4-fold serum hemagglutination-inhibition (HAI) antibody response and a final titer of ≥1:40 four weeks after dose two and only five subjects developed a neutralizing antibody rise and a final titer of ≥1:40 in tests performed at a central laboratory. Four of the five were given the 45 or 90 ?g HA dosage. A more sensitive HAI assay at the study site revealed a dose-response with increasing HA dosage but only 36% in the 90 ?g HA group developed a ≥4-fold rise in antibody in this test and only one of these achieved a titer of ≥1:32.
Conclusion
This inactivated subunit influenza A (H7N7) vaccine was safe but poorly immunogenic in humans.
Trials Registration
ClinicalTrials.gov NCT00546585
Citation: Couch RB, Patel SM, Wade-Bowers CL, Ni?o D (2012) A Randomized Clinical Trial of an Inactivated Avian Influenza A (H7N7) Vaccine. PLoS ONE 7(12): e49704. doi:10.1371/journal.pone.0049704
Editor: Eliane Namie Miyaji, Instituto Butantan, Brazil
Received: July 23, 2012; Accepted: October 4, 2012; Published: December 11, 2012
Copyright: ? 2012 Couch et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: Research performed by the authors and summarized in this report was supported by Public Health Service Contract NO1 AI 30039 from the National Institute of Allergy and Infectious Diseases. The funders participated in study design but had no role in data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
* E-mail: rcouch@bcm.edu
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