Squalene-adjuvanted H7N9 virus vaccine induces robust humoral immune response against H7N9 and H7N7 viruses
Identifieur interne : 001013 ( Main/Exploration ); précédent : 001012; suivant : 001014Squalene-adjuvanted H7N9 virus vaccine induces robust humoral immune response against H7N9 and H7N7 viruses
Auteurs : Chia-Ying Wu [Taïwan] ; Ching-Yuan Chang [Taïwan] ; Hsiu-Hua Ma [Taïwan] ; Chiung-Wen Wang [Taïwan] ; Yung-Tsung Chen [Taïwan] ; Pei-Wen Hsiao [Taïwan] ; Ching-Chuan Chang [Taïwan] ; Chi-Hsien Chan [Taïwan] ; Chung-Cheng Liu [Taïwan] ; Juine-Ruey Chen [Taïwan]Source :
- Vaccine [ 0264-410X ] ; 2014.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Vaccin.
English descriptors
- KwdEn :
Abstract
Recent cases of avian influenza H7N9 have caused great concerns that virus may become transmittable between humans. It is imperative to develop an effective vaccine to fight against the pandemic potential of this H7N9 influenza virus to protect human from the disease. This study aims to investigate an optimized formulation for the development of H7N9 vaccines. Various doses of H7N9 inactivated whole or split-virus antigens (0.5, 1.5, or 3 μg based on hemagglutinin content) combined with squalene-based adjuvant (AddaVAX), aluminum hydroxide Al(OH)3 or without adjuvant were evaluated for the efficacy of H7N9 vaccine regiments in mice. With either H7N9 whole or split-virus based vaccines, AddaVAX-adjuvanted formulations were the most immunogenic in eliciting significant humoral immune response against H7N9 virus and exhibited strong cross-reactive response in hemagglutination inhibition (HAI) and viral-neutralization assays against H7N7 virus as well. In contrast, formulations with Al(OH)3 or without adjuvant were less immunogenic and elicited lower titers of HAI and microneutralization assays against both viruses. Dose-sparing experiments suggested that the formulation with as low as 0.004 μg of split or whole virus vaccine antigens together with 50% AddaVAX provided sufficient sero-protective HAI titers and achieved essential virus-neutralizing antibody titers against H7-subtype influenza viruses in mice. Protection experiments demonstrated that the formulation of 0.004 μg to 0.5 μg of split-virion vaccines with AddaVAX conferred full protection against viral challenge up to 100 LD50 of wild-type H7N9 virus, with 0% survival in placebo group. Taken together, our study demonstrates that squalene-based adjuvant can significantly enhance the protective efficacy of H7N9 virus vaccine and provides a useful strategy to confront the potential pandemic outbreaks of H7N9 virus.
Affiliations:
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aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Adimmune Corporation</wicri:noRegion></affiliation></author><author><name sortKey="Chang, Ching Yuan" sort="Chang, Ching Yuan" uniqKey="Chang C" first="Ching-Yuan" last="Chang">Ching-Yuan Chang</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Adimmune Corporation</s1><s2>Taichung</s2><s3>TWN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Adimmune Corporation</wicri:noRegion></affiliation></author><author><name sortKey="Ma, Hsiu Hua" sort="Ma, Hsiu Hua" uniqKey="Ma H" first="Hsiu-Hua" last="Ma">Hsiu-Hua Ma</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Genomics Research Center, Academia Sinica</s1><s2>Taipei</s2><s3>TWN</s3><sZ>3 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Taipei</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Chiung Wen" sort="Wang, Chiung Wen" uniqKey="Wang C" first="Chiung-Wen" last="Wang">Chiung-Wen Wang</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Adimmune Corporation</s1><s2>Taichung</s2><s3>TWN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Adimmune Corporation</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Yung Tsung" sort="Chen, Yung Tsung" uniqKey="Chen Y" first="Yung-Tsung" last="Chen">Yung-Tsung Chen</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Adimmune Corporation</s1><s2>Taichung</s2><s3>TWN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Adimmune Corporation</wicri:noRegion></affiliation></author><author><name sortKey="Hsiao, Pei Wen" sort="Hsiao, Pei Wen" uniqKey="Hsiao P" first="Pei-Wen" last="Hsiao">Pei-Wen Hsiao</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Agricultural Biotech Research Center, Academia Sinica</s1><s2>Taipei</s2><s3>TWN</s3><sZ>6 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Taipei</wicri:noRegion></affiliation></author><author><name sortKey="Chang, Ching Chuan" sort="Chang, Ching Chuan" uniqKey="Chang C" first="Ching-Chuan" last="Chang">Ching-Chuan Chang</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Adimmune Corporation</s1><s2>Taichung</s2><s3>TWN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Adimmune Corporation</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Chi Hsien" sort="Chan, Chi Hsien" uniqKey="Chan C" first="Chi-Hsien" last="Chan">Chi-Hsien Chan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Adimmune Corporation</s1><s2>Taichung</s2><s3>TWN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Adimmune Corporation</wicri:noRegion></affiliation></author><author><name sortKey="Liu, Chung Cheng" sort="Liu, Chung Cheng" uniqKey="Liu C" first="Chung-Cheng" last="Liu">Chung-Cheng Liu</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Adimmune Corporation</s1><s2>Taichung</s2><s3>TWN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Adimmune Corporation</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Juine Ruey" sort="Chen, Juine Ruey" uniqKey="Chen J" first="Juine-Ruey" last="Chen">Juine-Ruey Chen</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Adimmune Corporation</s1><s2>Taichung</s2><s3>TWN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Taïwan</country><wicri:noRegion>Adimmune Corporation</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Vaccine</title><title level="j" type="abbreviated">Vaccine</title><idno type="ISSN">0264-410X</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Vaccine</title><title level="j" type="abbreviated">Vaccine</title><idno type="ISSN">0264-410X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Humoral immunity</term><term>Immune response</term><term>Immunological adjuvant</term><term>Inactivated strain</term><term>Influenza</term><term>Vaccine</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Adjuvant immunologique</term><term>Vaccin</term><term>Immunité humorale</term><term>Réponse immune</term><term>Souche inactivée</term><term>Grippe</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Vaccin</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Recent cases of avian influenza H7N9 have caused great concerns that virus may become transmittable between humans. It is imperative to develop an effective vaccine to fight against the pandemic potential of this H7N9 influenza virus to protect human from the disease. This study aims to investigate an optimized formulation for the development of H7N9 vaccines. Various doses of H7N9 inactivated whole or split-virus antigens (0.5, 1.5, or 3 μg based on hemagglutinin content) combined with squalene-based adjuvant (AddaVAX), aluminum hydroxide Al(OH)<sub>3</sub> or without adjuvant were evaluated for the efficacy of H7N9 vaccine regiments in mice. With either H7N9 whole or split-virus based vaccines, AddaVAX-adjuvanted formulations were the most immunogenic in eliciting significant humoral immune response against H7N9 virus and exhibited strong cross-reactive response in hemagglutination inhibition (HAI) and viral-neutralization assays against H7N7 virus as well. In contrast, formulations with Al(OH)<sub>3</sub> or without adjuvant were less immunogenic and elicited lower titers of HAI and microneutralization assays against both viruses. Dose-sparing experiments suggested that the formulation with as low as 0.004 μg of split or whole virus vaccine antigens together with 50% AddaVAX provided sufficient sero-protective HAI titers and achieved essential virus-neutralizing antibody titers against H7-subtype influenza viruses in mice. Protection experiments demonstrated that the formulation of 0.004 μg to 0.5 μg of split-virion vaccines with AddaVAX conferred full protection against viral challenge up to 100 LD50 of wild-type H7N9 virus, with 0% survival in placebo group. Taken together, our study demonstrates that squalene-based adjuvant can significantly enhance the protective efficacy of H7N9 virus vaccine and provides a useful strategy to confront the potential pandemic outbreaks of H7N9 virus.</div></front></TEI><affiliations><list><country><li>Taïwan</li></country></list><tree><country name="Taïwan"><noRegion><name sortKey="Wu, Chia Ying" sort="Wu, Chia Ying" uniqKey="Wu C" first="Chia-Ying" last="Wu">Chia-Ying Wu</name></noRegion><name sortKey="Chan, Chi Hsien" sort="Chan, Chi Hsien" uniqKey="Chan C" first="Chi-Hsien" last="Chan">Chi-Hsien Chan</name><name sortKey="Chang, Ching Chuan" sort="Chang, Ching Chuan" uniqKey="Chang C" first="Ching-Chuan" last="Chang">Ching-Chuan Chang</name><name sortKey="Chang, Ching Yuan" sort="Chang, Ching Yuan" uniqKey="Chang C" first="Ching-Yuan" last="Chang">Ching-Yuan Chang</name><name sortKey="Chen, Juine Ruey" sort="Chen, Juine Ruey" uniqKey="Chen J" first="Juine-Ruey" last="Chen">Juine-Ruey Chen</name><name sortKey="Chen, Yung Tsung" sort="Chen, Yung Tsung" uniqKey="Chen Y" first="Yung-Tsung" last="Chen">Yung-Tsung Chen</name><name sortKey="Hsiao, Pei Wen" sort="Hsiao, Pei Wen" uniqKey="Hsiao P" first="Pei-Wen" last="Hsiao">Pei-Wen Hsiao</name><name sortKey="Liu, Chung Cheng" sort="Liu, Chung Cheng" uniqKey="Liu C" first="Chung-Cheng" last="Liu">Chung-Cheng Liu</name><name sortKey="Ma, Hsiu Hua" sort="Ma, Hsiu Hua" uniqKey="Ma H" first="Hsiu-Hua" last="Ma">Hsiu-Hua Ma</name><name sortKey="Wang, Chiung Wen" sort="Wang, Chiung Wen" uniqKey="Wang C" first="Chiung-Wen" last="Wang">Chiung-Wen Wang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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