The immune correlates of protection for an avian influenza H5N1 vaccine in the ferret model using oil-in-water adjuvants
Because of the pathogenicity and low incidence of avian influenza virus infections in humans, the immune correlates of protection for avian influenza vaccines cannot be determined from clinical studies. Here, we used the ferret model to address this for an avian influenza H5N1 vaccine. Using oil-in-...
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| Veröffentlicht in: | Scientific reports 2017-03, Vol.7 (1), p.44727-44727, Article 44727 |
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| creator | Wong, Sook-San Duan, Susu DeBeauchamp, Jennifer Zanin, Mark Kercher, Lisa Sonnberg, Stephanie Fabrizio, Thomas Jeevan, Trushar Crumpton, Jeri-Carol Oshansky, Christine Sun, Yilun Tang, Li Thomas, Paul Webby, Richard |
| description | Because of the pathogenicity and low incidence of avian influenza virus infections in humans, the immune correlates of protection for avian influenza vaccines cannot be determined from clinical studies. Here, we used the ferret model to address this for an avian influenza H5N1 vaccine. Using oil-in-water adjuvants, we generated groups of ferrets with undetectable (geometric mean titer [GMT] 761.1) hemagglutination-inhibition (HAI) titers to the A/Viet Nam/1203/2004 (H5N1) virus. Ferrets were then challenged with the wild-type virus and disease severity and immunologic parameters were studied. The severity of infection and symptom profile were inversely associated with pre-challenge HAI titers in a dose-dependent manner. A vaccinated ferret with no detectable HAI-antibodies but high flu-specific IgG-antibody titers mounted rapid functional antibodies after infection and experienced milder disease compared to other ferrets in the group. Compared to naïve ferrets, all vaccinated ferrets showed improved cellular immunity in the lungs and peripheral blood. High number of IFNγ
+
CD8- T cells in the airways was associated with early viral clearance. Thus, while neutralizing antibodies are the best correlate of protection, non-neutralizing antibodies can also be protective. This should be taken into consideration in future avian influenza vaccine trials. |
| doi_str_mv | 10.1038/srep44727 |
| format | Article |
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+
CD8- T cells in the airways was associated with early viral clearance. Thus, while neutralizing antibodies are the best correlate of protection, non-neutralizing antibodies can also be protective. This should be taken into consideration in future avian influenza vaccine trials.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep44727</identifier><identifier>PMID: 28303960</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/31 ; 631/250/255/1578 ; 631/250/590/1883 ; 631/250/590/2291 ; 631/326/590/1867 ; 64 ; Adjuvants ; Antibodies ; Avian flu ; CD8 antigen ; Cell-mediated immunity ; Clinical trials ; Hemagglutination ; Humanities and Social Sciences ; Immune clearance ; Immunoglobulin G ; Immunoglobulins ; Lymphocytes T ; multidisciplinary ; Pandemics ; Pathogenicity ; Peripheral blood ; Science ; Vaccines</subject><ispartof>Scientific reports, 2017-03, Vol.7 (1), p.44727-44727, Article 44727</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group Mar 2017</rights><rights>Copyright © 2017, The Author(s) 2017 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-43954c4c4aa86ddb1b5ece30fb9bded7c4e866b0699247948152485f90b6602b3</citedby><cites>FETCH-LOGICAL-c438t-43954c4c4aa86ddb1b5ece30fb9bded7c4e866b0699247948152485f90b6602b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381113/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5381113/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28303960$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wong, Sook-San</creatorcontrib><creatorcontrib>Duan, Susu</creatorcontrib><creatorcontrib>DeBeauchamp, Jennifer</creatorcontrib><creatorcontrib>Zanin, Mark</creatorcontrib><creatorcontrib>Kercher, Lisa</creatorcontrib><creatorcontrib>Sonnberg, Stephanie</creatorcontrib><creatorcontrib>Fabrizio, Thomas</creatorcontrib><creatorcontrib>Jeevan, Trushar</creatorcontrib><creatorcontrib>Crumpton, Jeri-Carol</creatorcontrib><creatorcontrib>Oshansky, Christine</creatorcontrib><creatorcontrib>Sun, Yilun</creatorcontrib><creatorcontrib>Tang, Li</creatorcontrib><creatorcontrib>Thomas, Paul</creatorcontrib><creatorcontrib>Webby, Richard</creatorcontrib><title>The immune correlates of protection for an avian influenza H5N1 vaccine in the ferret model using oil-in-water adjuvants</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Because of the pathogenicity and low incidence of avian influenza virus infections in humans, the immune correlates of protection for avian influenza vaccines cannot be determined from clinical studies. Here, we used the ferret model to address this for an avian influenza H5N1 vaccine. Using oil-in-water adjuvants, we generated groups of ferrets with undetectable (geometric mean titer [GMT] < 10), low (GMT = 28.3), or high (GMT > 761.1) hemagglutination-inhibition (HAI) titers to the A/Viet Nam/1203/2004 (H5N1) virus. Ferrets were then challenged with the wild-type virus and disease severity and immunologic parameters were studied. The severity of infection and symptom profile were inversely associated with pre-challenge HAI titers in a dose-dependent manner. A vaccinated ferret with no detectable HAI-antibodies but high flu-specific IgG-antibody titers mounted rapid functional antibodies after infection and experienced milder disease compared to other ferrets in the group. Compared to naïve ferrets, all vaccinated ferrets showed improved cellular immunity in the lungs and peripheral blood. High number of IFNγ
+
CD8- T cells in the airways was associated with early viral clearance. Thus, while neutralizing antibodies are the best correlate of protection, non-neutralizing antibodies can also be protective. This should be taken into consideration in future avian influenza vaccine trials.</description><subject>13/31</subject><subject>631/250/255/1578</subject><subject>631/250/590/1883</subject><subject>631/250/590/2291</subject><subject>631/326/590/1867</subject><subject>64</subject><subject>Adjuvants</subject><subject>Antibodies</subject><subject>Avian flu</subject><subject>CD8 antigen</subject><subject>Cell-mediated immunity</subject><subject>Clinical trials</subject><subject>Hemagglutination</subject><subject>Humanities and Social Sciences</subject><subject>Immune clearance</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulins</subject><subject>Lymphocytes T</subject><subject>multidisciplinary</subject><subject>Pandemics</subject><subject>Pathogenicity</subject><subject>Peripheral 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Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wong, Sook-San</au><au>Duan, Susu</au><au>DeBeauchamp, Jennifer</au><au>Zanin, Mark</au><au>Kercher, Lisa</au><au>Sonnberg, Stephanie</au><au>Fabrizio, Thomas</au><au>Jeevan, Trushar</au><au>Crumpton, Jeri-Carol</au><au>Oshansky, Christine</au><au>Sun, Yilun</au><au>Tang, Li</au><au>Thomas, Paul</au><au>Webby, Richard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The immune correlates of protection for an avian influenza H5N1 vaccine in the ferret model using oil-in-water adjuvants</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-03-17</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>44727</spage><epage>44727</epage><pages>44727-44727</pages><artnum>44727</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Because of the pathogenicity and low incidence of avian influenza virus infections in humans, the immune correlates of protection for avian influenza vaccines cannot be determined from clinical studies. Here, we used the ferret model to address this for an avian influenza H5N1 vaccine. Using oil-in-water adjuvants, we generated groups of ferrets with undetectable (geometric mean titer [GMT] < 10), low (GMT = 28.3), or high (GMT > 761.1) hemagglutination-inhibition (HAI) titers to the A/Viet Nam/1203/2004 (H5N1) virus. Ferrets were then challenged with the wild-type virus and disease severity and immunologic parameters were studied. The severity of infection and symptom profile were inversely associated with pre-challenge HAI titers in a dose-dependent manner. A vaccinated ferret with no detectable HAI-antibodies but high flu-specific IgG-antibody titers mounted rapid functional antibodies after infection and experienced milder disease compared to other ferrets in the group. Compared to naïve ferrets, all vaccinated ferrets showed improved cellular immunity in the lungs and peripheral blood. High number of IFNγ
+
CD8- T cells in the airways was associated with early viral clearance. Thus, while neutralizing antibodies are the best correlate of protection, non-neutralizing antibodies can also be protective. This should be taken into consideration in future avian influenza vaccine trials.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28303960</pmid><doi>10.1038/srep44727</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/31 631/250/255/1578 631/250/590/1883 631/250/590/2291 631/326/590/1867 64 Adjuvants Antibodies Avian flu CD8 antigen Cell-mediated immunity Clinical trials Hemagglutination Humanities and Social Sciences Immune clearance Immunoglobulin G Immunoglobulins Lymphocytes T multidisciplinary Pandemics Pathogenicity Peripheral blood Science Vaccines |
| title | The immune correlates of protection for an avian influenza H5N1 vaccine in the ferret model using oil-in-water adjuvants |
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