Efficacy of an intramuscular bivalent norovirus GI.1/GII.4 virus-like particle vaccine candidate in healthy US adults

Sherwood, James R.; Mendelman, Paul M.; Lloyd, Elisabeth A.; Liu, Mengya; Boslego, John W.; Borkowski, Astrid; Jackson, Ashley; Faix, Dennis J.

doi:10.1016/j.vaccine.2020.07.069

Cited by 55 publications

(42 citation statements)

References 13 publications

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“…At present, the main epidemic strains of NoVs are Sydney_2012 of GII.4, variant A of GII.2, genotype GII.3 and variant B and C of GII.6, as well as variant D of GII.17. The mean amino acid distances among these main epidemic strains and the vaccine strain GII.4c of a vaccine candidate that is currently under a phase IIb clinical trial [ 17 ] were calculated ( Table 3 ). The vaccine strain GII.4c is closest to Sydney_2012 of GII.4 (0.053) but further away from the other epidemic strains of heterologous genotypes (0.319–0.354).…”

Section: Resultsmentioning

confidence: 99%

“…At present, the cross-protection between genotypes/variants and whether a candidate vaccine will induce a broad spectrum of immunity remain unknown. The notion that epitopes A (294, 296–298, 368, 372) and E (407, 412–413) of the currently prevalent GII.4 variant Sydney_2012 are distinct from those of the vaccine strain GII.4c raises concerns about the potential lacking of cross-protection the candidate vaccine that is currently under phase IIb clinical trial [ 17 ]. Previous studies showed that epitope A likely formed a non-contiguous, conformational epitope that changed over time, suggesting its important role associated with immune escape [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, a recent study has demonstrated that the levels of HBGA-blocking antibodies and Pan-Ig induced by the GII.4c VLPs were increased in some placebo acute gastroenteritis (AGE) cases infected with GII.2. These findings suggested the vaccine strain GII.4c may possess a certain degree of cross-protection to other genotypes within the same genogroup [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

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Prevalence and Evolution of Noroviruses between 1966 and 2019, Implications for Vaccine Design

et al. 2021

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Noroviruses (NoVs), a group of single-stranded RNA viruses causing epidemic acute gastroenteritis in humans, are highly diverse, consisting of multiple genogroups with >30 genotypes. Their continual evolutions make NoV vaccine design and development difficult. Here, we report a study of NoV sequences obtained from a population-based diarrhea surveillance in Zhengding County of Hebei Province spanning from 2001 to 2019 and those available in the GenBank database from 1966 to 2019. NoV genotypes and/or variants that may evade immunity were screened and identified based on primary and conformational structures for vaccine design. We selected 366, 301, 139, 74 and 495 complete VP1-coding nucleotide sequences representing the predominant genotypes of GII.4, GII.2, GII.3, GII.6 and GII.17, respectively. A total of 16 distinct GII.4 variants were identified, showing a typical linear evolutionary pattern of variant replacement, while only 1–4 variants of the other genotypes were found to co-circulate over the 40–50-year period without typical variant replacement. The vaccine strain GII.4c is close to variant Sydney_2012 (0.053) in their primary structure, but they are distinct at epitopes A and E in conformations. Our data suggested GII.4 variant Sydney_2012, GII.2 variant A, a GII.3 strain, GII.6 variants B and C and GII.17 variant D are primary candidate strains for NoV vaccine development.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Prevalence and Evolution of Noroviruses between 1966 and 2019, Implications for Vaccine Design

et al. 2021

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“…A bivalent (GI.1, GII.4) NoV vaccine study in healthy US adults described cross-protection to GII.2, but there are limited data overall on cross-protection to different circulating NoV strains as well as duration of protection [ 124 ]. Nitazoxanide and oral immunoglobulin need further study to determine efficacy, and it is unclear whether differences in treatment outcomes correlate with virus genotype or viral load.…”

Section: Areas Of Uncertaintymentioning

confidence: 99%

Norovirus in Cancer Patients: A Review

Kondapi

Ramani

Estes

et al. 2021

Open Forum Infectious Diseases

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Norovirus (NoV) is the leading cause of viral-related diarrhea in cancer patients in whom it can be chronic, contributing to a decreased quality of life, interruption of cancer care, malnutrition, and altered mucosal barrier function. Immunosuppressed cancer patients shed NoV for longer periods of time than immunocompetent hosts favoring quasispecies development and emergence of novel NoV variants. While nucleic acid amplification tests (NAATs) for NoV diagnosis have revolutionized our understanding of NoV burden of disease; not all NAATs provide information on viral load, or infecting genotype. There is currently no effective antiviral or vaccine for chronic NoV infections. Screening for inhibitors of NoV replication in intestinal organoid culture models and creation of NoV specific adoptive T cells are promising new strategies to develop treatments for chronic NoV in immunosuppressed patients. Herein we summarize data on the epidemiology, clinical manifestations, diagnostic challenges and treatment of NoV infection in patients with cancer.

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“…HuNoVs have great genetic diversity with many genotypes infecting humans, GII.4 noroviruses are the most prevalent particularly in large outbreak settings, and linked to the highest mortality and hospitalization rates over the last years [ 21 ]. Efforts to develop a HuNoV vaccine are ongoing with the most advanced candidates being developed by Takeda, in phase IIb of clinical development [ 22 ], and Vaxart, in phase Ib [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Current and Future Antiviral Strategies to Tackle Gastrointestinal Viral Infections

et al. 2021

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Acute gastroenteritis caused by virus has a major impact on public health worldwide in terms of morbidity, mortality, and economic burden. The main culprits are rotaviruses, noroviruses, sapoviruses, astroviruses, and enteric adenoviruses. Currently, there are no antiviral drugs available for the prevention or treatment of viral gastroenteritis. Here, we describe the antivirals that were identified as having in vitro and/or in vivo activity against these viruses, originating from in silico design or library screening, natural sources or being repurposed drugs. We also highlight recent advances in model systems available for this (hard to cultivate) group of viruses, such as organoid technologies, and that will facilitate antiviral studies as well as fill some of current knowledge gaps that hamper the development of highly efficient therapies against gastroenteric viruses.

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Efficacy of an intramuscular bivalent norovirus GI.1/GII.4 virus-like particle vaccine candidate in healthy US adults

Cited by 55 publications

References 13 publications

Prevalence and Evolution of Noroviruses between 1966 and 2019, Implications for Vaccine Design

Prevalence and Evolution of Noroviruses between 1966 and 2019, Implications for Vaccine Design

Norovirus in Cancer Patients: A Review

Current and Future Antiviral Strategies to Tackle Gastrointestinal Viral Infections

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