Towards a universal influenza vaccine: volunteer virus challenge studies in quarantine to speed the development and subsequent licensing
Identifieur interne : 000C75 ( Pmc/Curation ); précédent : 000C74; suivant : 000C76Towards a universal influenza vaccine: volunteer virus challenge studies in quarantine to speed the development and subsequent licensing
Auteurs : John S. OxfordSource :
- British Journal of Clinical Pharmacology [ 0306-5251 ] ; 2013.
Abstract
There are now more than 5 experimental vaccine formulations which induce T and B cell immunity towards the internally situated virus proteins matrix (M1 and M2e) and nucleoprotein (NP), and towards stem and stalk regions of the HA which have a shared antigenic structure amongst many of the 17 influenza A virus sub types. Such ‘universal vaccines’ could be used, at least in theory, as a prophylactic stockpile vaccine for newly emerged epidemic and novel pandemic influenza A viruses or as a supplement to conventional HA/NA vaccines. My own laboratory has approached the problem from the clinical viewpoint by identifying CD4+ cells which are present in influenza infected volunteers who resist influenza infection. We have established precisely which peptides in M and NP proteins react with these immune CD4 cells. These experimental vaccines induce immunity in animal models but with a single exception no data have been published on protection against influenza virus infection in humans. The efficacy of the latter vaccine is based on vaccinia virus (MVA) as a carrier and was analyzed in a quarantine unit. Given the absence of induced HI antibody in the new universal vaccines a possible licensing strategy is a virus challenge model in quarantine whereby healthy volunteers can be immunized with the new vaccine and thereafter deliberately infected and clinical signs recorded alongside quantities of virus excreted and compared with unvaccinated controls.
Url:
DOI: 10.1111/bcp.12146
PubMed: 23617282
PubMed Central: 3731596
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<front><div type="abstract" xml:lang="en"><p>There are now more than 5 experimental vaccine formulations which induce T and B cell immunity towards the internally situated virus proteins matrix (M1 and M2e) and nucleoprotein (NP), and towards stem and stalk regions of the HA which have a shared antigenic structure amongst many of the 17 influenza A virus sub types. Such ‘universal vaccines’ could be used, at least in theory, as a prophylactic stockpile vaccine for newly emerged epidemic and novel pandemic influenza A viruses or as a supplement to conventional HA/NA vaccines. My own laboratory has approached the problem from the clinical viewpoint by identifying CD4<sup>+</sup>
cells which are present in influenza infected volunteers who resist influenza infection. We have established precisely which peptides in M and NP proteins react with these immune CD4 cells. These experimental vaccines induce immunity in animal models but with a single exception no data have been published on protection against influenza virus infection in humans. The efficacy of the latter vaccine is based on vaccinia virus (MVA) as a carrier and was analyzed in a quarantine unit. Given the absence of induced HI antibody in the new universal vaccines a possible licensing strategy is a virus challenge model in quarantine whereby healthy volunteers can be immunized with the new vaccine and thereafter deliberately infected and clinical signs recorded alongside quantities of virus excreted and compared with unvaccinated controls.</p>
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<pmc article-type="review-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Br J Clin Pharmacol</journal-id>
<journal-id journal-id-type="iso-abbrev">Br J Clin Pharmacol</journal-id>
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<title-group><article-title>Towards a universal influenza vaccine: volunteer virus challenge studies in quarantine to speed the development and subsequent licensing</article-title>
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<contrib-group><contrib contrib-type="author"><name><surname>Oxford</surname>
<given-names>John S</given-names>
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<aff><institution>Blizard Institute of Cell and Molecular Science, Bart's and the London and Retroscreen Virology Ltd, Queen Mary's BioEnterprises, Innovation Centre</institution>
<addr-line>London, E1 2AX, UK</addr-line>
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<author-notes><corresp id="cor1">Professor John Oxford, Retroscreen Virology, Queen Mary, BioEnterprises, Innovation Centre, 42 New Road, London E1 2AX, UK. Tel.: +0207-756-1300 Fax: +0203-070-0086 E-mail: <email>j.oxford@retroscreen.com</email>
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<pub-date pub-type="ppub"><month>8</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub"><day>25</day>
<month>4</month>
<year>2013</year>
</pub-date>
<volume>76</volume>
<issue>2</issue>
<fpage>210</fpage>
<lpage>216</lpage>
<history><date date-type="received"><day>08</day>
<month>10</month>
<year>2012</year>
</date>
<date date-type="accepted"><day>22</day>
<month>3</month>
<year>2013</year>
</date>
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<permissions><copyright-statement>Copyright © 2013 The British Pharmacological Society</copyright-statement>
<copyright-year>2013</copyright-year>
</permissions>
<abstract><p>There are now more than 5 experimental vaccine formulations which induce T and B cell immunity towards the internally situated virus proteins matrix (M1 and M2e) and nucleoprotein (NP), and towards stem and stalk regions of the HA which have a shared antigenic structure amongst many of the 17 influenza A virus sub types. Such ‘universal vaccines’ could be used, at least in theory, as a prophylactic stockpile vaccine for newly emerged epidemic and novel pandemic influenza A viruses or as a supplement to conventional HA/NA vaccines. My own laboratory has approached the problem from the clinical viewpoint by identifying CD4<sup>+</sup>
cells which are present in influenza infected volunteers who resist influenza infection. We have established precisely which peptides in M and NP proteins react with these immune CD4 cells. These experimental vaccines induce immunity in animal models but with a single exception no data have been published on protection against influenza virus infection in humans. The efficacy of the latter vaccine is based on vaccinia virus (MVA) as a carrier and was analyzed in a quarantine unit. Given the absence of induced HI antibody in the new universal vaccines a possible licensing strategy is a virus challenge model in quarantine whereby healthy volunteers can be immunized with the new vaccine and thereafter deliberately infected and clinical signs recorded alongside quantities of virus excreted and compared with unvaccinated controls.</p>
</abstract>
<kwd-group><kwd>influenza</kwd>
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<kwd>human volunteers</kwd>
<kwd>matrix</kwd>
<kwd>quarantine</kwd>
<kwd>universal vaccine</kwd>
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