Norovirus vaccines under development

Lucero, Yalda; Vidal, Roberto; O’Ryan, Miguel

doi:10.1016/j.vaccine.2017.06.043

Cited by 55 publications

(55 citation statements)

References 87 publications

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“…Current vaccine approaches consider GII.4 as a main NoV vaccine antigen (9,29), and therefore it is of interest to determine the level of GII.4 VLP-induced cross-reactive responses to GII.17. no.…”

Section: Introductionmentioning

confidence: 99%

Norovirus GII.17 Virus-Like Particles Bind to Different Histo-Blood Group Antigens and Cross-React with Genogroup II-Specific Mouse Sera

et al. 2018

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Majority of norovirus (NoV) outbreaks and sporadic infections in the past 20 years have been caused by GII.4 variants. In 2014, norovirus GII.17 genotype replaced GII.4 strains in several Asian countries and major outbreaks were reported in other continents. As GII.17 is a recently evolved NoV strain, there is a gap especially in immunogenicity data. In the present study we investigated GII.17 virus-like particle (VLP) binding to various cellular ligands, histo-blood group antigens (HBGAs), using human saliva, pig gastric mucin, and synthetic oligosaccharides as HBGA sources. The level of GII.17 immunological cross-reactivity was determined in mice immunized with different monovalent and multivalent NoV VLP compositions. Furthermore, healthy adult volunteers with natural NoV exposure history were analyzed for GII.17-specific seroresponses. The results showed that GII.17 Kawasaki VLPs bind to a wide range of HBGAs, even though fewer than GII.4 VLPs. Immunization of mice with a multivalent VLP formulation containing different genogroup II NoV VLPs was required to obtain the highest magnitude of cross-reactive binding antibodies to GII.17. However, co-immunization with different VLP genotypes did not improve potentially neutralizing antibodies to GII.17, which remained very moderate. Low pre-existing cross-reactive antibodies to GII.17 observed in human adults indicates the presence of a large pool of susceptible individuals in this population. These data suggest that GII.17 and alike newly emerging, distinct NoV genotypes should be considered as an antigenic component for vaccine formulations, which currently widely rely on GII.4-specific immunity.

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Section: Introductionmentioning

confidence: 99%

Norovirus GII.17 Virus-Like Particles Bind to Different Histo-Blood Group Antigens and Cross-React with Genogroup II-Specific Mouse Sera

et al. 2018

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“…Dazu gehören in allen Einrichtungen der Kranken-und Altenpflege praktikable Personalausfallkonzepte [26], die nicht nur eine Unterbrechung der Patientenversorgung verhindern, sondern auch fördern, dass NoV-infizierte Beschäftigte dem Arbeitsplatz die empfohlene Mindestdauer von 48 Stunden [30] ohne Verlust der Versorgungsqualität fernbleiben können. Ein Impfstoff befindet sich derzeit in der Erprobung [38]. Im Sinne des Arbeitsschutzes ist in Fall des Erprobungserfolgs auch die Indikation zu einer Impfempfehlung für exponierte Beschäftigte zu diskutieren.…”

Section: Diskussionunclassified

Zur statistischen Untererfassung von Norovirus-Infektionen: Erkenntnisse aus Daten von zwei Gesundheitsämtern

et al. 2020

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Zusammenfassung Hintergrund Seit 2011 müssen dem Robert Koch-Institut (RKI) nach dem Infektionsschutzgesetz (IfSG) regelhaft nur noch labordiagnostisch bestätigte Norovirus (NoV)-Gastroenteritisfälle, nicht aber z. B. klinisch- epidemiologische gemeldet werden, weshalb sich die ohnehin schon bestehende Untererfassung von NoV-Fällen in Deutschland deutlich verstärkt haben dürfte. Fragestellung Um das Ausmaß der Untererfassung zu diskutieren, wird in diesem Beitrag fallbeispielhaft dargestellt, inwieweit bei Gastroenteritisausbrüchen in Krankenhäusern und Gemeinschaftseinrichtungen überhaupt labordiagnostische Nachweise zur Klärung des Infektionsauslösers erfolgen. Interessant für die Abschätzung der arbeitsmedizinischen Bedeutung von NoV-Gastroenteritis ist auch der Anteil des erkrankten Personals. Material und Methoden Von allen pseudonymisierten Gastroenteritis-Ausbruchsdaten, die 2 lokalen Gesundheitsämtern zwischen 2011 und 2015 gemeldet wurden, wurde retrospektiv der Anteil labor-diagnostisch bestätigter NoV-Ausbrüche und -Fälle einschließlich gemeldeter Beschäftigter in Krankenhäusern und Gemeinschaftseinrichtungen (Altenpflegeheime, Kindertagesstätten, Schulen) errechnet. Ergebnisse Es wurde nur bei wenigen Gastroenteritisausbrüchen in Kindertagesstätten eine ätiologische Erregerabklärung durchgeführt, weshalb nur 6% und weniger als NoV-Ausbrüche klassifiziert werden konnten. In Altenpflegeheimen wurde rund die Hälfte der Ausbrüche NoV-klassifiziert, in Krankenhäusern fast alle. Beschäftigte machten bei NoV-Ausbrüchen bis zu 23% der Erkrankten aus. Schlussfolgerungen Der geringe Umfang labordiagnostischer Untersuchungen bei Gastroenteritisausbrüchen in Kindertagesstätten und Schulen impliziert eine erhebliche Anzahl an versteckten NoV-Fällen. Aufgrund des Anteils infizierter Beschäftigter in Ausbrüchen sollten NoV auch als arbeitsmedizinische Fragestellung stärker in den Fokus gerückt werden. Weitere, größer angelegte Prospektivstudien sind erforderlich, um diese ersten Erkenntnisse empirisch zu untermauern.

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“…3 Although parenteral vaccine delivery is more amenable and effective in inducing systemic IgG responses, the protective efficacy of vaccines against mucosal pathogens should be evaluated by the immune responses induced in effector mucosal sites. 27 Vaccination via the IN route provides desirable attributes such as easy administration, noninvasiveness, flexibility, and the ability to trigger the common mucosal immune responses in pulmonary, urogenital and gastrointestinal regions.…”

Section: Discussionmentioning

confidence: 99%

“…The absence of culture system and an appropriate animal model for NoVs hampers researches for vaccine development, pathogenesis, and diagnosis of the viruses. NoVs have highly diverse genomes and antigens as a consequence of frequent point mutation and recombination, 3 which is also responsible for the lack of effective vaccines and therapeutic agents to combat NoV infections.…”

Section: Introductionmentioning

confidence: 99%

More robust gut immune responses induced by combining intranasal and sublingual routes for prime-boost immunization

Hwang

Puth

Tan

et al. 2018

Human Vaccines & Immunotherapeutics

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Norovirus causes acute and debilitating gastroenteritis, characterized by vomiting and diarrhea. We recently reported a recombinant GII. 4 P domain particle (Pd) vaccine adjuvanted with a flagellin, Vibrio vulnificus FlaB, effectively promoting both humoral and cell-mediated immune responses. In the previous study, we found that sublingual (SL) immunization induced higher fecal secretory IgA (SIgA) responses while intranasal (IN) route provided higher amplitude of humoral and cellular immune responses in the systemic compartment. We hypothesized that the combination of IN and SL routes should induce more potent and sustained SIgA responses in the gut. In this study, we have tried combinatorial prime-boost immunization employing both IN and SL routes. The IN priming and SL boosting with the Pd+FlaB vaccine enhanced highest SIgA responses in feces, accompanying increased Pd-specific memory B cells and plasma cells in spleen and bone marrow, respectively. Notably, the strongest long-lasting SIgA response in feces was induced by combined IN prime and SL boost vaccination, which was sustained for more than 3 months. Significantly enhanced gut-homing B cell and follicular helper T cell responses in mesenteric lymph nodes (mLNs) were observed in the IN prime and SL boost combination. IN priming was a requisite for the robust induction of Pd-specific IFNγ, IL-2, IL-4 and IL-5 cytokine responses in the systemic immune compartment. Collectively, the IN prime and SL boost combination was the best option for inducing balanced long-lasting immune responses against the norovirus antigen in both enteric and systemic compartments. These results suggest that immune responses in specific mucosal compartments may be programmed by employing different prime-boost immunization routes.

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Norovirus vaccines under development

Cited by 55 publications

References 87 publications

Norovirus GII.17 Virus-Like Particles Bind to Different Histo-Blood Group Antigens and Cross-React with Genogroup II-Specific Mouse Sera

Norovirus GII.17 Virus-Like Particles Bind to Different Histo-Blood Group Antigens and Cross-React with Genogroup II-Specific Mouse Sera

Zur statistischen Untererfassung von Norovirus-Infektionen: Erkenntnisse aus Daten von zwei Gesundheitsämtern

More robust gut immune responses induced by combining intranasal and sublingual routes for prime-boost immunization

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