Giuseppe
Emeritus
[Source: PLoS ONE, full page: (LINK). Abstract, edited.]
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Evaluations for In Vitro Correlates of Immunogenicity of Inactivated Influenza A H5, H7 and H9 Vaccines in Humans
Robert B. Couch<SUP>1</SUP><SUP>*</SUP>, William K. Decker<SUP>2</SUP>, Budi Utama<SUP>1</SUP>, Robert L. Atmar<SUP>1</SUP><SUP>,</SUP><SUP>3</SUP>, Diane Ni?o<SUP>1</SUP>, Jing Qi Feng<SUP>4</SUP>, Matthew M. Halpert<SUP>2</SUP>, Gillian M. Air<SUP>4</SUP>
<SUP></SUP>
1 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America, 2 Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America, 3 Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America, 4 Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
Abstract
Background
Serum antibody responses in humans to inactivated influenza A (H5N1), (H9N2) and A (H7) vaccines have been varied but frequently low, particularly for subunit vaccines without adjuvant despite hemagglutinin (HA) concentrations expected to induce good responses.
Design
To help understand the low responses to subunit vaccines, we evaluated influenza A (H5N1), (H9N2), (H7N7) vaccines and 2009 pandemic (H1N1) vaccines for antigen uptake, processing and presentation by dendritic cells to T cells, conformation of vaccine HA in antibody binding assays and gel analyses, HA titers with different red blood cells, and vaccine morphology in electron micrographs (EM).
Results
Antigen uptake, processing and presentation of H5, H7, H9 and H1 vaccine preparations evaluated in humans appeared normal. No differences were detected in antibody interactions with vaccine and matched virus; although H7 trimer was not detected in western blots, no abnormalities in the conformation of the HA antigens were identified. The lowest HA titers for the vaccines were <1:4 for the H7 vaccine and 1:661 for an H9 vaccine; these vaccines induced the fewest antibody responses. A (H1N1) vaccines were the most immunogenic in humans; intact virus and virus pieces were prominent in EM. A good immunogenic A (H9N2) vaccine contained primarily particles of viral membrane with external HA and NA. A (H5N1) vaccines intermediate in immunogenicity were mostly indistinct structural units with stellates; the least immunogenic A (H7N7) vaccine contained mostly small 5 to 20 nm structures.
Summary
Antigen uptake, processing and presentation to human T cells and conformation of the HA appeared normal for each inactivated influenza A vaccine. Low HA titer was associated with low immunogenicity and presence of particles or split virus pieces was associated with higher immunogenicity.
Citation: Couch RB, Decker WK, Utama B, Atmar RL, Ni?o D, et al. (2012) Evaluations for In Vitro Correlates of Immunogenicity of Inactivated Influenza A H5, H7 and H9 Vaccines in Humans. PLoS ONE 7(12): e50830. doi:10.1371/journal.pone.0050830
Editor: Eliane Namie Miyaji, Instituto Butantan, Brazil
Received: July 19, 2012; Accepted: October 24, 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 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. The funders did not participate in study design and 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.
* E-mail: rcouch@bcm.edu
-Robert B. Couch<SUP>1</SUP><SUP>*</SUP>, William K. Decker<SUP>2</SUP>, Budi Utama<SUP>1</SUP>, Robert L. Atmar<SUP>1</SUP><SUP>,</SUP><SUP>3</SUP>, Diane Ni?o<SUP>1</SUP>, Jing Qi Feng<SUP>4</SUP>, Matthew M. Halpert<SUP>2</SUP>, Gillian M. Air<SUP>4</SUP>
<SUP></SUP>
1 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America, 2 Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, United States of America, 3 Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America, 4 Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America
Abstract
Background
Serum antibody responses in humans to inactivated influenza A (H5N1), (H9N2) and A (H7) vaccines have been varied but frequently low, particularly for subunit vaccines without adjuvant despite hemagglutinin (HA) concentrations expected to induce good responses.
Design
To help understand the low responses to subunit vaccines, we evaluated influenza A (H5N1), (H9N2), (H7N7) vaccines and 2009 pandemic (H1N1) vaccines for antigen uptake, processing and presentation by dendritic cells to T cells, conformation of vaccine HA in antibody binding assays and gel analyses, HA titers with different red blood cells, and vaccine morphology in electron micrographs (EM).
Results
Antigen uptake, processing and presentation of H5, H7, H9 and H1 vaccine preparations evaluated in humans appeared normal. No differences were detected in antibody interactions with vaccine and matched virus; although H7 trimer was not detected in western blots, no abnormalities in the conformation of the HA antigens were identified. The lowest HA titers for the vaccines were <1:4 for the H7 vaccine and 1:661 for an H9 vaccine; these vaccines induced the fewest antibody responses. A (H1N1) vaccines were the most immunogenic in humans; intact virus and virus pieces were prominent in EM. A good immunogenic A (H9N2) vaccine contained primarily particles of viral membrane with external HA and NA. A (H5N1) vaccines intermediate in immunogenicity were mostly indistinct structural units with stellates; the least immunogenic A (H7N7) vaccine contained mostly small 5 to 20 nm structures.
Summary
Antigen uptake, processing and presentation to human T cells and conformation of the HA appeared normal for each inactivated influenza A vaccine. Low HA titer was associated with low immunogenicity and presence of particles or split virus pieces was associated with higher immunogenicity.
Citation: Couch RB, Decker WK, Utama B, Atmar RL, Ni?o D, et al. (2012) Evaluations for In Vitro Correlates of Immunogenicity of Inactivated Influenza A H5, H7 and H9 Vaccines in Humans. PLoS ONE 7(12): e50830. doi:10.1371/journal.pone.0050830
Editor: Eliane Namie Miyaji, Instituto Butantan, Brazil
Received: July 19, 2012; Accepted: October 24, 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 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. The funders did not participate in study design and 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.
* E-mail: rcouch@bcm.edu
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