Cargando…

Simultaneous Immunization with Multivalent Norovirus VLPs Induces Better Protective Immune Responses to Norovirus than Sequential Immunization

Human noroviruses (NoVs) are a genetically diverse, constantly evolving group of viruses. Here, we studied the effect of NoV pre-existing immunity on the success of NoV vaccinations with genetically close and distant genotypes. A sequential immunization as an alternative approach to multivalent NoV...

Descripción completa

Detalles Bibliográficos
Autores principales: Malm, Maria, Vesikari, Timo, Blazevic, Vesna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893631/
https://www.ncbi.nlm.nih.gov/pubmed/31684058
http://dx.doi.org/10.3390/v11111018
_version_ 1783476244056113152
author Malm, Maria
Vesikari, Timo
Blazevic, Vesna
author_facet Malm, Maria
Vesikari, Timo
Blazevic, Vesna
author_sort Malm, Maria
collection PubMed
description Human noroviruses (NoVs) are a genetically diverse, constantly evolving group of viruses. Here, we studied the effect of NoV pre-existing immunity on the success of NoV vaccinations with genetically close and distant genotypes. A sequential immunization as an alternative approach to multivalent NoV virus-like particles (VLPs) vaccine was investigated. Mice were immunized with NoV GI.3, GII.4-1999, GII.17, and GII.4 Sydney as monovalent VLPs or as a single tetravalent mixture combined with rotavirus VP6-protein. Sequentially immunized mice were primed with a trivalent vaccine candidate (GI.3 + GII.4-1999 + VP6) and boosted, first with GII.17 and then with GII.4 Sydney VLPs. NoV serum antibodies were analyzed. Similar NoV genotype-specific immune responses were induced with the monovalent and multivalent mixture immunizations, and no immunological interference was observed. Multivalent immunization with simultaneous mix was found to be superior to sequential immunization, as sequential boost induced strong blocking antibody response against the distant genotype (GII.17), but not against GII.4 Sydney, closely related to GII.4-1999, contained in the priming vaccine. Genetically close antigens may interfere with the immune response generation and thereby immune responses may be differently formed depending on the degree of NoV VLP genotype identity.
format Online
Article
Text
id pubmed-6893631
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68936312019-12-23 Simultaneous Immunization with Multivalent Norovirus VLPs Induces Better Protective Immune Responses to Norovirus than Sequential Immunization Malm, Maria Vesikari, Timo Blazevic, Vesna Viruses Article Human noroviruses (NoVs) are a genetically diverse, constantly evolving group of viruses. Here, we studied the effect of NoV pre-existing immunity on the success of NoV vaccinations with genetically close and distant genotypes. A sequential immunization as an alternative approach to multivalent NoV virus-like particles (VLPs) vaccine was investigated. Mice were immunized with NoV GI.3, GII.4-1999, GII.17, and GII.4 Sydney as monovalent VLPs or as a single tetravalent mixture combined with rotavirus VP6-protein. Sequentially immunized mice were primed with a trivalent vaccine candidate (GI.3 + GII.4-1999 + VP6) and boosted, first with GII.17 and then with GII.4 Sydney VLPs. NoV serum antibodies were analyzed. Similar NoV genotype-specific immune responses were induced with the monovalent and multivalent mixture immunizations, and no immunological interference was observed. Multivalent immunization with simultaneous mix was found to be superior to sequential immunization, as sequential boost induced strong blocking antibody response against the distant genotype (GII.17), but not against GII.4 Sydney, closely related to GII.4-1999, contained in the priming vaccine. Genetically close antigens may interfere with the immune response generation and thereby immune responses may be differently formed depending on the degree of NoV VLP genotype identity. MDPI 2019-11-02 /pmc/articles/PMC6893631/ /pubmed/31684058 http://dx.doi.org/10.3390/v11111018 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Malm, Maria
Vesikari, Timo
Blazevic, Vesna
Simultaneous Immunization with Multivalent Norovirus VLPs Induces Better Protective Immune Responses to Norovirus than Sequential Immunization
title Simultaneous Immunization with Multivalent Norovirus VLPs Induces Better Protective Immune Responses to Norovirus than Sequential Immunization
title_full Simultaneous Immunization with Multivalent Norovirus VLPs Induces Better Protective Immune Responses to Norovirus than Sequential Immunization
title_fullStr Simultaneous Immunization with Multivalent Norovirus VLPs Induces Better Protective Immune Responses to Norovirus than Sequential Immunization
title_full_unstemmed Simultaneous Immunization with Multivalent Norovirus VLPs Induces Better Protective Immune Responses to Norovirus than Sequential Immunization
title_short Simultaneous Immunization with Multivalent Norovirus VLPs Induces Better Protective Immune Responses to Norovirus than Sequential Immunization
title_sort simultaneous immunization with multivalent norovirus vlps induces better protective immune responses to norovirus than sequential immunization
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893631/
https://www.ncbi.nlm.nih.gov/pubmed/31684058
http://dx.doi.org/10.3390/v11111018
work_keys_str_mv AT malmmaria simultaneousimmunizationwithmultivalentnorovirusvlpsinducesbetterprotectiveimmuneresponsestonorovirusthansequentialimmunization
AT vesikaritimo simultaneousimmunizationwithmultivalentnorovirusvlpsinducesbetterprotectiveimmuneresponsestonorovirusthansequentialimmunization
AT blazevicvesna simultaneousimmunizationwithmultivalentnorovirusvlpsinducesbetterprotectiveimmuneresponsestonorovirusthansequentialimmunization