Trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.

Rotavirus (RV) and norovirus (NoV) are the two major causes of viral gastroenteritis (GE) in children worldwide. We have developed an injectable vaccine design to prevent infection or GE induced with these enteric viruses. The trivalent combination vaccine consists of NoV capsid (VP1) derived virus-...

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Autores principales: Kirsi Tamminen, Suvi Lappalainen, Leena Huhti, Timo Vesikari, Vesna Blazevic
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:0a2fd7021a5c4fbaa47aaf7d860cd5312021-11-18T09:02:34ZTrivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.1932-620310.1371/journal.pone.0070409https://doaj.org/article/0a2fd7021a5c4fbaa47aaf7d860cd5312013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23922988/?tool=EBIhttps://doaj.org/toc/1932-6203Rotavirus (RV) and norovirus (NoV) are the two major causes of viral gastroenteritis (GE) in children worldwide. We have developed an injectable vaccine design to prevent infection or GE induced with these enteric viruses. The trivalent combination vaccine consists of NoV capsid (VP1) derived virus-like particles (VLPs) of GI-3 and GII-4 representing the two major NoV genogroups and tubular RV recombinant VP6 (rVP6), the most conserved and abundant RV protein. Each component was produced in insect cells by a recombinant baculovirus expression system and combined in vitro. The vaccine components were administered intramuscularly to BALB/c mice either separately or in the trivalent combination. High levels of NoV and RV type specific serum IgGs with high avidity (>50%) as well as intestinal IgGs were detected in the immunized mice. Cross-reactive IgG antibodies were also elicited against heterologous NoV VLPs not used for immunization (GII-4 NO, GII-12 and GI-1 VLPs) and to different RVs from cell cultures. NoV-specific serum antibodies blocked binding of homologous and heterologous VLPs to the putative receptors, histo-blood group antigens, suggesting broad NoV neutralizing activity of the sera. Mucosal antibodies of mice immunized with the trivalent combination vaccine inhibited RV infection in vitro. In addition, cross-reactive T cell immune responses to NoV and RV-specific antigens were detected. All the responses were sustained for up to six months. No mutual inhibition of the components in the trivalent vaccine combination was observed. In conclusion, the NoV GI and GII VLPs combination induced broader cross-reactive and potentially neutralizing immune responses than either of the VLPs alone. Therefore, trivalent vaccine might induce protective immune responses to the vast majority of circulating NoV and RV genotypes.Kirsi TamminenSuvi LappalainenLeena HuhtiTimo VesikariVesna BlazevicPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e70409 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kirsi Tamminen
Suvi Lappalainen
Leena Huhti
Timo Vesikari
Vesna Blazevic
Trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.
description Rotavirus (RV) and norovirus (NoV) are the two major causes of viral gastroenteritis (GE) in children worldwide. We have developed an injectable vaccine design to prevent infection or GE induced with these enteric viruses. The trivalent combination vaccine consists of NoV capsid (VP1) derived virus-like particles (VLPs) of GI-3 and GII-4 representing the two major NoV genogroups and tubular RV recombinant VP6 (rVP6), the most conserved and abundant RV protein. Each component was produced in insect cells by a recombinant baculovirus expression system and combined in vitro. The vaccine components were administered intramuscularly to BALB/c mice either separately or in the trivalent combination. High levels of NoV and RV type specific serum IgGs with high avidity (>50%) as well as intestinal IgGs were detected in the immunized mice. Cross-reactive IgG antibodies were also elicited against heterologous NoV VLPs not used for immunization (GII-4 NO, GII-12 and GI-1 VLPs) and to different RVs from cell cultures. NoV-specific serum antibodies blocked binding of homologous and heterologous VLPs to the putative receptors, histo-blood group antigens, suggesting broad NoV neutralizing activity of the sera. Mucosal antibodies of mice immunized with the trivalent combination vaccine inhibited RV infection in vitro. In addition, cross-reactive T cell immune responses to NoV and RV-specific antigens were detected. All the responses were sustained for up to six months. No mutual inhibition of the components in the trivalent vaccine combination was observed. In conclusion, the NoV GI and GII VLPs combination induced broader cross-reactive and potentially neutralizing immune responses than either of the VLPs alone. Therefore, trivalent vaccine might induce protective immune responses to the vast majority of circulating NoV and RV genotypes.
format article
author Kirsi Tamminen
Suvi Lappalainen
Leena Huhti
Timo Vesikari
Vesna Blazevic
author_facet Kirsi Tamminen
Suvi Lappalainen
Leena Huhti
Timo Vesikari
Vesna Blazevic
author_sort Kirsi Tamminen
title Trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.
title_short Trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.
title_full Trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.
title_fullStr Trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.
title_full_unstemmed Trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.
title_sort trivalent combination vaccine induces broad heterologous immune responses to norovirus and rotavirus in mice.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/0a2fd7021a5c4fbaa47aaf7d860cd531
work_keys_str_mv AT kirsitamminen trivalentcombinationvaccineinducesbroadheterologousimmuneresponsestonorovirusandrotavirusinmice
AT suvilappalainen trivalentcombinationvaccineinducesbroadheterologousimmuneresponsestonorovirusandrotavirusinmice
AT leenahuhti trivalentcombinationvaccineinducesbroadheterologousimmuneresponsestonorovirusandrotavirusinmice
AT timovesikari trivalentcombinationvaccineinducesbroadheterologousimmuneresponsestonorovirusandrotavirusinmice
AT vesnablazevic trivalentcombinationvaccineinducesbroadheterologousimmuneresponsestonorovirusandrotavirusinmice
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