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Comparison of a novel microcrystalline tyrosine adjuvant with aluminium hydroxide for enhancing vaccination against seasonal influenza

Identifieur interne : 000193 ( Pmc/Curation ); précédent : 000192; suivant : 000194

Comparison of a novel microcrystalline tyrosine adjuvant with aluminium hydroxide for enhancing vaccination against seasonal influenza

Auteurs : M. D. Heath ; N. J. Swan ; A. C. Marriott ; N. J. Silman ; B. Hallis ; C. Prevosto ; K. E. Gooch ; M. A. Skinner

Source :

RBID : PMC:5369220

Abstract

Background

Vaccination against seasonal influenza strains is recommended for “high risk” patient groups such as infants, elderly and those with respiratory or circulatory diseases. However, efficacy of the trivalent influenza vaccine (TIV) is poor in many cases and in the event of an influenza pandemic, mono-valent vaccines have been rapidly developed and deployed. One of the main issues with use of vaccine in pandemic situations is the lack of a suitable quantity of vaccine early enough during the pandemic to exert a major influence on the transmission of virus and disease outcome. One approach is to use a dose-sparing regimen which inevitably involves enhancing the efficacy using adjuvants.

Methods

In this study we compare the use of a novel microcrystalline tyrosine (MCT) adjuvant, which is currently used in a niche area of allergy immunotherapy, for its ability to enhance the efficacy of a seasonal TIV preparation. The efficacy of the MCT adjuvant formulation was compared to alum adjuvanted TIV and to TIV administered without adjuvant using a ferret challenge model to determine vaccine efficacy.

Results

The MCT was found to possess high protein-binding capacity. In the two groups where TIV was formulated with adjuvant, the immune response was found to be higher (as determined by HAI titre) than vaccine administered without adjuvant and especially so after challenge with a live influenza virus. Vaccinated animals exhibited lower viral loads (as determined using RT-PCR) than control animals where no vaccine was administered.

Conclusions

The attributes of each adjuvant in stimulating single-dose protection against a poorly immunogenic vaccine was demonstrated. The properties of MCT that lead to the reported effectiveness warrants further exploration in this and other vaccine targets - particularly where appropriate immunogenic, biodegradable and stable alternative adjuvants are sought.

Electronic supplementary material

The online version of this article (doi:10.1186/s12879-017-2329-5) contains supplementary material, which is available to authorized users.


Url:
DOI: 10.1186/s12879-017-2329-5
PubMed: 28347293
PubMed Central: 5369220

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M. D. Heath
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N. J. Swan
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A. C. Marriott
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N. J. Silman
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B. Hallis
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C. Prevosto
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K. E. Gooch
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M. A. Skinner
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<title>Background</title>
<p>Vaccination against seasonal influenza strains is recommended for “high risk” patient groups such as infants, elderly and those with respiratory or circulatory diseases. However, efficacy of the trivalent influenza vaccine (TIV) is poor in many cases and in the event of an influenza pandemic, mono-valent vaccines have been rapidly developed and deployed. One of the main issues with use of vaccine in pandemic situations is the lack of a suitable quantity of vaccine early enough during the pandemic to exert a major influence on the transmission of virus and disease outcome. One approach is to use a dose-sparing regimen which inevitably involves enhancing the efficacy using adjuvants.</p>
</sec>
<sec>
<title>Methods</title>
<p>In this study we compare the use of a novel microcrystalline tyrosine (MCT) adjuvant, which is currently used in a niche area of allergy immunotherapy, for its ability to enhance the efficacy of a seasonal TIV preparation. The efficacy of the MCT adjuvant formulation was compared to alum adjuvanted TIV and to TIV administered without adjuvant using a ferret challenge model to determine vaccine efficacy.</p>
</sec>
<sec>
<title>Results</title>
<p>The MCT was found to possess high protein-binding capacity. In the two groups where TIV was formulated with adjuvant, the immune response was found to be higher (as determined by HAI titre) than vaccine administered without adjuvant and especially so after challenge with a live influenza virus. Vaccinated animals exhibited lower viral loads (as determined using RT-PCR) than control animals where no vaccine was administered.</p>
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<sec>
<title>Conclusions</title>
<p>The attributes of each adjuvant in stimulating single-dose protection against a poorly immunogenic vaccine was demonstrated. The properties of MCT that lead to the reported effectiveness warrants further exploration in this and other vaccine targets - particularly where appropriate immunogenic, biodegradable and stable alternative adjuvants are sought.</p>
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<p>The online version of this article (doi:10.1186/s12879-017-2329-5) contains supplementary material, which is available to authorized users.</p>
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<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">BMC Infect Dis</journal-id>
<journal-id journal-id-type="iso-abbrev">BMC Infect. Dis</journal-id>
<journal-title-group>
<journal-title>BMC Infectious Diseases</journal-title>
</journal-title-group>
<issn pub-type="epub">1471-2334</issn>
<publisher>
<publisher-name>BioMed Central</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">28347293</article-id>
<article-id pub-id-type="pmc">5369220</article-id>
<article-id pub-id-type="publisher-id">2329</article-id>
<article-id pub-id-type="doi">10.1186/s12879-017-2329-5</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Comparison of a novel microcrystalline tyrosine adjuvant with aluminium hydroxide for enhancing vaccination against seasonal influenza</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Heath</surname>
<given-names>M. D</given-names>
</name>
<address>
<email>matthew.heath@allergytherapeutics.com</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Swan</surname>
<given-names>N. J.</given-names>
</name>
<address>
<email>Nicola.swan@allergytherapeutics.com</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Marriott</surname>
<given-names>A. C.</given-names>
</name>
<address>
<email>Anthony.marriott@phe.gov.uk</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Silman</surname>
<given-names>N. J.</given-names>
</name>
<address>
<email>nigel.silman@phe.gov.uk</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hallis</surname>
<given-names>B.</given-names>
</name>
<address>
<email>bassam.hallis@phe.gov.uk</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Prevosto</surname>
<given-names>C.</given-names>
</name>
<address>
<email>Claudia.provosto@phe.gov.uk</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Gooch</surname>
<given-names>K. E.</given-names>
</name>
<address>
<email>Karen.gooch@phe.gov.uk</email>
</address>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Skinner</surname>
<given-names>M. A.</given-names>
</name>
<address>
<email>murray.skinner@allergytherapeutics.com</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
</contrib>
<aff id="Aff1">
<label>1</label>
Allergy Therapeutics Ltd, Dominion Way, West Sussex, BN14 8SA UK</aff>
<aff id="Aff2">
<label>2</label>
<institution-wrap>
<institution-id institution-id-type="ISNI">0000 0000 9421 9783</institution-id>
<institution-id institution-id-type="GRID">grid.271308.f</institution-id>
<institution></institution>
<institution>Public Health England, PHE Porton,</institution>
</institution-wrap>
Porton Down, Salisbury, SP4 0JG UK</aff>
<aff id="Aff3">
<label>3</label>
Present address: Kings College, Guys Campus, London, SE1 3QD UK</aff>
</contrib-group>
<pub-date pub-type="epub">
<day>27</day>
<month>3</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>27</day>
<month>3</month>
<year>2017</year>
</pub-date>
<pub-date pub-type="collection">
<year>2017</year>
</pub-date>
<volume>17</volume>
<elocation-id>232</elocation-id>
<history>
<date date-type="received">
<day>9</day>
<month>3</month>
<year>2016</year>
</date>
<date date-type="accepted">
<day>17</day>
<month>3</month>
<year>2017</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author(s). 2017</copyright-statement>
<license license-type="OpenAccess">
<license-p>
<bold>Open Access</bold>
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>
) applies to the data made available in this article, unless otherwise stated.</license-p>
</license>
</permissions>
<abstract id="Abs1">
<sec>
<title>Background</title>
<p>Vaccination against seasonal influenza strains is recommended for “high risk” patient groups such as infants, elderly and those with respiratory or circulatory diseases. However, efficacy of the trivalent influenza vaccine (TIV) is poor in many cases and in the event of an influenza pandemic, mono-valent vaccines have been rapidly developed and deployed. One of the main issues with use of vaccine in pandemic situations is the lack of a suitable quantity of vaccine early enough during the pandemic to exert a major influence on the transmission of virus and disease outcome. One approach is to use a dose-sparing regimen which inevitably involves enhancing the efficacy using adjuvants.</p>
</sec>
<sec>
<title>Methods</title>
<p>In this study we compare the use of a novel microcrystalline tyrosine (MCT) adjuvant, which is currently used in a niche area of allergy immunotherapy, for its ability to enhance the efficacy of a seasonal TIV preparation. The efficacy of the MCT adjuvant formulation was compared to alum adjuvanted TIV and to TIV administered without adjuvant using a ferret challenge model to determine vaccine efficacy.</p>
</sec>
<sec>
<title>Results</title>
<p>The MCT was found to possess high protein-binding capacity. In the two groups where TIV was formulated with adjuvant, the immune response was found to be higher (as determined by HAI titre) than vaccine administered without adjuvant and especially so after challenge with a live influenza virus. Vaccinated animals exhibited lower viral loads (as determined using RT-PCR) than control animals where no vaccine was administered.</p>
</sec>
<sec>
<title>Conclusions</title>
<p>The attributes of each adjuvant in stimulating single-dose protection against a poorly immunogenic vaccine was demonstrated. The properties of MCT that lead to the reported effectiveness warrants further exploration in this and other vaccine targets - particularly where appropriate immunogenic, biodegradable and stable alternative adjuvants are sought.</p>
</sec>
<sec>
<title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s12879-017-2329-5) contains supplementary material, which is available to authorized users.</p>
</sec>
</abstract>
<kwd-group xml:lang="en">
<title>Keywords</title>
<kwd>Vaccine</kwd>
<kwd>Influenza</kwd>
<kwd>Adjuvant</kwd>
<kwd>Microcrystalline tyrosine</kwd>
<kwd>Aluminum</kwd>
<kwd>Ferret</kwd>
</kwd-group>
<custom-meta-group>
<custom-meta>
<meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2017</meta-value>
</custom-meta>
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