Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stability

<p>Abstract</p> <p>Background</p> <p>The recent H1N1 influenza pandemic illustrated the shortcomings of the vaccine manufacturing process. The A/California/07/2009 H1N1 pandemic influenza vaccine or A(H1N1)pdm09 was available late and in short supply as a result of dela...

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Main Authors: Feshchenko Elena, Rhodes David G, Felberbaum Rachael, McPherson Clifton, Rininger Joseph A, Post Penny, Cox Manon MJ
Format: Article
Language:English
Published: BMC 2012-10-01
Series:BMC Biotechnology
Subjects:
Online Access:http://www.biomedcentral.com/1472-6750/12/77
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author Feshchenko Elena
Rhodes David G
Felberbaum Rachael
McPherson Clifton
Rininger Joseph A
Post Penny
Cox Manon MJ
author_facet Feshchenko Elena
Rhodes David G
Felberbaum Rachael
McPherson Clifton
Rininger Joseph A
Post Penny
Cox Manon MJ
author_sort Feshchenko Elena
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>The recent H1N1 influenza pandemic illustrated the shortcomings of the vaccine manufacturing process. The A/California/07/2009 H1N1 pandemic influenza vaccine or A(H1N1)pdm09 was available late and in short supply as a result of delays in production caused by low yields and poor antigen stability. Recombinant technology offers the opportunity to shorten manufacturing time. A trivalent recombinant hemagglutinin (rHA) vaccine candidate for seasonal influenza produced using the baculovirus expression vector system (BEVS) was shown to be as effective and safe as egg-derived trivalent inactivated vaccine (TIV) in human clinical studies. In this study, we describe the characterization of the A/California/07/2009 rHA protein and compare the H1N1 pandemic rHA to other seasonal rHA proteins.</p> <p>Results</p> <p>Our data show that, like other rHA proteins, purified A/California/07/2009 rHA forms multimeric rosette-like particles of 20–40 nm that are biologically active and immunogenic in mice as assayed by hemagglutination inhibition (HAI) antibody titers. However, proteolytic digest analysis revealed that A/California/07/2009 rHA is more susceptible to proteolytic degradation than rHA proteins derived from other seasonal influenza viruses. We identified a specific proteolytic site conserved across multiple hemagglutinin (HA) proteins that is likely more accessible in A/California/07/2009 HA, possibly as a result of differences in its protein structure, and may contribute to lower antigen stability.</p> <p>Conclusion</p> <p>We conclude that, similar to the recombinant seasonal influenza vaccine, recombinant A(H1N1)pdm09 vaccine is likely to perform comparably to licensed A(H1N1)pdm09 vaccines and could offer manufacturing advantages.</p>
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spelling doaj.art-e806fcc724714f20b68f0061c36d81312022-12-22T03:00:25ZengBMCBMC Biotechnology1472-67502012-10-011217710.1186/1472-6750-12-77Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stabilityFeshchenko ElenaRhodes David GFelberbaum RachaelMcPherson CliftonRininger Joseph APost PennyCox Manon MJ<p>Abstract</p> <p>Background</p> <p>The recent H1N1 influenza pandemic illustrated the shortcomings of the vaccine manufacturing process. The A/California/07/2009 H1N1 pandemic influenza vaccine or A(H1N1)pdm09 was available late and in short supply as a result of delays in production caused by low yields and poor antigen stability. Recombinant technology offers the opportunity to shorten manufacturing time. A trivalent recombinant hemagglutinin (rHA) vaccine candidate for seasonal influenza produced using the baculovirus expression vector system (BEVS) was shown to be as effective and safe as egg-derived trivalent inactivated vaccine (TIV) in human clinical studies. In this study, we describe the characterization of the A/California/07/2009 rHA protein and compare the H1N1 pandemic rHA to other seasonal rHA proteins.</p> <p>Results</p> <p>Our data show that, like other rHA proteins, purified A/California/07/2009 rHA forms multimeric rosette-like particles of 20–40 nm that are biologically active and immunogenic in mice as assayed by hemagglutination inhibition (HAI) antibody titers. However, proteolytic digest analysis revealed that A/California/07/2009 rHA is more susceptible to proteolytic degradation than rHA proteins derived from other seasonal influenza viruses. We identified a specific proteolytic site conserved across multiple hemagglutinin (HA) proteins that is likely more accessible in A/California/07/2009 HA, possibly as a result of differences in its protein structure, and may contribute to lower antigen stability.</p> <p>Conclusion</p> <p>We conclude that, similar to the recombinant seasonal influenza vaccine, recombinant A(H1N1)pdm09 vaccine is likely to perform comparably to licensed A(H1N1)pdm09 vaccines and could offer manufacturing advantages.</p>http://www.biomedcentral.com/1472-6750/12/77Recombinant hemagglutininInfluenza pandemic vaccineH1N1Baculovirus expression vector system (BEVS)FlublokA(H1N1)pdm09
spellingShingle Feshchenko Elena
Rhodes David G
Felberbaum Rachael
McPherson Clifton
Rininger Joseph A
Post Penny
Cox Manon MJ
Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stability
BMC Biotechnology
Recombinant hemagglutinin
Influenza pandemic vaccine
H1N1
Baculovirus expression vector system (BEVS)
Flublok
A(H1N1)pdm09
title Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stability
title_full Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stability
title_fullStr Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stability
title_full_unstemmed Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stability
title_short Pandemic influenza vaccine: characterization of A/California/07/2009 (H1N1) recombinant hemagglutinin protein and insights into H1N1 antigen stability
title_sort pandemic influenza vaccine characterization of a california 07 2009 h1n1 recombinant hemagglutinin protein and insights into h1n1 antigen stability
topic Recombinant hemagglutinin
Influenza pandemic vaccine
H1N1
Baculovirus expression vector system (BEVS)
Flublok
A(H1N1)pdm09
url http://www.biomedcentral.com/1472-6750/12/77
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