A phase 2 study of the bivalent VLP norovirus vaccine candidate in older adults; impact of MPL adjuvant or a second dose

Treanor, John; Sherwood, Jim; Cramer, Jakob P.; Bouveret, Nancy; Lin, Stella; Baehner, Frank; Borkowski, Astrid; investigators, Nor

doi:10.1016/j.vaccine.2020.06.011

Cited by 25 publications

(28 citation statements)

References 27 publications

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“…Recent in vivo and in vitro findings have added to the understanding of host immunity in response to norovirus infection [ 272 , 273 , 274 ]. While neither approved vaccines nor small molecule treatments are yet available, vaccine development has progressed to preclinical and even clinical trial testing of candidates [ 281 , 306 , 307 , 308 ] and ongoing development of therapeutic agents includes promising direct-acting small molecules and host-factor drugs [ 145 , 292 , 296 , 302 ]. Many of these discoveries have been facilitated by novel in vitro and in vivo culture systems that have inspired fascinating new avenues of norovirus research.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the lack of a universally accepted correlate of protection against norovirus, documented varying seroresponse and uncertainty regarding the duration of long-term immunity conferred by norovirus infection or vaccination are barriers faced in norovirus vaccine development [ 305 ]. Nevertheless, a bivalent GI.1/GII.4 VLP vaccine [ 306 ] and a recombinant adenovirus vector vaccine expressing GI.1 or GII.4 VP1 with monovalent or bivalent dosing [ 307 ], are currently in clinical trials. Further vaccines have been approved for clinical trial testing or are in the preclinical phase of development [ 281 , 308 ].…”

Section: Treatment and Prophylaxismentioning

confidence: 99%

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Noroviruses—The State of the Art, Nearly Fifty Years after Their Initial Discovery

Ludwig‐Begall

Mauroy

Thiry

2021

Viruses

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Human noroviruses are recognised as the major global cause of viral gastroenteritis. Here, we provide an overview of notable advances in norovirus research and provide a short recap of the novel model systems to which much of the recent progress is owed. Significant advances include an updated classification system, the description of alternative virus-like protein morphologies and capsid dynamics, and the further elucidation of the functions and roles of various viral proteins. Important milestones include new insights into cell tropism, host and microbial attachment factors and receptors, interactions with the cellular translational apparatus, and viral egress from cells. Noroviruses have been detected in previously unrecognised hosts and detection itself is facilitated by improved analytical techniques. New potential transmission routes and/or viral reservoirs have been proposed. Recent in vivo and in vitro findings have added to the understanding of host immunity in response to norovirus infection, and vaccine development has progressed to preclinical and even clinical trial testing. Ongoing development of therapeutics includes promising direct-acting small molecules and host-factor drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Treatment and Prophylaxismentioning

confidence: 99%

Noroviruses—The State of the Art, Nearly Fifty Years after Their Initial Discovery

Ludwig‐Begall

Mauroy

Thiry

2021

Viruses

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“…A number of preclinical and clinical trial studies revealed that HuNoV vaccines were able to induce good immune responses [ 39 , 44 , 46 , 47 , 48 , 50 , 51 , 54 , 55 , 56 , 57 , 58 , 59 , 61 , 64 , 65 , 66 , 67 , 68 , 70 , 71 , 72 , 74 , 75 , 76 , 77 , 78 , 79 ]. Regarding protective immunity, one vaccine efficacy study in gnotobiotic pigs showed that adjuvanted HuNoV VLPs increased protection rates against viral shedding and diarrhea after the immunized animals were challenged with the homologous HuNoV genotype [ 80 ].…”

Section: Discussionmentioning

confidence: 99%

“…Whether such immune responses could confer protection remains unclear. A phase II study regarding immunogenicity and safety of the bivalent HuNoV VLP vaccine candidate in >60-year-olds was completed [ 70 ], showing that the elderly displayed no safety concerns and had similar immune responses to the vaccine candidate as the younger cohorts. Further clinical phase II trials regarding efficacy and long-term immunogenicity in adults are ongoing.…”

Section: Advances Of Hunov Vaccine Developmentmentioning

confidence: 99%

Advances in Human Norovirus Vaccine Research

Zhang

2021

Vaccines

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Human norovirus (HuNoV) is the leading cause of acute gastroenteritis (AGE) worldwide, which is highly stable and contagious, with a few virus particles being sufficient to establish infection. Although the World Health Organization in 2016 stated that it should be an absolute priority to develop a HuNoV vaccine, unfortunately, there is currently no licensed HuNoV vaccine available. The major barrier to the development of an effective HuNoV vaccine is the lack of a robust and reproducible in vitro cultivation system. To develop a HuNoV vaccine, HuNoV immunogen alone or in combination with other viral immunogens have been designed to assess whether they can simultaneously induce protective immune responses against different viruses. Additionally, monovalent and multivalent vaccines from different HuNoV genotypes, including GI and GII HuNoV virus-like particles (VLPs), have been assessed in order to induce broad protection. Although there are several HuNoV vaccine candidates based on VLPs that are being tested in clinical trials, the challenges to develop effective HuNoV vaccines remain largely unresolved. In this review, we summarize the advances of the HuNoV cultivation system and HuNoV vaccine research and discuss current challenges and future perspectives in HuNoV vaccine development.

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“…There is still no licensed vaccine against norovirus made available. However, there are few promising candidates in the pipeline with one already in phase 2 [18]. In addition, efforts in developing norovirus-specific antiviral drugs are also ongoing.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms for Norovirus Genome Replication

Yunus¹

2021

Norovirus

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The genomes of positive strand RNA viruses often contain more than one open reading frame. Some of these viruses have evolved novel mechanisms to regulate the synthesis of the other open reading frames that in some cases involved the production of a subgenomic RNA or RNAs. Very often, the presence of the subgenomic RNA is used as indicator for active viral genome replication. Norovirus, a major cause for gastroenteritis as well as with all other caliciviruses follow a typical positive strand RNA viruses genome replication strategy. In addition, noroviruses also produce a subgenomic RNA during their replication in infected cells. Efficient and adequate synthesis of norovirus subgenomic RNA is crucial for successful viral replication and productive infection leading to the generation of infectious viral progeny. This chapter will dissect the significant findings on mechanisms involved in norovirus genome replication as well as focusing on subgenomic RNA production.

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A phase 2 study of the bivalent VLP norovirus vaccine candidate in older adults; impact of MPL adjuvant or a second dose

Cited by 25 publications

References 27 publications

Noroviruses—The State of the Art, Nearly Fifty Years after Their Initial Discovery

Noroviruses—The State of the Art, Nearly Fifty Years after Their Initial Discovery

Advances in Human Norovirus Vaccine Research

Molecular Mechanisms for Norovirus Genome Replication

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