Serveur d'exploration H2N2

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Changes in heterosubtypic antibody responses during the first year of the 2009 A(H1N1) influenza pandemic

Identifieur interne : 000102 ( Pmc/Curation ); précédent : 000101; suivant : 000103

Changes in heterosubtypic antibody responses during the first year of the 2009 A(H1N1) influenza pandemic

Auteurs : Gudrun S. Freidl ; Henk-Jan Van Den Ham ; Maciej F. Boni [Viêt Nam, Royaume-Uni] ; Erwin De Bruin ; Marion P. G. Koopmans

Source :

RBID : PMC:4745054

Abstract

Seropositivity to avian influenza (AI) via low-level antibody titers has been reported in the general population and poultry-exposed individuals, raising the question whether these findings reflect true infection with AI or cross-reactivity. Here we investigated serological profiles against human and avian influenza viruses in the general population using a protein microarray platform. We hypothesized that higher antibody diversity across recent H1 and H3 influenza viruses would be associated with heterosubtypic reactivity to older pandemic- and AI viruses. We found significant heterogeneity in antibody profiles. Increased antibody diversity to seasonal influenza viruses was associated with low-level heterosubtypic antibodies to H9 and H7, but not to H5 AI virus. Individuals exposed to the recent 2009 A(H1N1) pandemic showed higher heterosubtypic reactivity. We show that there is a complex interplay between prior exposures to seasonal and recent pandemic influenza viruses and the development of heterosubtypic antibody reactivity to animal influenza viruses.


Url:
DOI: 10.1038/srep20385
PubMed: 26853924
PubMed Central: 4745054

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PMC:4745054

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Gudrun S. Freidl
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Gudrun S. Freidl
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Henk-Jan Van Den Ham
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Erwin De Bruin
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Erwin De Bruin
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Marion P. G. Koopmans
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<p>Seropositivity to avian influenza (AI) via low-level antibody titers has been reported in the general population and poultry-exposed individuals, raising the question whether these findings reflect true infection with AI or cross-reactivity. Here we investigated serological profiles against human and avian influenza viruses in the general population using a protein microarray platform. We hypothesized that higher antibody diversity across recent H1 and H3 influenza viruses would be associated with heterosubtypic reactivity to older pandemic- and AI viruses. We found significant heterogeneity in antibody profiles. Increased antibody diversity to seasonal influenza viruses was associated with low-level heterosubtypic antibodies to H9 and H7, but not to H5 AI virus. Individuals exposed to the recent 2009 A(H1N1) pandemic showed higher heterosubtypic reactivity. We show that there is a complex interplay between prior exposures to seasonal and recent pandemic influenza viruses and the development of heterosubtypic antibody reactivity to animal influenza viruses.</p>
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</back>
</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Sci Rep</journal-id>
<journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id>
<journal-title-group>
<journal-title>Scientific Reports</journal-title>
</journal-title-group>
<issn pub-type="epub">2045-2322</issn>
<publisher>
<publisher-name>Nature Publishing Group</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">26853924</article-id>
<article-id pub-id-type="pmc">4745054</article-id>
<article-id pub-id-type="pii">srep20385</article-id>
<article-id pub-id-type="doi">10.1038/srep20385</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Changes in heterosubtypic antibody responses during the first year of the 2009 A(H1N1) influenza pandemic</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Freidl</surname>
<given-names>Gudrun S.</given-names>
</name>
<xref ref-type="corresp" rid="c1">a</xref>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>van den Ham</surname>
<given-names>Henk-Jan</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Boni</surname>
<given-names>Maciej F.</given-names>
</name>
<xref ref-type="aff" rid="a3">3</xref>
<xref ref-type="aff" rid="a4">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>de Bruin</surname>
<given-names>Erwin</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Koopmans</surname>
<given-names>Marion P.G.</given-names>
</name>
<xref ref-type="aff" rid="a1">1</xref>
<xref ref-type="aff" rid="a2">2</xref>
</contrib>
<aff id="a1">
<label>1</label>
<institution>Viroscience Department, Erasmus Medical Center</institution>
, Rotterdam,
<country>the Netherlands</country>
</aff>
<aff id="a2">
<label>2</label>
<institution>Virology Department, Centre for Infectious Diseases Research, Diagnostics and Screening, National Institute for Public Health and the Environment</institution>
, Bilthoven,
<country>the Netherlands</country>
</aff>
<aff id="a3">
<label>3</label>
<institution>Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Programme</institution>
, Ho Chi Minh City,
<country>Vietnam</country>
</aff>
<aff id="a4">
<label>4</label>
<institution>Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford</institution>
, Oxford,
<country>UK</country>
</aff>
</contrib-group>
<author-notes>
<corresp id="c1">
<label>a</label>
<email>gudrun.freidl@rivm.nl</email>
</corresp>
</author-notes>
<pub-date pub-type="epub">
<day>08</day>
<month>02</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="collection">
<year>2016</year>
</pub-date>
<volume>6</volume>
<elocation-id>20385</elocation-id>
<history>
<date date-type="received">
<day>17</day>
<month>09</month>
<year>2015</year>
</date>
<date date-type="accepted">
<day>31</day>
<month>12</month>
<year>2015</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2016, Macmillan Publishers Limited</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder>Macmillan Publishers Limited</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/">
<pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
</license-p>
</license>
</permissions>
<abstract>
<p>Seropositivity to avian influenza (AI) via low-level antibody titers has been reported in the general population and poultry-exposed individuals, raising the question whether these findings reflect true infection with AI or cross-reactivity. Here we investigated serological profiles against human and avian influenza viruses in the general population using a protein microarray platform. We hypothesized that higher antibody diversity across recent H1 and H3 influenza viruses would be associated with heterosubtypic reactivity to older pandemic- and AI viruses. We found significant heterogeneity in antibody profiles. Increased antibody diversity to seasonal influenza viruses was associated with low-level heterosubtypic antibodies to H9 and H7, but not to H5 AI virus. Individuals exposed to the recent 2009 A(H1N1) pandemic showed higher heterosubtypic reactivity. We show that there is a complex interplay between prior exposures to seasonal and recent pandemic influenza viruses and the development of heterosubtypic antibody reactivity to animal influenza viruses.</p>
</abstract>
</article-meta>
</front>
<floats-group>
<fig id="f1">
<label>Figure 1</label>
<caption>
<p>(
<bold>a</bold>
) Overall antibody reactivity against different antigens for the entire study period (week 40, 2008 to week 34, 2010) including all countries. (
<bold>b</bold>
) Development of A(H1N1)pdm09 over time for all countries combined. Pandemic onset and -course per country were previously described in de Bruin
<italic>et al.</italic>
<xref ref-type="bibr" rid="b30">30</xref>
. Both y-axes represent fluorescence values on a log10-scale.</p>
</caption>
<graphic xlink:href="srep20385-f1"></graphic>
</fig>
<fig id="f2">
<label>Figure 2</label>
<caption>
<title>Serological profiles based on adapted Shannon diversity index (ASDI) categories.</title>
<p>Recent seasonal influenza virus antigens were used to calculate ASDI per individual to summarize individual antibody profiles in one measure (blue). Assumed cross-reactive antibody responses are depicted in red (ancient- and older pandemic influenza virus strains) and green (avian influenza virus strains). Fluorescence values representing serological reactivity per antigen (x-axis) are shown on a log10-transformed y-axis.</p>
</caption>
<graphic xlink:href="srep20385-f2"></graphic>
</fig>
<fig id="f3">
<label>Figure 3</label>
<caption>
<title>Antibody profiles of samples collected after pandemic onset, stratified according to adapted Shannon diversity index (ASDI) and seropositivity status to A(H1N1)pdm09.</title>
</caption>
<graphic xlink:href="srep20385-f3"></graphic>
</fig>
<fig id="f4">
<label>Figure 4</label>
<caption>
<title>Estimated proportions of individuals with titers to avian influenza virus antigens of higher than approximately 80.</title>
<p>Proportions are presented for the total study period and split according to pre- and post pandemic periods. Reactivity to the three H5 antigens is combined.</p>
</caption>
<graphic xlink:href="srep20385-f4"></graphic>
</fig>
<table-wrap position="float" id="t1">
<label>Table 1</label>
<caption>
<title>Characteristics of study population and number of samples submitted per country and time period.</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom">
<tr>
<th rowspan="3" align="left" valign="top" charoff="50">Continent</th>
<th rowspan="3" align="center" valign="top" charoff="50">Country</th>
<th rowspan="3" align="center" valign="top" charoff="50">Country totals</th>
<th rowspan="3" align="center" valign="top" charoff="50">Row totals</th>
<th rowspan="3" align="center" valign="top" charoff="50">Pandemic onset
<sup>
<xref ref-type="fn" rid="t1-fn1">1</xref>
,
<xref ref-type="fn" rid="t1-fn1">2</xref>
</sup>
</th>
<th rowspan="3" align="center" valign="top" charoff="50">Sampling period (year/week)</th>
<th colspan="4" align="center" valign="top" charoff="50">Diversity index categories
<hr></hr>
</th>
</tr>
<tr>
<th align="center" valign="top" charoff="50">1</th>
<th align="center" valign="top" charoff="50">2</th>
<th align="center" valign="top" charoff="50">3</th>
<th align="center" valign="top" charoff="50">4</th>
</tr>
<tr>
<th align="center" valign="top" charoff="50">0–1.5</th>
<th align="center" valign="top" charoff="50">1.5–2.5</th>
<th align="center" valign="top" charoff="50">2.5–3.5</th>
<th align="center" valign="top" charoff="50">3.5–4</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td rowspan="8" align="left" valign="middle" charoff="50">North America</td>
<td rowspan="2" align="center" valign="middle" charoff="50">Canada</td>
<td rowspan="2" align="center" valign="middle" charoff="50">913</td>
<td align="center" valign="top" charoff="50">444</td>
<td align="center" valign="top" charoff="50">Pre</td>
<td align="center" valign="top" charoff="50">08/40–09/32</td>
<td align="center" valign="top" charoff="50">6.8</td>
<td align="center" valign="top" charoff="50">34.7</td>
<td align="center" valign="top" charoff="50">45</td>
<td align="center" valign="top" charoff="50">13.5</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">469</td>
<td align="center" valign="top" charoff="50">Post</td>
<td align="center" valign="top" charoff="50">09/33–10/26</td>
<td align="center" valign="top" charoff="50">1.1</td>
<td align="center" valign="top" charoff="50">17.1</td>
<td align="center" valign="top" charoff="50">48</td>
<td align="center" valign="top" charoff="50">33.9</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" charoff="50">Mexico (central)</td>
<td rowspan="2" align="center" valign="middle" charoff="50">579</td>
<td align="center" valign="top" charoff="50">272</td>
<td align="center" valign="top" charoff="50">Pre</td>
<td align="center" valign="top" charoff="50">09/26–09/45</td>
<td align="center" valign="top" charoff="50">21</td>
<td align="center" valign="top" charoff="50">40.4</td>
<td align="center" valign="top" charoff="50">32.7</td>
<td align="center" valign="top" charoff="50">6.2</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">307</td>
<td align="center" valign="top" charoff="50">Post</td>
<td align="center" valign="top" charoff="50">09/46–10/24</td>
<td align="center" valign="top" charoff="50">8.1</td>
<td align="center" valign="top" charoff="50">41.7</td>
<td align="center" valign="top" charoff="50">36.2</td>
<td align="center" valign="top" charoff="50">14</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" charoff="50">Mexico (northern)</td>
<td rowspan="2" align="center" valign="middle" charoff="50">432</td>
<td align="center" valign="top" charoff="50">432</td>
<td align="center" valign="top" charoff="50">Pre</td>
<td align="center" valign="top" charoff="50">09/01–09/044</td>
<td align="center" valign="top" charoff="50">18.8</td>
<td align="center" valign="top" charoff="50">50.9</td>
<td align="center" valign="top" charoff="50">26.6</td>
<td align="center" valign="top" charoff="50">3.7</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">0</td>
<td align="center" valign="top" charoff="50">Post</td>
<td colspan="5" align="center" valign="top" charoff="50">NA</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" charoff="50">USA</td>
<td rowspan="2" align="center" valign="middle" charoff="50">520</td>
<td align="center" valign="top" charoff="50">130</td>
<td align="center" valign="top" charoff="50">Pre</td>
<td align="center" valign="top" charoff="50">09/28–09/40</td>
<td align="center" valign="top" charoff="50">0.8</td>
<td align="center" valign="top" charoff="50">24.6</td>
<td align="center" valign="top" charoff="50">47.7</td>
<td align="center" valign="top" charoff="50">26.9</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">390</td>
<td align="center" valign="top" charoff="50">Post</td>
<td align="center" valign="top" charoff="50">09/41–10/26</td>
<td align="center" valign="top" charoff="50">0.3</td>
<td align="center" valign="top" charoff="50">8.7</td>
<td align="center" valign="top" charoff="50">38.7</td>
<td align="center" valign="top" charoff="50">52.3</td>
</tr>
<tr>
<td rowspan="10" align="left" valign="middle" charoff="50">Europe</td>
<td rowspan="2" align="center" valign="middle" charoff="50">The Netherlands</td>
<td rowspan="2" align="center" valign="middle" charoff="50">559</td>
<td align="center" valign="top" charoff="50">188</td>
<td align="center" valign="top" charoff="50">Pre</td>
<td align="center" valign="top" charoff="50">09/27–09/45</td>
<td align="center" valign="top" charoff="50">1.6</td>
<td align="center" valign="top" charoff="50">46.8</td>
<td align="center" valign="top" charoff="50">40.4</td>
<td align="center" valign="top" charoff="50">11.2</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">371</td>
<td align="center" valign="top" charoff="50">Post</td>
<td align="center" valign="top" charoff="50">09/46–10/30</td>
<td align="center" valign="top" charoff="50">0.5</td>
<td align="center" valign="top" charoff="50">32.1</td>
<td align="center" valign="top" charoff="50">50.1</td>
<td align="center" valign="top" charoff="50">17.3</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" charoff="50">Portugal</td>
<td rowspan="2" align="center" valign="middle" charoff="50">479</td>
<td align="center" valign="top" charoff="50">130</td>
<td align="center" valign="top" charoff="50">Pre</td>
<td align="center" valign="top" charoff="50">09/28–09/40</td>
<td align="center" valign="top" charoff="50">13.8</td>
<td align="center" valign="top" charoff="50">54.6</td>
<td align="center" valign="top" charoff="50">28.5</td>
<td align="center" valign="top" charoff="50">3.1</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">349</td>
<td align="center" valign="top" charoff="50">Post</td>
<td align="center" valign="top" charoff="50">09/41–10/23</td>
<td align="center" valign="top" charoff="50">5.2</td>
<td align="center" valign="top" charoff="50">33.8</td>
<td align="center" valign="top" charoff="50">44.4</td>
<td align="center" valign="top" charoff="50">16.6</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" charoff="50">Sweden</td>
<td rowspan="2" align="center" valign="middle" charoff="50">868</td>
<td align="center" valign="top" charoff="50">526</td>
<td align="center" valign="top" charoff="50">Pre</td>
<td align="center" valign="top" charoff="50">08/40–09/40</td>
<td align="center" valign="top" charoff="50">2.5</td>
<td align="center" valign="top" charoff="50">46.4</td>
<td align="center" valign="top" charoff="50">44.3</td>
<td align="center" valign="top" charoff="50">6.8</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">342</td>
<td align="center" valign="top" charoff="50">Post</td>
<td align="center" valign="top" charoff="50">09/41–10/22</td>
<td align="center" valign="top" charoff="50">0.3</td>
<td align="center" valign="top" charoff="50">20.2</td>
<td align="center" valign="top" charoff="50">49.1</td>
<td align="center" valign="top" charoff="50">30.4</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" charoff="50">Switzerland</td>
<td rowspan="2" align="center" valign="middle" charoff="50">637</td>
<td align="center" valign="top" charoff="50">180</td>
<td align="center" valign="top" charoff="50">Pre</td>
<td align="center" valign="top" charoff="50">09/23–09/40</td>
<td align="center" valign="top" charoff="50">3.3</td>
<td align="center" valign="top" charoff="50">31.1</td>
<td align="center" valign="top" charoff="50">52.2</td>
<td align="center" valign="top" charoff="50">13.3</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">457</td>
<td align="center" valign="top" charoff="50">Post</td>
<td align="center" valign="top" charoff="50">09/41–10/34</td>
<td align="center" valign="top" charoff="50">3.5</td>
<td align="center" valign="top" charoff="50">33.5</td>
<td align="center" valign="top" charoff="50">50.3</td>
<td align="center" valign="top" charoff="50">12.7</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" charoff="50">UK</td>
<td rowspan="2" align="center" valign="middle" charoff="50">568</td>
<td align="center" valign="top" charoff="50">190</td>
<td align="center" valign="top" charoff="50">Pre</td>
<td align="center" valign="top" charoff="50">09/27–09/45</td>
<td align="center" valign="top" charoff="50">7.9</td>
<td align="center" valign="top" charoff="50">39.5</td>
<td align="center" valign="top" charoff="50">40</td>
<td align="center" valign="top" charoff="50">12.6</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">378</td>
<td align="center" valign="top" charoff="50">Post</td>
<td align="center" valign="top" charoff="50">09/46–10/30</td>
<td align="center" valign="top" charoff="50">2.6</td>
<td align="center" valign="top" charoff="50">27.5</td>
<td align="center" valign="top" charoff="50">47.4</td>
<td align="center" valign="top" charoff="50">22.5</td>
</tr>
<tr>
<td rowspan="6" align="left" valign="middle" charoff="50">Asia</td>
<td rowspan="2" align="center" valign="middle" charoff="50">India</td>
<td rowspan="2" align="center" valign="middle" charoff="50">474</td>
<td align="center" valign="top" charoff="50">120</td>
<td align="center" valign="top" charoff="50">Pre</td>
<td align="center" valign="top" charoff="50">09/28–09/40</td>
<td align="center" valign="top" charoff="50">4.2</td>
<td align="center" valign="top" charoff="50">31.7</td>
<td align="center" valign="top" charoff="50">51.7</td>
<td align="center" valign="top" charoff="50">12.5</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">354</td>
<td align="center" valign="top" charoff="50">Post</td>
<td align="center" valign="top" charoff="50">09/41–10/25</td>
<td align="center" valign="top" charoff="50">3.4</td>
<td align="center" valign="top" charoff="50">34.5</td>
<td align="center" valign="top" charoff="50">48.3</td>
<td align="center" valign="top" charoff="50">13.8</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" charoff="50">Japan</td>
<td rowspan="2" align="center" valign="middle" charoff="50">530</td>
<td align="center" valign="top" charoff="50">140</td>
<td align="center" valign="top" charoff="50">Pre</td>
<td align="center" valign="top" charoff="50">09/27–09/40</td>
<td align="center" valign="top" charoff="50">1.4</td>
<td align="center" valign="top" charoff="50">21.4</td>
<td align="center" valign="top" charoff="50">51.4</td>
<td align="center" valign="top" charoff="50">25.7</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">390</td>
<td align="center" valign="top" charoff="50">Post</td>
<td align="center" valign="top" charoff="50">09/41–10/26</td>
<td align="center" valign="top" charoff="50">0.3</td>
<td align="center" valign="top" charoff="50">13.6</td>
<td align="center" valign="top" charoff="50">47.7</td>
<td align="center" valign="top" charoff="50">38.5</td>
</tr>
<tr>
<td rowspan="2" align="center" valign="middle" charoff="50">Lebanon</td>
<td rowspan="2" align="center" valign="middle" charoff="50">337</td>
<td align="center" valign="top" charoff="50">337</td>
<td align="center" valign="top" charoff="50">Pre</td>
<td align="center" valign="top" charoff="50">09/02–09/44</td>
<td align="center" valign="top" charoff="50">11.3</td>
<td align="center" valign="top" charoff="50">49.3</td>
<td align="center" valign="top" charoff="50">34.4</td>
<td align="center" valign="top" charoff="50">5</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">Post</td>
<td colspan="5" align="center" valign="top" charoff="50">NA</td>
</tr>
<tr>
<td rowspan="2" align="left" valign="middle" charoff="50">Africa</td>
<td rowspan="2" align="center" valign="middle" charoff="50">South Africa</td>
<td rowspan="2" align="center" valign="middle" charoff="50">276</td>
<td align="center" valign="top" charoff="50">248</td>
<td align="center" valign="top" charoff="50">Pre</td>
<td align="center" valign="top" charoff="50">09/29–10/15</td>
<td align="center" valign="top" charoff="50">12.1</td>
<td align="center" valign="top" charoff="50">48</td>
<td align="center" valign="top" charoff="50">35.1</td>
<td align="center" valign="top" charoff="50">4.8</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">28</td>
<td align="center" valign="top" charoff="50">Post</td>
<td align="center" valign="top" charoff="50">10/16–10/21</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">42.9</td>
<td align="center" valign="top" charoff="50">42.9</td>
<td align="center" valign="top" charoff="50">14.3</td>
</tr>
<tr>
<td rowspan="2" align="left" valign="middle" charoff="50">South America</td>
<td rowspan="2" align="center" valign="middle" charoff="50">Argentina</td>
<td rowspan="2" align="center" valign="middle" charoff="50">412</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">Pre</td>
<td colspan="5" align="center" valign="top" charoff="50">NA</td>
</tr>
<tr>
<td align="center" valign="top" charoff="50">412</td>
<td align="center" valign="top" charoff="50">Post</td>
<td align="center" valign="top" charoff="50">09/27–10/16</td>
<td align="center" valign="top" charoff="50">6.6</td>
<td align="center" valign="top" charoff="50">37.1</td>
<td align="center" valign="top" charoff="50">43.4</td>
<td align="center" valign="top" charoff="50">12.9</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Total range of study weeks:</td>
<td colspan="4" align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">08/40–10/34</td>
<td colspan="4" align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Totals per pandemic period</td>
<td align="center" valign="top" charoff="50">pre: 3337</td>
<td align="center" valign="top" charoff="50">post: 4247</td>
<td colspan="7" align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Totals per diversity category</td>
<td colspan="5" align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">416</td>
<td align="center" valign="top" charoff="50">2548</td>
<td align="center" valign="top" charoff="50">3272</td>
<td align="center" valign="top" charoff="50">1384</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">Total</td>
<td colspan="8" align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">7584</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t1-fn1">
<p>
<sup>1</sup>
Pandemic onset of A(H1N1)pdm09;
<sup>2</sup>
pre- and post pandemic onset of circulation of A(H1N1)pdm09 per respective country, percentages are represented within pandemic period; NA: not available.</p>
</fn>
<fn id="t1-fn2">
<p>Diversity index categories reflect percentage of individuals within the respective category.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="t2">
<label>Table 2</label>
<caption>
<title>Regression coefficients calculated on log2-transformed data spanning pre- and post-pandemic periods.</title>
</caption>
<table frame="hsides" rules="groups" border="1">
<colgroup>
<col align="left"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
<col align="center"></col>
</colgroup>
<thead valign="bottom">
<tr>
<th rowspan="2" align="left" valign="top" charoff="50">Outcome</th>
<th rowspan="2" align="center" valign="top" charoff="50">Intercept</th>
<th colspan="5" align="center" valign="top" charoff="50">Estimates with standard errors (SE)</th>
<th rowspan="2" align="center" valign="top" charoff="50">AdjustedR2</th>
</tr>
<tr>
<th align="center" valign="top" charoff="50">H1.99</th>
<th align="center" valign="top" charoff="50">H3.03</th>
<th align="center" valign="top" charoff="50">H1.07</th>
<th align="center" valign="top" charoff="50">H3.07</th>
<th align="center" valign="top" charoff="50">H1.09</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="left" valign="top" charoff="50">
<bold>H7.03</bold>
</td>
<td align="center" valign="top" charoff="50">5.99</td>
<td align="center" valign="top" charoff="50">-0.03</td>
<td align="center" valign="top" charoff="50">0.05</td>
<td align="center" valign="top" charoff="50">0.05</td>
<td align="center" valign="top" charoff="50">0.16</td>
<td align="center" valign="top" charoff="50">0.25</td>
<td align="center" valign="top" charoff="50">0.28</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">SE</td>
<td align="center" valign="top" charoff="50">0.14</td>
<td align="center" valign="top" charoff="50">0.013</td>
<td align="center" valign="top" charoff="50">0.011</td>
<td align="center" valign="top" charoff="50">0.013</td>
<td align="center" valign="top" charoff="50">0.012</td>
<td align="center" valign="top" charoff="50">0.009</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">*</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>H9.99</bold>
</td>
<td align="center" valign="top" charoff="50">3.90</td>
<td align="center" valign="top" charoff="50">-0.12</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">0.14</td>
<td align="center" valign="top" charoff="50">0.29</td>
<td align="center" valign="top" charoff="50">0.35</td>
<td align="center" valign="top" charoff="50">0.38</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">SE</td>
<td align="center" valign="top" charoff="50">0.15</td>
<td align="center" valign="top" charoff="50">0.014</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">0.014</td>
<td align="center" valign="top" charoff="50">0.011</td>
<td align="center" valign="top" charoff="50">0.010</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">
<bold>H9.07</bold>
</td>
<td align="center" valign="top" charoff="50">4.22</td>
<td align="center" valign="top" charoff="50">-0.05</td>
<td align="center" valign="top" charoff="50">0.08</td>
<td align="center" valign="top" charoff="50">0.11</td>
<td align="center" valign="top" charoff="50">0.16</td>
<td align="center" valign="top" charoff="50">0.32</td>
<td align="center" valign="top" charoff="50">0.37</td>
</tr>
<tr>
<td align="left" valign="top" charoff="50">SE</td>
<td align="center" valign="top" charoff="50">0.15</td>
<td align="center" valign="top" charoff="50">0.013</td>
<td align="center" valign="top" charoff="50">0.011</td>
<td align="center" valign="top" charoff="50">0.014</td>
<td align="center" valign="top" charoff="50">0.013</td>
<td align="center" valign="top" charoff="50">0.011</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
<tr>
<td align="left" valign="top" charoff="50"> </td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50">
<xref ref-type="fn" rid="t2-fn1">***</xref>
</td>
<td align="center" valign="top" charoff="50"> </td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="t2-fn1">
<p>Outcome refers to reactivity against heterologous antigens on which serological responses against recent human influenza virus antigens were regressed (explanatory variables). The number of asterisks indicates level of significance.</p>
</fn>
<fn id="t2-fn2">
<p>Significance codes: 0 ***0.001 **0.01 *0.05.1.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="t3">
<label>Table 3</label>
<graphic xlink:href="srep20385-t3"></graphic>
<table-wrap-foot>
<fn id="t3-fn1">
<p>(
<bold>A</bold>
) Number and proportions of individuals per category based on adapted Shannon diversity index (ASDI) versus pre- and post-pandemic periods. (
<bold>B</bold>
) Number and proportion of H1.09-positive and -negative individuals per diversity category before (n = 3337) and after (n = 4247) pandemic onset, respectively.</p>
</fn>
<fn id="t3-fn2">
<p>*Category of ‘Broad responders’, defined as showing the highest antibody diversity across recent seasonal human influenza viruses (H1.99, H1.07, H3.03, H3.07), expressed by the Adapted Shannon diversity indices (ASDI).</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
</record>

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