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...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2012-10-01
|
Series: | BMC Biotechnology |
Subjects: | |
Online Access: | http://www.biomedcentral.com/1472-6750/12/77 |
_version_ | 1811295384305139712 |
---|---|
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> |
first_indexed | 2024-04-13T05:31:40Z |
format | Article |
id | doaj.art-e806fcc724714f20b68f0061c36d8131 |
institution | Directory Open Access Journal |
issn | 1472-6750 |
language | English |
last_indexed | 2024-04-13T05:31:40Z |
publishDate | 2012-10-01 |
publisher | BMC |
record_format | Article |
series | BMC Biotechnology |
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 |
work_keys_str_mv | AT feshchenkoelena pandemicinfluenzavaccinecharacterizationofacalifornia072009h1n1recombinanthemagglutininproteinandinsightsintoh1n1antigenstability AT rhodesdavidg pandemicinfluenzavaccinecharacterizationofacalifornia072009h1n1recombinanthemagglutininproteinandinsightsintoh1n1antigenstability AT felberbaumrachael pandemicinfluenzavaccinecharacterizationofacalifornia072009h1n1recombinanthemagglutininproteinandinsightsintoh1n1antigenstability AT mcphersonclifton pandemicinfluenzavaccinecharacterizationofacalifornia072009h1n1recombinanthemagglutininproteinandinsightsintoh1n1antigenstability AT riningerjosepha pandemicinfluenzavaccinecharacterizationofacalifornia072009h1n1recombinanthemagglutininproteinandinsightsintoh1n1antigenstability AT postpenny pandemicinfluenzavaccinecharacterizationofacalifornia072009h1n1recombinanthemagglutininproteinandinsightsintoh1n1antigenstability AT coxmanonmj pandemicinfluenzavaccinecharacterizationofacalifornia072009h1n1recombinanthemagglutininproteinandinsightsintoh1n1antigenstability |