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Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial
BACKGROUND: Human noroviruses (NoVs) are the primary cause of acute gastroenteritis and are characterized by antigenic variation between genogroups and genotypes and antigenic drift of strains within the predominant GII.4 genotype. In the context of this diversity, an effective NoV vaccine must elic...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371888/ https://www.ncbi.nlm.nih.gov/pubmed/25803642 http://dx.doi.org/10.1371/journal.pmed.1001807 |
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author | Lindesmith, Lisa C. Ferris, Martin T. Mullan, Clancy W. Ferreira, Jennifer Debbink, Kari Swanstrom, Jesica Richardson, Charles Goodwin, Robert R. Baehner, Frank Mendelman, Paul M. Bargatze, Robert F. Baric, Ralph S. |
author_facet | Lindesmith, Lisa C. Ferris, Martin T. Mullan, Clancy W. Ferreira, Jennifer Debbink, Kari Swanstrom, Jesica Richardson, Charles Goodwin, Robert R. Baehner, Frank Mendelman, Paul M. Bargatze, Robert F. Baric, Ralph S. |
author_sort | Lindesmith, Lisa C. |
collection | PubMed |
description | BACKGROUND: Human noroviruses (NoVs) are the primary cause of acute gastroenteritis and are characterized by antigenic variation between genogroups and genotypes and antigenic drift of strains within the predominant GII.4 genotype. In the context of this diversity, an effective NoV vaccine must elicit broadly protective immunity. We used an antibody (Ab) binding blockade assay to measure the potential cross-strain protection provided by a multivalent NoV virus-like particle (VLP) candidate vaccine in human volunteers. METHODS AND FINDINGS: Sera from ten human volunteers immunized with a multivalent NoV VLP vaccine (genotypes GI.1/GII.4) were analyzed for IgG and Ab blockade of VLP interaction with carbohydrate ligand, a potential correlate of protective immunity to NoV infection and illness. Immunization resulted in rapid rises in IgG and blockade Ab titers against both vaccine components and additional VLPs representing diverse strains and genotypes not represented in the vaccine. Importantly, vaccination induced blockade Ab to two novel GII.4 strains not in circulation at the time of vaccination or sample collection. GII.4 cross-reactive blockade Ab titers were more potent than responses against non-GII.4 VLPs, suggesting that previous exposure history to this dominant circulating genotype may impact the vaccine Ab response. Further, antigenic cartography indicated that vaccination preferentially activated preexisting Ab responses to epitopes associated with GII.4.1997. Study interpretations may be limited by the relevance of the surrogate neutralization assay and the number of immunized participants evaluated. CONCLUSIONS: Vaccination with a multivalent NoV VLP vaccine induces a broadly blocking Ab response to multiple epitopes within vaccine and non-vaccine NoV strains and to novel antigenic variants not yet circulating at the time of vaccination. These data reveal new information about complex NoV immune responses to both natural exposure and to vaccination, and support the potential feasibility of an efficacious multivalent NoV VLP vaccine for future use in human populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT01168401 |
format | Online Article Text |
id | pubmed-4371888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43718882015-04-04 Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial Lindesmith, Lisa C. Ferris, Martin T. Mullan, Clancy W. Ferreira, Jennifer Debbink, Kari Swanstrom, Jesica Richardson, Charles Goodwin, Robert R. Baehner, Frank Mendelman, Paul M. Bargatze, Robert F. Baric, Ralph S. PLoS Med Research Article BACKGROUND: Human noroviruses (NoVs) are the primary cause of acute gastroenteritis and are characterized by antigenic variation between genogroups and genotypes and antigenic drift of strains within the predominant GII.4 genotype. In the context of this diversity, an effective NoV vaccine must elicit broadly protective immunity. We used an antibody (Ab) binding blockade assay to measure the potential cross-strain protection provided by a multivalent NoV virus-like particle (VLP) candidate vaccine in human volunteers. METHODS AND FINDINGS: Sera from ten human volunteers immunized with a multivalent NoV VLP vaccine (genotypes GI.1/GII.4) were analyzed for IgG and Ab blockade of VLP interaction with carbohydrate ligand, a potential correlate of protective immunity to NoV infection and illness. Immunization resulted in rapid rises in IgG and blockade Ab titers against both vaccine components and additional VLPs representing diverse strains and genotypes not represented in the vaccine. Importantly, vaccination induced blockade Ab to two novel GII.4 strains not in circulation at the time of vaccination or sample collection. GII.4 cross-reactive blockade Ab titers were more potent than responses against non-GII.4 VLPs, suggesting that previous exposure history to this dominant circulating genotype may impact the vaccine Ab response. Further, antigenic cartography indicated that vaccination preferentially activated preexisting Ab responses to epitopes associated with GII.4.1997. Study interpretations may be limited by the relevance of the surrogate neutralization assay and the number of immunized participants evaluated. CONCLUSIONS: Vaccination with a multivalent NoV VLP vaccine induces a broadly blocking Ab response to multiple epitopes within vaccine and non-vaccine NoV strains and to novel antigenic variants not yet circulating at the time of vaccination. These data reveal new information about complex NoV immune responses to both natural exposure and to vaccination, and support the potential feasibility of an efficacious multivalent NoV VLP vaccine for future use in human populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT01168401 Public Library of Science 2015-03-24 /pmc/articles/PMC4371888/ /pubmed/25803642 http://dx.doi.org/10.1371/journal.pmed.1001807 Text en © 2015 Lindesmith et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lindesmith, Lisa C. Ferris, Martin T. Mullan, Clancy W. Ferreira, Jennifer Debbink, Kari Swanstrom, Jesica Richardson, Charles Goodwin, Robert R. Baehner, Frank Mendelman, Paul M. Bargatze, Robert F. Baric, Ralph S. Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial |
title | Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial |
title_full | Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial |
title_fullStr | Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial |
title_full_unstemmed | Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial |
title_short | Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial |
title_sort | broad blockade antibody responses in human volunteers after immunization with a multivalent norovirus vlp candidate vaccine: immunological analyses from a phase i clinical trial |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371888/ https://www.ncbi.nlm.nih.gov/pubmed/25803642 http://dx.doi.org/10.1371/journal.pmed.1001807 |
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