A plant-derived VLP influenza vaccine elicits a balanced immune response even in very old mice with co-morbidities
The elderly are at high risk from influenza, in part because immunity wanes with age and through the accumulation of comorbidities. A novel plant-derived virus-like-particle (VLP) vaccine bearing influenza hemagglutinin can induce a balanced humoral and cellular response in old mice (16-18 months) w...
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| Veröffentlicht in: | PloS one 2019-01, Vol.14 (1), p.e0210009-e0210009 |
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| creator | Hodgins, Breanna Pillet, Stephane Landry, Nathalie Ward, Brian James |
| description | The elderly are at high risk from influenza, in part because immunity wanes with age and through the accumulation of comorbidities. A novel plant-derived virus-like-particle (VLP) vaccine bearing influenza hemagglutinin can induce a balanced humoral and cellular response in old mice (16-18 months) while split virion vaccines elicit mostly antibodies. Because mice also collect comorbidities and lose immune competence as they age, we wished to determine how the plant-derived VLP vaccine would perform in animals approaching the end of their life-span.
Old (24-26 months) female BALB/c mice received two intramuscular doses of H1-VLP vaccine, an inactivated H1N1 vaccine (IIV) (both based on A/H1N1/California/07/09) (3μg each) or PBS. Serum was collected on day 42 and humoral responses were measured by enzyme-linked immunosorbent assay (ELISA), microneutralization (MN) and hemagglutination inhibition (HI) assays. Influenza-specific splenocyte CD4+ & CD8+ T cell responses were measured by flow cytometry. Full body computed tomography (CT) and structured necropsies were performed on day 42. Comorbidities including reduced lung volume (kyphosis), masses, abscesses, etc. were assessed using a standard scoring system (1-21) and mice with scores ≥5 were considered to have important comorbidities.
Overall, 53.3% of the animals had significant comorbidities. Three weeks post-boost, HI and MN titres were mostly undetectable but ELISA titres were significantly higher in the H1-VLP animals compared to the IIV group (GMT (95% CI): 961 (427, 2163) vs 425 (200, 903): p = 0.03). Both CD4+(TNFα, IFNγ) and CD8+ (IFNγ) T cell responses were also greater in the H1-VLP group than the IIV.
Even in very old mice with comorbidities, the plant-made H1-VLP vaccine elicited a stronger and more balanced immune response than IIV. Animals with fewer comorbidities tended to have the better composite (humoral and cellular) responses. These novel vaccines have the potential to address some of the limitations of current vaccines in the elderly. |
| doi_str_mv | 10.1371/journal.pone.0210009 |
| format | Article |
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Old (24-26 months) female BALB/c mice received two intramuscular doses of H1-VLP vaccine, an inactivated H1N1 vaccine (IIV) (both based on A/H1N1/California/07/09) (3μg each) or PBS. Serum was collected on day 42 and humoral responses were measured by enzyme-linked immunosorbent assay (ELISA), microneutralization (MN) and hemagglutination inhibition (HI) assays. Influenza-specific splenocyte CD4+ & CD8+ T cell responses were measured by flow cytometry. Full body computed tomography (CT) and structured necropsies were performed on day 42. Comorbidities including reduced lung volume (kyphosis), masses, abscesses, etc. were assessed using a standard scoring system (1-21) and mice with scores ≥5 were considered to have important comorbidities.
Overall, 53.3% of the animals had significant comorbidities. Three weeks post-boost, HI and MN titres were mostly undetectable but ELISA titres were significantly higher in the H1-VLP animals compared to the IIV group (GMT (95% CI): 961 (427, 2163) vs 425 (200, 903): p = 0.03). Both CD4+(TNFα, IFNγ) and CD8+ (IFNγ) T cell responses were also greater in the H1-VLP group than the IIV.
Even in very old mice with comorbidities, the plant-made H1-VLP vaccine elicited a stronger and more balanced immune response than IIV. Animals with fewer comorbidities tended to have the better composite (humoral and cellular) responses. These novel vaccines have the potential to address some of the limitations of current vaccines in the elderly.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0210009</identifier><identifier>PMID: 30629622</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Abscesses ; Age ; Aging ; Aging - immunology ; Analysis ; Animals ; Antibodies ; Antibodies, Viral - blood ; Antibodies, Viral - immunology ; Antigens ; Biology and Life Sciences ; CD4 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes - immunology ; Comorbidity ; Computed tomography ; Drug dosages ; Enzyme-linked immunosorbent assay ; Flow cytometry ; Geriatrics ; Gerontology ; Health aspects ; Hemagglutination inhibition ; Hemagglutinin Glycoproteins, Influenza Virus - immunology ; Hemagglutinins ; Humans ; Immune response ; Immune system ; Immunity ; Influenza ; Influenza A Virus, H1N1 Subtype - immunology ; Influenza A Virus, H1N1 Subtype - physiology ; Influenza Vaccines - immunology ; Kyphosis ; Laboratories ; Lungs ; Lymphocytes ; Lymphocytes T ; Medicine and Health Sciences ; Mice ; Mice, Inbred BALB C ; Nicotiana - genetics ; Older people ; Orthomyxoviridae Infections - blood ; Orthomyxoviridae Infections - immunology ; Orthomyxoviridae Infections - virology ; People and Places ; Plant viruses ; Plants ; Recombinant Proteins - immunology ; Research and Analysis Methods ; Systematic review ; T cells ; Tumor necrosis factor-α ; Vaccination - methods ; Vaccines ; Vaccines, Inactivated - immunology ; Vaccines, Virus-Like Particle - genetics ; Vaccines, Virus-Like Particle - immunology ; Virions ; Viruses ; γ-Interferon</subject><ispartof>PloS one, 2019-01, Vol.14 (1), p.e0210009-e0210009</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Hodgins et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 Hodgins et al 2019 Hodgins et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-c2108e150399a37d0dc693df9eef9dfd17205233e8e82602e6a43a5a64978fb43</citedby><cites>FETCH-LOGICAL-c692t-c2108e150399a37d0dc693df9eef9dfd17205233e8e82602e6a43a5a64978fb43</cites><orcidid>0000-0003-3251-958X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328122/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328122/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30629622$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Krammer, Florian</contributor><creatorcontrib>Hodgins, Breanna</creatorcontrib><creatorcontrib>Pillet, Stephane</creatorcontrib><creatorcontrib>Landry, Nathalie</creatorcontrib><creatorcontrib>Ward, Brian James</creatorcontrib><title>A plant-derived VLP influenza vaccine elicits a balanced immune response even in very old mice with co-morbidities</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The elderly are at high risk from influenza, in part because immunity wanes with age and through the accumulation of comorbidities. A novel plant-derived virus-like-particle (VLP) vaccine bearing influenza hemagglutinin can induce a balanced humoral and cellular response in old mice (16-18 months) while split virion vaccines elicit mostly antibodies. Because mice also collect comorbidities and lose immune competence as they age, we wished to determine how the plant-derived VLP vaccine would perform in animals approaching the end of their life-span.
Old (24-26 months) female BALB/c mice received two intramuscular doses of H1-VLP vaccine, an inactivated H1N1 vaccine (IIV) (both based on A/H1N1/California/07/09) (3μg each) or PBS. Serum was collected on day 42 and humoral responses were measured by enzyme-linked immunosorbent assay (ELISA), microneutralization (MN) and hemagglutination inhibition (HI) assays. Influenza-specific splenocyte CD4+ & CD8+ T cell responses were measured by flow cytometry. Full body computed tomography (CT) and structured necropsies were performed on day 42. Comorbidities including reduced lung volume (kyphosis), masses, abscesses, etc. were assessed using a standard scoring system (1-21) and mice with scores ≥5 were considered to have important comorbidities.
Overall, 53.3% of the animals had significant comorbidities. Three weeks post-boost, HI and MN titres were mostly undetectable but ELISA titres were significantly higher in the H1-VLP animals compared to the IIV group (GMT (95% CI): 961 (427, 2163) vs 425 (200, 903): p = 0.03). Both CD4+(TNFα, IFNγ) and CD8+ (IFNγ) T cell responses were also greater in the H1-VLP group than the IIV.
Even in very old mice with comorbidities, the plant-made H1-VLP vaccine elicited a stronger and more balanced immune response than IIV. Animals with fewer comorbidities tended to have the better composite (humoral and cellular) responses. These novel vaccines have the potential to address some of the limitations of current vaccines in the elderly.</description><subject>Abscesses</subject><subject>Age</subject><subject>Aging</subject><subject>Aging - immunology</subject><subject>Analysis</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibodies, Viral - blood</subject><subject>Antibodies, Viral - immunology</subject><subject>Antigens</subject><subject>Biology and Life Sciences</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Comorbidity</subject><subject>Computed tomography</subject><subject>Drug dosages</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Flow cytometry</subject><subject>Geriatrics</subject><subject>Gerontology</subject><subject>Health aspects</subject><subject>Hemagglutination inhibition</subject><subject>Hemagglutinin Glycoproteins, Influenza Virus - immunology</subject><subject>Hemagglutinins</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunity</subject><subject>Influenza</subject><subject>Influenza A Virus, H1N1 Subtype - immunology</subject><subject>Influenza A Virus, H1N1 Subtype - physiology</subject><subject>Influenza Vaccines - immunology</subject><subject>Kyphosis</subject><subject>Laboratories</subject><subject>Lungs</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Medicine and Health Sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nicotiana - genetics</subject><subject>Older people</subject><subject>Orthomyxoviridae Infections - blood</subject><subject>Orthomyxoviridae Infections - immunology</subject><subject>Orthomyxoviridae Infections - virology</subject><subject>People and Places</subject><subject>Plant viruses</subject><subject>Plants</subject><subject>Recombinant Proteins - immunology</subject><subject>Research and Analysis Methods</subject><subject>Systematic review</subject><subject>T cells</subject><subject>Tumor necrosis factor-α</subject><subject>Vaccination - methods</subject><subject>Vaccines</subject><subject>Vaccines, Inactivated - immunology</subject><subject>Vaccines, Virus-Like Particle - genetics</subject><subject>Vaccines, Virus-Like Particle - immunology</subject><subject>Virions</subject><subject>Viruses</subject><subject>γ-Interferon</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1tv0zAUxyMEYmPwDRBEQkLwkOJL4yQvSNXEpVKlIS57tRz7pPXkxJ2dFMan55RmU4P2gPxg6_h3_va5JclzSmaUF_TdlR9Cp9xs6zuYEUYJIdWD5JRWnGWCEf7w6HySPInxipCcl0I8Tk44EawSjJ0mYZFuner6zECwOzDp5epLarvGDdD9VulOaW07SMFZbfuYqrRWiGsEbdsOeBMg4g8iIjvo0DPdQbhJvTNpazWkP22_SbXPWh9qa2xvIT5NHjXKRXg27mfJj48fvp9_zlYXn5bni1WmRcX6TGNIJdCc8KpSvDDEoJ2bpgJoKtMYWjCSM86hhJIJwkCoOVe5EvOqKJt6zs-SlwfdrfNRjumKklEhKBU5FUgsD4Tx6kpug21VuJFeWfnX4MNaqtBb7UCyoja1UMbUAHOiRAm4N7SgDSnnIHLUej--NtQtGA1dH5SbiE5vOruRa7-TgrOSMoYCb0aB4K8HiL1sbdTgMN3gh_2_CywnQRLRV_-g90c3UmuFAWBNPb6r96JykYsKW6Dke2p2D4XLABYQe6uxaJ84vJ04INPDr36thhjl8tvX_2cvLqfs6yN2A8r1m-jd0Ftsryk4P4A6-BgDNHdJpkTuR-M2G3I_GnIcDXR7cVygO6fbWeB_APzjCWQ</recordid><startdate>20190110</startdate><enddate>20190110</enddate><creator>Hodgins, Breanna</creator><creator>Pillet, Stephane</creator><creator>Landry, Nathalie</creator><creator>Ward, Brian James</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-3251-958X</orcidid></search><sort><creationdate>20190110</creationdate><title>A plant-derived VLP influenza vaccine elicits a balanced immune response even in very old mice with co-morbidities</title><author>Hodgins, Breanna ; Pillet, Stephane ; Landry, Nathalie ; Ward, Brian James</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-c2108e150399a37d0dc693df9eef9dfd17205233e8e82602e6a43a5a64978fb43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Abscesses</topic><topic>Age</topic><topic>Aging</topic><topic>Aging - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hodgins, Breanna</au><au>Pillet, Stephane</au><au>Landry, Nathalie</au><au>Ward, Brian James</au><au>Krammer, Florian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A plant-derived VLP influenza vaccine elicits a balanced immune response even in very old mice with co-morbidities</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-01-10</date><risdate>2019</risdate><volume>14</volume><issue>1</issue><spage>e0210009</spage><epage>e0210009</epage><pages>e0210009-e0210009</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The elderly are at high risk from influenza, in part because immunity wanes with age and through the accumulation of comorbidities. A novel plant-derived virus-like-particle (VLP) vaccine bearing influenza hemagglutinin can induce a balanced humoral and cellular response in old mice (16-18 months) while split virion vaccines elicit mostly antibodies. Because mice also collect comorbidities and lose immune competence as they age, we wished to determine how the plant-derived VLP vaccine would perform in animals approaching the end of their life-span.
Old (24-26 months) female BALB/c mice received two intramuscular doses of H1-VLP vaccine, an inactivated H1N1 vaccine (IIV) (both based on A/H1N1/California/07/09) (3μg each) or PBS. Serum was collected on day 42 and humoral responses were measured by enzyme-linked immunosorbent assay (ELISA), microneutralization (MN) and hemagglutination inhibition (HI) assays. Influenza-specific splenocyte CD4+ & CD8+ T cell responses were measured by flow cytometry. Full body computed tomography (CT) and structured necropsies were performed on day 42. Comorbidities including reduced lung volume (kyphosis), masses, abscesses, etc. were assessed using a standard scoring system (1-21) and mice with scores ≥5 were considered to have important comorbidities.
Overall, 53.3% of the animals had significant comorbidities. Three weeks post-boost, HI and MN titres were mostly undetectable but ELISA titres were significantly higher in the H1-VLP animals compared to the IIV group (GMT (95% CI): 961 (427, 2163) vs 425 (200, 903): p = 0.03). Both CD4+(TNFα, IFNγ) and CD8+ (IFNγ) T cell responses were also greater in the H1-VLP group than the IIV.
Even in very old mice with comorbidities, the plant-made H1-VLP vaccine elicited a stronger and more balanced immune response than IIV. Animals with fewer comorbidities tended to have the better composite (humoral and cellular) responses. These novel vaccines have the potential to address some of the limitations of current vaccines in the elderly.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>30629622</pmid><doi>10.1371/journal.pone.0210009</doi><orcidid>https://orcid.org/0000-0003-3251-958X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2019-01, Vol.14 (1), p.e0210009-e0210009 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2166116516 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Abscesses Age Aging Aging - immunology Analysis Animals Antibodies Antibodies, Viral - blood Antibodies, Viral - immunology Antigens Biology and Life Sciences CD4 antigen CD8 antigen CD8-Positive T-Lymphocytes - immunology Comorbidity Computed tomography Drug dosages Enzyme-linked immunosorbent assay Flow cytometry Geriatrics Gerontology Health aspects Hemagglutination inhibition Hemagglutinin Glycoproteins, Influenza Virus - immunology Hemagglutinins Humans Immune response Immune system Immunity Influenza Influenza A Virus, H1N1 Subtype - immunology Influenza A Virus, H1N1 Subtype - physiology Influenza Vaccines - immunology Kyphosis Laboratories Lungs Lymphocytes Lymphocytes T Medicine and Health Sciences Mice Mice, Inbred BALB C Nicotiana - genetics Older people Orthomyxoviridae Infections - blood Orthomyxoviridae Infections - immunology Orthomyxoviridae Infections - virology People and Places Plant viruses Plants Recombinant Proteins - immunology Research and Analysis Methods Systematic review T cells Tumor necrosis factor-α Vaccination - methods Vaccines Vaccines, Inactivated - immunology Vaccines, Virus-Like Particle - genetics Vaccines, Virus-Like Particle - immunology Virions Viruses γ-Interferon |
| title | A plant-derived VLP influenza vaccine elicits a balanced immune response even in very old mice with co-morbidities |
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