Mucosal Antibodies Induced by Intranasal but Not Intramuscular Immunization Block Norovirus GII.4 Virus-Like Particle Receptor Binding

2016 ◽  
Vol 29 (5) ◽  
pp. 315-319 ◽  
Author(s):  
Kirsi Tamminen ◽  
Maria Malm ◽  
Timo Vesikari ◽  
Vesna Blazevic
Keyword(s):  
Receptor Binding ◽  
Virus Like Particle ◽  
Norovirus Gii

scholarly journals A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Tiong Kit Tan ◽  
Pramila Rijal ◽  
Rolle Rahikainen ◽  
Anthony H. Keeble ◽  
Lisa Schimanski ◽  
...  
Keyword(s):  
Antibody Response ◽  
Receptor Binding ◽  
Binding Domain ◽  
Cold Chain ◽  
Receptor Binding Domain ◽  
Cell Infection ◽  
Protein Receptor ◽  
Virus Like Particle ◽  
Human Sera ◽  
Escape Mutants

AbstractThere is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine against SARS-CoV-2. The vaccine is based on the display of coronavirus spike glycoprotein receptor-binding domain (RBD) on a synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses of RBD-SpyVLP in a prime-boost regimen induce a strong neutralising antibody response in mice and pigs that is superior to convalescent human sera. We evaluate antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we show that RBD-SpyVLP induces a polyclonal antibody response that recognises key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. Moreover, RBD-SpyVLP is thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence. The data suggests that RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic.

scholarly journals Parenterally Administered Norovirus GII.4 Virus-Like Particle Vaccine Formulated with Aluminum Hydroxide or Monophosphoryl Lipid A Adjuvants Induces Systemic but Not Mucosal Immune Responses in Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Suvi Heinimäki ◽  
Maria Malm ◽  
Timo Vesikari ◽  
Vesna Blazevic
Keyword(s):  
Aluminum Hydroxide ◽  
Mucosal Immunity ◽  
Lipid A ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Virus Like Particle ◽  
Iga Antibodies ◽  
Nasal Secretions ◽  
Sparing Effect ◽  
Norovirus Gii

Norovirus (NoV) is a main cause of acute gastroenteritis across all ages worldwide. NoV vaccine candidates currently in clinical trials are based on noninfectious highly immunogenic virus-like particles (VLPs) delivered intramuscularly (IM). Since NoV is an enteric pathogen, it is likely that mucosal immunity has a significant role in protection from infection in the intestine. Due to the fact that IM delivery of NoV VLPs does not generate mucosal immunity, we investigated whether NoV genotype GII.4 VLPs coadministered with aluminum hydroxide (Al(OH)3) or monophosphoryl lipid A (MPLA) would induce mucosal antibodies in mice. Systemic as well as mucosal IgG and IgA antibodies in serum and intestinal and nasal secretions were measured. As expected, strong serum IgG, IgG1, and IgG2a antibodies as well as a dose sparing effect were induced by both Al(OH)3and MPLA, but no mucosal IgA antibodies were detected. In contrast, IN immunization with GII.4 VLPs without an adjuvant induced systemic as well as mucosal IgA antibody response. These results indicate that mucosal delivery of NoV VLPs is needed for induction of mucosal responses.

scholarly journals Rotavirus VP6 Adjuvant Effect on Norovirus GII.4 Virus-Like Particle Uptake and Presentation by Bone Marrow-Derived Dendritic Cells In Vitro and In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Kirsi Tamminen ◽  
Suvi Heinimäki ◽  
Timo Vesikari ◽  
Vesna Blazevic
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Adjuvant Effect ◽  
Particle Uptake ◽  
Virus Like Particle ◽  
Norovirus Gii ◽  
Immortalized Cell ◽  
Antigen Presenting

We have previously shown that rotavirus (RV) inner capsid protein VP6 has an adjuvant effect on norovirus (NoV) virus-like particle- (VLP-) induced immune responses and studied the adjuvant mechanism in immortalized cell lines used as antigen-presenting cells (APCs). Here, we investigated the uptake and presentation of RV VP6 and NoV GII.4 VLPs by primary bone marrow-derived dendritic cells (BMDCs). The adjuvant effect of VP6 on GII.4 VLP presentation and NoV-specific immune response induction by BMDC in vivo was also studied. Intracellular staining demonstrated that BMDCs internalized both antigens, but VP6 more efficiently than NoV VLPs. Both antigens were processed and presented to antigen-primed T cells, which responded by robust interferon γ secretion. When GII.4 VLPs and VP6 were mixed in the same pulsing reaction, a subpopulation of the cells had uptaken both antigens. Furthermore, VP6 copulsing increased GII.4 VLP uptake by 37% and activated BMDCs to secrete 2-5-fold increased levels of interleukin 6 and tumor necrosis factor α compared to VLP pulsing alone. When in vitro-pulsed BMDCs were transferred to syngeneic BALB/c mice, VP6 improved NoV-specific antibody responses. The results of this study support the earlier findings of VP6 adjuvant effect in vitro and in vivo.

scholarly journals Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice

2021 ◽  
Vol 118 (38) ◽  
pp. e2106845118
Author(s):  
Neil C. Dalvie ◽  
Sergio A. Rodriguez-Aponte ◽  
Brittany L. Hartwell ◽  
Lisa H. Tostanoski ◽  
Andrew M. Biedermann ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Viral Entry ◽  
Binding Domain ◽  
High Yield ◽  
Manufacturing Cost ◽  
Sequence Variant ◽  
Receptor Binding Domain ◽  
Middle Income ◽  
Middle Income Countries ◽  
Virus Like Particle

Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs). Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access. Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing cost. These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples. Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2. Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge.

scholarly journals Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding

2009 ◽  
Vol 106 (31) ◽  
pp. 12992-12997 ◽  
Author(s):  
T. S. Y. Guu ◽  
Z. Liu ◽  
Q. Ye ◽  
D. A. Mata ◽  
K. Li ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Hepatitis E Virus ◽  
Virus Assembly ◽  
Hepatitis E ◽  
Virus Like Particle

scholarly journals Immunological Cross-Reactivity of an Ancestral and the Most Recent Pandemic Norovirus GII.4 Variant

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 91 ◽  
Author(s):  
Kirsi Tamminen ◽  
Maria Malm ◽  
Timo Vesikari ◽  
Vesna Blazevic
Keyword(s):  
Antigenic Variation ◽  
Neutralization Assay ◽  
Cross Reactivity ◽  
High Avidity ◽  
Virus Like Particle ◽  
Blocking Activity ◽  
Ifn Γ ◽  
Pandemic Strains ◽  
Norovirus Gii ◽  
Antigen Presenting

Norovirus (NoV) genotype GII.4 is responsible for the majority of NoV infections causing pandemics every few years. A NoV virus-like particle (VLP)-based vaccine should optimally cover the high antigenic variation within the GII.4 genotype. We compared the immune responses generated by VLPs of the ancestral GII.4 1999 strain (GII.4 1995/96 US variant) and the most recent GII.4 Sydney 2012 pandemic strains in mice. No significant differences were observed in the type-specific responses but GII.4 1999 VLPs were more potent in inducing high-avidity antibodies with better cross-reactivity. GII.4 1999 immune sera blocked binding of GII.4 2006 and GII.4 2012 VLPs to the putative receptors in a surrogate neutralization assay, whereas GII.4 2012 immune sera only had low blocking activity against GII.4 2006 VLPs. Amino acid substitution in the NERK motif (amino acids 310, 316, 484, and 493, respectively), altering the access to conserved blocking epitope F, moderately improved the cross-blocking responses against mutated GII.4 2012 VLPs (D310N). NoV GII.4 1999 VLPs, uptaken and processed by antigen-presenting cells, induced stronger interferon gamma (IFN-γ) production from mice splenocytes than GII.4 2012 VLPs. These results support the use of GII.4 1999 VLPs as a major component of a NoV vaccine.

scholarly journals Immunogenicity and protective potency of Norovirus GII.17 virus-like particle-based vaccine

2020 ◽  
Vol 42 (7) ◽  
pp. 1211-1218
Author(s):  
Wei Chen ◽  
Tao Kang ◽  
Rongliang Yuan ◽  
Congwen Shao ◽  
Shenrong Jing
Keyword(s):  
Virus Like Particle ◽  
Norovirus Gii

scholarly journals Norovirus GII.4 antibodies in the Portuguese population

2014 ◽  
Vol 8 (09) ◽  
pp. 1201-1204 ◽  
Author(s):  
João Rodrigo Mesquita ◽  
Maria São José Nascimento
Keyword(s):  
Acute Gastroenteritis ◽  
Age Groups ◽  
Serum Samples ◽  
Portuguese Population ◽  
Seropositivity Rate ◽  
Virus Like Particle ◽  
Norovirus Gii ◽  
Sporadic Acute Gastroenteritis ◽  
Immune Assay

Introduction: Norovirus GII.4 is the leading cause of outbreaks of acute and sporadic acute gastroenteritis worldwide. Information on the prevalence of norovirus in Portugal is scarce or null. Methodology: We used a GII.4 norovirus virus-like particle-based enzyme immune assay to measure the seropositivity rate of GII.4 norovirus. Results: A total of 342 (70%) out of 473 serum samples tested positive for anti-GII.4 norovirus IgG. No statistically significant differences were found between regions, sex and age groups. Conclusion: Norovirus GII.4 infections are frequent in Portugal.

scholarly journals Identification of Human Norovirus GII.3 Blockade Antibody Epitopes

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2058
Author(s):  
Yufang Yi ◽  
Shuxia Wang ◽  
Xiaoli Wang ◽  
Pei Xiong ◽  
Qingwei Liu ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Acute Gastroenteritis ◽  
Pediatric Population ◽  
Blood Group Antigens ◽  
Human Norovirus ◽  
Chimeric Vlps ◽  
Virus Like Particle ◽  
Norovirus Gii ◽  
Vp1 Capsid Protein ◽  
Antibody Epitopes

Human noroviruses are a common pathogen causing acute gastroenteritis worldwide. Among all norovirus genotypes, GII.3 is particularly prevalent in the pediatric population. Here we report the identification of two distinct blockade antibody epitopes on the GII.3 capsid. We generated a panel of monoclonal antibodies (mAbs) from mice immunized with virus-like particle (VLP) of a GII.3 cluster 3 strain. Two of these mAbs, namely 8C7 and 8D1, specifically bound the parental GII.3 VLP but not VLPs of GII.4, GII.17, or GI.1. In addition, 8C7 and 8D1 efficiently blocked GII.3 VLP binding with its ligand, histo-blood group antigens (HBGA). These data demonstrate that 8C7 and 8D1 are GII.3-specific blockade antibodies. By using a series of chimeric VLPs, we mapped the epitopes of 8C7 and 8D1 to residues 385–400 and 401–420 of the VP1 capsid protein, respectively. These two blockade antibody epitopes are highly conserved among GII.3 cluster 3 strains. Structural modeling shows that the 8C7 epitope partially overlaps with the HBGA binding site (HBS) while the 8D1 epitope is spatially adjacent to HBS. These findings may enhance our understanding of the immunology and evolution of GII.3 noroviruses.

scholarly journals Engineered SARS-CoV-2 receptor binding domain improves immunogenicity in mice and elicits protective immunity in hamsters

2021 ◽  
Author(s):  
Neil C. Dalvie ◽  
Sergio A. Rodriguez-Aponte ◽  
Brittany L. Hartwell ◽  
Lisa H. Tostanoski ◽  
Andrew M. Biedermann ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Viral Entry ◽  
Binding Domain ◽  
High Yield ◽  
Sequence Variant ◽  
Receptor Binding Domain ◽  
Middle Income ◽  
Middle Income Countries ◽  
Virus Like Particle ◽  
Global Access

Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs).1 Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access.2 Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing costs.3 These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples.4–6 Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2.7,8 Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge.

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