Impact of flavivirus vaccine-induced immunity on primary Zika virus antibody response in humans
Zika virus has recently spread to South- and Central America, causing congenital birth defects and neurological complications. Many people at risk are flavivirus pre-immune due to prior infections with other flaviviruses (e.g. dengue virus) or flavivirus vaccinations. Since pre-existing cross-reacti...
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| Veröffentlicht in: | PLoS neglected tropical diseases 2020-02, Vol.14 (2), p.e0008034-e0008034 |
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| creator | Malafa, Stefan Medits, Iris Aberle, Judith H Aberle, Stephan W Haslwanter, Denise Tsouchnikas, Georgios Wölfel, Silke Huber, Kristina L Percivalle, Elena Cherpillod, Pascal Thaler, Melissa Roßbacher, Lena Kundi, Michael Heinz, Franz X Stiasny, Karin |
| description | Zika virus has recently spread to South- and Central America, causing congenital birth defects and neurological complications. Many people at risk are flavivirus pre-immune due to prior infections with other flaviviruses (e.g. dengue virus) or flavivirus vaccinations. Since pre-existing cross-reactive immunity can potentially modulate antibody responses to Zika virus infection and may affect the outcome of disease, we analyzed fine-specificity as well as virus-neutralizing and infection-enhancing activities of antibodies induced by a primary Zika virus infection in flavivirus-naïve as well as yellow fever- and/or tick-borne encephalitis-vaccinated individuals.
Antibodies in sera from convalescent Zika patients with and without vaccine-induced immunity were assessed by ELISA with respect to Zika virus-specificity and flavivirus cross-reactivity. Functional analyses included virus neutralization and infection-enhancement. The contribution of IgM and cross-reactive antibodies to these properties was determined by depletion experiments.
Pre-existing flavivirus immunity had a strong influence on the antibody response in primary Zika virus infections, resulting in higher titers of broadly flavivirus cross-reactive antibodies and slightly lower levels of Zika virus-specific IgM. Antibody-dependent enhancement (ADE) of Zika virus was mediated by sub-neutralizing concentrations of specific IgG but not by cross-reactive antibodies. This effect was potently counteracted by the presence of neutralizing IgM. Broadly cross-reactive antibodies were able to both neutralize and enhance infection of dengue virus but not Zika virus, indicating a different exposure of conserved sequence elements in the two viruses.
Our data point to an important role of flavivirus-specific IgM during the transient early stages of infection, by contributing substantially to neutralization and by counteracting ADE. In addition, our results highlight structural differences between strains of Zika and dengue viruses that are used for analyzing infection-enhancement by cross-reactive antibodies. These findings underscore the possible impact of specific antibody patterns on flavivirus disease and vaccination efficacy. |
| doi_str_mv | 10.1371/journal.pntd.0008034 |
| format | Article |
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Antibodies in sera from convalescent Zika patients with and without vaccine-induced immunity were assessed by ELISA with respect to Zika virus-specificity and flavivirus cross-reactivity. Functional analyses included virus neutralization and infection-enhancement. The contribution of IgM and cross-reactive antibodies to these properties was determined by depletion experiments.
Pre-existing flavivirus immunity had a strong influence on the antibody response in primary Zika virus infections, resulting in higher titers of broadly flavivirus cross-reactive antibodies and slightly lower levels of Zika virus-specific IgM. Antibody-dependent enhancement (ADE) of Zika virus was mediated by sub-neutralizing concentrations of specific IgG but not by cross-reactive antibodies. This effect was potently counteracted by the presence of neutralizing IgM. Broadly cross-reactive antibodies were able to both neutralize and enhance infection of dengue virus but not Zika virus, indicating a different exposure of conserved sequence elements in the two viruses.
Our data point to an important role of flavivirus-specific IgM during the transient early stages of infection, by contributing substantially to neutralization and by counteracting ADE. In addition, our results highlight structural differences between strains of Zika and dengue viruses that are used for analyzing infection-enhancement by cross-reactive antibodies. These findings underscore the possible impact of specific antibody patterns on flavivirus disease and vaccination efficacy.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0008034</identifier><identifier>PMID: 32017766</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Antibodies ; Antibodies, Viral - blood ; Antibody Affinity ; Antibody response ; Antigens, Viral - immunology ; Biology and life sciences ; Birth defects ; Complications ; Complications and side effects ; Congenital defects ; Conserved sequence ; Cross-reactivity ; Data points ; Defects ; Dengue ; Dengue fever ; Dengue virus ; Depletion ; Disease control ; Diseases ; ELISA ; Encephalitis ; Enzyme-Linked Immunosorbent Assay ; Epidemics ; Epidemiology ; Genetic disorders ; Guillain-Barre syndrome ; Human diseases ; Humans ; Immunity ; Immunoglobulin G ; Immunoglobulin G - blood ; Immunoglobulin M ; Immunoglobulins ; Infection ; Infections ; Laboratories ; Medical research ; Medicine ; Medicine and Health Sciences ; Microbiological strains ; Neurological complications ; Neutralization ; Neutralization Tests ; Neutralizing ; Polyethylene Glycols ; Research and Analysis Methods ; Scientific equipment industry ; Specificity ; Strains ; Tick-borne diseases ; Tick-borne encephalitis ; Tropical diseases ; Vaccination ; Vaccines ; Vector-borne diseases ; Viral Envelope Proteins - immunology ; Viral Vaccines - immunology ; Virology ; Virus diseases ; Viruses ; West Nile virus ; Yellow fever ; Zika virus ; Zika Virus - genetics ; Zika Virus - immunology ; Zika Virus Infection - prevention & control</subject><ispartof>PLoS neglected tropical diseases, 2020-02, Vol.14 (2), p.e0008034-e0008034</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Malafa 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>2020 Malafa et al 2020 Malafa et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c624t-633f71ed0f286da7cc87f2acd79e3c9d72463875831e9cc984cb8f5e5ec8b7f13</citedby><cites>FETCH-LOGICAL-c624t-633f71ed0f286da7cc87f2acd79e3c9d72463875831e9cc984cb8f5e5ec8b7f13</cites><orcidid>0000-0002-1902-8674 ; 0000-0002-7191-4331 ; 0000-0002-0222-9832 ; 0000-0002-2707-3213 ; 0000-0003-2727-0468 ; 0000-0003-3595-3074</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/PMC7021315/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7021315/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32017766$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Gubler, Duane J.</contributor><creatorcontrib>Malafa, Stefan</creatorcontrib><creatorcontrib>Medits, Iris</creatorcontrib><creatorcontrib>Aberle, Judith H</creatorcontrib><creatorcontrib>Aberle, Stephan W</creatorcontrib><creatorcontrib>Haslwanter, Denise</creatorcontrib><creatorcontrib>Tsouchnikas, Georgios</creatorcontrib><creatorcontrib>Wölfel, Silke</creatorcontrib><creatorcontrib>Huber, Kristina L</creatorcontrib><creatorcontrib>Percivalle, Elena</creatorcontrib><creatorcontrib>Cherpillod, Pascal</creatorcontrib><creatorcontrib>Thaler, Melissa</creatorcontrib><creatorcontrib>Roßbacher, Lena</creatorcontrib><creatorcontrib>Kundi, Michael</creatorcontrib><creatorcontrib>Heinz, Franz X</creatorcontrib><creatorcontrib>Stiasny, Karin</creatorcontrib><title>Impact of flavivirus vaccine-induced immunity on primary Zika virus antibody response in humans</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Zika virus has recently spread to South- and Central America, causing congenital birth defects and neurological complications. Many people at risk are flavivirus pre-immune due to prior infections with other flaviviruses (e.g. dengue virus) or flavivirus vaccinations. Since pre-existing cross-reactive immunity can potentially modulate antibody responses to Zika virus infection and may affect the outcome of disease, we analyzed fine-specificity as well as virus-neutralizing and infection-enhancing activities of antibodies induced by a primary Zika virus infection in flavivirus-naïve as well as yellow fever- and/or tick-borne encephalitis-vaccinated individuals.
Antibodies in sera from convalescent Zika patients with and without vaccine-induced immunity were assessed by ELISA with respect to Zika virus-specificity and flavivirus cross-reactivity. Functional analyses included virus neutralization and infection-enhancement. The contribution of IgM and cross-reactive antibodies to these properties was determined by depletion experiments.
Pre-existing flavivirus immunity had a strong influence on the antibody response in primary Zika virus infections, resulting in higher titers of broadly flavivirus cross-reactive antibodies and slightly lower levels of Zika virus-specific IgM. Antibody-dependent enhancement (ADE) of Zika virus was mediated by sub-neutralizing concentrations of specific IgG but not by cross-reactive antibodies. This effect was potently counteracted by the presence of neutralizing IgM. Broadly cross-reactive antibodies were able to both neutralize and enhance infection of dengue virus but not Zika virus, indicating a different exposure of conserved sequence elements in the two viruses.
Our data point to an important role of flavivirus-specific IgM during the transient early stages of infection, by contributing substantially to neutralization and by counteracting ADE. In addition, our results highlight structural differences between strains of Zika and dengue viruses that are used for analyzing infection-enhancement by cross-reactive antibodies. These findings underscore the possible impact of specific antibody patterns on flavivirus disease and vaccination efficacy.</description><subject>Analysis</subject><subject>Antibodies</subject><subject>Antibodies, Viral - blood</subject><subject>Antibody Affinity</subject><subject>Antibody response</subject><subject>Antigens, Viral - immunology</subject><subject>Biology and life sciences</subject><subject>Birth defects</subject><subject>Complications</subject><subject>Complications and side effects</subject><subject>Congenital defects</subject><subject>Conserved sequence</subject><subject>Cross-reactivity</subject><subject>Data points</subject><subject>Defects</subject><subject>Dengue</subject><subject>Dengue fever</subject><subject>Dengue virus</subject><subject>Depletion</subject><subject>Disease control</subject><subject>Diseases</subject><subject>ELISA</subject><subject>Encephalitis</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epidemics</subject><subject>Epidemiology</subject><subject>Genetic disorders</subject><subject>Guillain-Barre syndrome</subject><subject>Human diseases</subject><subject>Humans</subject><subject>Immunity</subject><subject>Immunoglobulin G</subject><subject>Immunoglobulin G - blood</subject><subject>Immunoglobulin M</subject><subject>Immunoglobulins</subject><subject>Infection</subject><subject>Infections</subject><subject>Laboratories</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Microbiological strains</subject><subject>Neurological complications</subject><subject>Neutralization</subject><subject>Neutralization Tests</subject><subject>Neutralizing</subject><subject>Polyethylene Glycols</subject><subject>Research and Analysis Methods</subject><subject>Scientific equipment industry</subject><subject>Specificity</subject><subject>Strains</subject><subject>Tick-borne diseases</subject><subject>Tick-borne encephalitis</subject><subject>Tropical diseases</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Vector-borne diseases</subject><subject>Viral Envelope Proteins - immunology</subject><subject>Viral Vaccines - immunology</subject><subject>Virology</subject><subject>Virus diseases</subject><subject>Viruses</subject><subject>West Nile virus</subject><subject>Yellow fever</subject><subject>Zika virus</subject><subject>Zika Virus - genetics</subject><subject>Zika Virus - immunology</subject><subject>Zika Virus Infection - prevention & control</subject><issn>1935-2735</issn><issn>1935-2727</issn><issn>1935-2735</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</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>DOA</sourceid><recordid>eNptkl2LEzEUhgdR3LX6D0QDgnjTmkySSeZGWBY_Cgve6I03IZOctKkzSU1mCv33ztjZpZUlFwnJc97zkbcoXhO8IlSQj7s4pKDb1T70doUxlpiyJ8U1qSlfloLyp2fnq-JFzjuMec0leV5c0RITIarqulDrbq9Nj6JDrtUHf_BpyOigjfEBlj7YwYBFvuuG4PsjigHtk-90OqJf_rdGJ1yH3jfRHlGCvI8hA_IBbYdOh_yyeOZ0m-HVvC-Kn18-_7j9trz7_nV9e3O3NFXJ-mVFqRMELHalrKwWxkjhSm2sqIGa2oqSVVQKLimB2phaMtNIx4GDkY1whC6KtyfdfRuzmmeTVUmFEJjVgo_E-kTYqHdq7kJF7dW_i5g2SqfemxZU0zheawKiYZgJh6Uh1oGgIGvJsYFR69OcbWg6sAZCn3R7IXr5EvxWbeJBCVwSSqZiPswCKf4ZIPeq89lA2-oAcZjq5oRJymQ5ou_-Qx_vbqY2emzABxfHvGYSVTcVqXjJ6tEIi2L1CDUuC503MYDz4_1FwPuzgC3ott_m2A69H7_5EmQn0KSYcwL3MAyC1eTX-6rV5Fc1-3UMe3M-yIege4PSvxnB6MI</recordid><startdate>20200201</startdate><enddate>20200201</enddate><creator>Malafa, Stefan</creator><creator>Medits, Iris</creator><creator>Aberle, Judith H</creator><creator>Aberle, Stephan W</creator><creator>Haslwanter, Denise</creator><creator>Tsouchnikas, Georgios</creator><creator>Wölfel, Silke</creator><creator>Huber, Kristina L</creator><creator>Percivalle, Elena</creator><creator>Cherpillod, Pascal</creator><creator>Thaler, Melissa</creator><creator>Roßbacher, Lena</creator><creator>Kundi, Michael</creator><creator>Heinz, Franz X</creator><creator>Stiasny, Karin</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>3V.</scope><scope>7QL</scope><scope>7SS</scope><scope>7T2</scope><scope>7T7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-1902-8674</orcidid><orcidid>https://orcid.org/0000-0002-7191-4331</orcidid><orcidid>https://orcid.org/0000-0002-0222-9832</orcidid><orcidid>https://orcid.org/0000-0002-2707-3213</orcidid><orcidid>https://orcid.org/0000-0003-2727-0468</orcidid><orcidid>https://orcid.org/0000-0003-3595-3074</orcidid></search><sort><creationdate>20200201</creationdate><title>Impact of flavivirus vaccine-induced immunity on primary Zika virus antibody response in humans</title><author>Malafa, Stefan ; Medits, Iris ; Aberle, Judith H ; Aberle, Stephan W ; Haslwanter, Denise ; Tsouchnikas, Georgios ; Wölfel, Silke ; Huber, Kristina L ; Percivalle, Elena ; Cherpillod, Pascal ; Thaler, Melissa ; Roßbacher, Lena ; Kundi, Michael ; Heinz, Franz X ; Stiasny, Karin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c624t-633f71ed0f286da7cc87f2acd79e3c9d72463875831e9cc984cb8f5e5ec8b7f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Analysis</topic><topic>Antibodies</topic><topic>Antibodies, Viral - blood</topic><topic>Antibody Affinity</topic><topic>Antibody response</topic><topic>Antigens, Viral - immunology</topic><topic>Biology and life sciences</topic><topic>Birth defects</topic><topic>Complications</topic><topic>Complications and side effects</topic><topic>Congenital defects</topic><topic>Conserved sequence</topic><topic>Cross-reactivity</topic><topic>Data points</topic><topic>Defects</topic><topic>Dengue</topic><topic>Dengue fever</topic><topic>Dengue virus</topic><topic>Depletion</topic><topic>Disease control</topic><topic>Diseases</topic><topic>ELISA</topic><topic>Encephalitis</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Epidemics</topic><topic>Epidemiology</topic><topic>Genetic disorders</topic><topic>Guillain-Barre syndrome</topic><topic>Human diseases</topic><topic>Humans</topic><topic>Immunity</topic><topic>Immunoglobulin G</topic><topic>Immunoglobulin G - blood</topic><topic>Immunoglobulin M</topic><topic>Immunoglobulins</topic><topic>Infection</topic><topic>Infections</topic><topic>Laboratories</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Microbiological strains</topic><topic>Neurological complications</topic><topic>Neutralization</topic><topic>Neutralization Tests</topic><topic>Neutralizing</topic><topic>Polyethylene Glycols</topic><topic>Research and Analysis Methods</topic><topic>Scientific equipment industry</topic><topic>Specificity</topic><topic>Strains</topic><topic>Tick-borne diseases</topic><topic>Tick-borne encephalitis</topic><topic>Tropical diseases</topic><topic>Vaccination</topic><topic>Vaccines</topic><topic>Vector-borne diseases</topic><topic>Viral Envelope Proteins - immunology</topic><topic>Viral Vaccines - immunology</topic><topic>Virology</topic><topic>Virus diseases</topic><topic>Viruses</topic><topic>West Nile virus</topic><topic>Yellow fever</topic><topic>Zika virus</topic><topic>Zika Virus - genetics</topic><topic>Zika Virus - immunology</topic><topic>Zika Virus Infection - prevention & control</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Malafa, Stefan</creatorcontrib><creatorcontrib>Medits, Iris</creatorcontrib><creatorcontrib>Aberle, Judith H</creatorcontrib><creatorcontrib>Aberle, Stephan W</creatorcontrib><creatorcontrib>Haslwanter, Denise</creatorcontrib><creatorcontrib>Tsouchnikas, Georgios</creatorcontrib><creatorcontrib>Wölfel, Silke</creatorcontrib><creatorcontrib>Huber, Kristina L</creatorcontrib><creatorcontrib>Percivalle, Elena</creatorcontrib><creatorcontrib>Cherpillod, Pascal</creatorcontrib><creatorcontrib>Thaler, Melissa</creatorcontrib><creatorcontrib>Roßbacher, Lena</creatorcontrib><creatorcontrib>Kundi, Michael</creatorcontrib><creatorcontrib>Heinz, Franz X</creatorcontrib><creatorcontrib>Stiasny, Karin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Public Health Database</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 3: Aquatic Pollution & Environmental Quality</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals (DOAJ)</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Malafa, Stefan</au><au>Medits, Iris</au><au>Aberle, Judith H</au><au>Aberle, Stephan W</au><au>Haslwanter, Denise</au><au>Tsouchnikas, Georgios</au><au>Wölfel, Silke</au><au>Huber, Kristina L</au><au>Percivalle, Elena</au><au>Cherpillod, Pascal</au><au>Thaler, Melissa</au><au>Roßbacher, Lena</au><au>Kundi, Michael</au><au>Heinz, Franz X</au><au>Stiasny, Karin</au><au>Gubler, Duane J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of flavivirus vaccine-induced immunity on primary Zika virus antibody response in humans</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2020-02-01</date><risdate>2020</risdate><volume>14</volume><issue>2</issue><spage>e0008034</spage><epage>e0008034</epage><pages>e0008034-e0008034</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Zika virus has recently spread to South- and Central America, causing congenital birth defects and neurological complications. Many people at risk are flavivirus pre-immune due to prior infections with other flaviviruses (e.g. dengue virus) or flavivirus vaccinations. Since pre-existing cross-reactive immunity can potentially modulate antibody responses to Zika virus infection and may affect the outcome of disease, we analyzed fine-specificity as well as virus-neutralizing and infection-enhancing activities of antibodies induced by a primary Zika virus infection in flavivirus-naïve as well as yellow fever- and/or tick-borne encephalitis-vaccinated individuals.
Antibodies in sera from convalescent Zika patients with and without vaccine-induced immunity were assessed by ELISA with respect to Zika virus-specificity and flavivirus cross-reactivity. Functional analyses included virus neutralization and infection-enhancement. The contribution of IgM and cross-reactive antibodies to these properties was determined by depletion experiments.
Pre-existing flavivirus immunity had a strong influence on the antibody response in primary Zika virus infections, resulting in higher titers of broadly flavivirus cross-reactive antibodies and slightly lower levels of Zika virus-specific IgM. Antibody-dependent enhancement (ADE) of Zika virus was mediated by sub-neutralizing concentrations of specific IgG but not by cross-reactive antibodies. This effect was potently counteracted by the presence of neutralizing IgM. Broadly cross-reactive antibodies were able to both neutralize and enhance infection of dengue virus but not Zika virus, indicating a different exposure of conserved sequence elements in the two viruses.
Our data point to an important role of flavivirus-specific IgM during the transient early stages of infection, by contributing substantially to neutralization and by counteracting ADE. In addition, our results highlight structural differences between strains of Zika and dengue viruses that are used for analyzing infection-enhancement by cross-reactive antibodies. These findings underscore the possible impact of specific antibody patterns on flavivirus disease and vaccination efficacy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32017766</pmid><doi>10.1371/journal.pntd.0008034</doi><orcidid>https://orcid.org/0000-0002-1902-8674</orcidid><orcidid>https://orcid.org/0000-0002-7191-4331</orcidid><orcidid>https://orcid.org/0000-0002-0222-9832</orcidid><orcidid>https://orcid.org/0000-0002-2707-3213</orcidid><orcidid>https://orcid.org/0000-0003-2727-0468</orcidid><orcidid>https://orcid.org/0000-0003-3595-3074</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1935-2735 |
| ispartof | PLoS neglected tropical diseases, 2020-02, Vol.14 (2), p.e0008034-e0008034 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
| recordid | cdi_plos_journals_2377704975 |
| source | Directory of Open Access Journals (DOAJ); MEDLINE; Public Library of Science; PubMed Central; EZB Electronic Journals Library; PubMed Central Open Access |
| subjects | Analysis Antibodies Antibodies, Viral - blood Antibody Affinity Antibody response Antigens, Viral - immunology Biology and life sciences Birth defects Complications Complications and side effects Congenital defects Conserved sequence Cross-reactivity Data points Defects Dengue Dengue fever Dengue virus Depletion Disease control Diseases ELISA Encephalitis Enzyme-Linked Immunosorbent Assay Epidemics Epidemiology Genetic disorders Guillain-Barre syndrome Human diseases Humans Immunity Immunoglobulin G Immunoglobulin G - blood Immunoglobulin M Immunoglobulins Infection Infections Laboratories Medical research Medicine Medicine and Health Sciences Microbiological strains Neurological complications Neutralization Neutralization Tests Neutralizing Polyethylene Glycols Research and Analysis Methods Scientific equipment industry Specificity Strains Tick-borne diseases Tick-borne encephalitis Tropical diseases Vaccination Vaccines Vector-borne diseases Viral Envelope Proteins - immunology Viral Vaccines - immunology Virology Virus diseases Viruses West Nile virus Yellow fever Zika virus Zika Virus - genetics Zika Virus - immunology Zika Virus Infection - prevention & control |
| title | Impact of flavivirus vaccine-induced immunity on primary Zika virus antibody response in humans |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T16%3A45%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Impact%20of%20flavivirus%20vaccine-induced%20immunity%20on%20primary%20Zika%20virus%20antibody%20response%20in%20humans&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Malafa,%20Stefan&rft.date=2020-02-01&rft.volume=14&rft.issue=2&rft.spage=e0008034&rft.epage=e0008034&rft.pages=e0008034-e0008034&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0008034&rft_dat=%3Cgale_plos_%3EA616524927%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2377704975&rft_id=info:pmid/32017766&rft_galeid=A616524927&rft_doaj_id=oai_doaj_org_article_bbf59a1e7b4047f08c1dfe73e89850ce&rfr_iscdi=true |