scholarly journals Broadly cross-reactive human antibodies that inhibit genogroup I and II noroviruses

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gabriela Alvarado ◽  
Wilhelm Salmen ◽  
Khalil Ettayebi ◽  
Liya Hu ◽  
Banumathi Sankaran ◽  
...  
Keyword(s):  
Deep Understanding ◽  
Neutralization Assay ◽  
Blood Group Antigen ◽  
Vaccine Candidates ◽  
Human Antibodies ◽  
Virus Neutralization Assay ◽  
Rational Development ◽  
Naturally Occurring ◽  
P Domain ◽  
Blocking Assay

AbstractThe rational development of norovirus vaccine candidates requires a deep understanding of the antigenic diversity and mechanisms of neutralization of the virus. Here, we isolate and characterize a panel of broadly cross-reactive naturally occurring human monoclonal IgMs, IgAs and IgGs reactive with human norovirus (HuNoV) genogroup I or II (GI or GII). We note three binding patterns and identify monoclonal antibodies (mAbs) that neutralize at least one GI or GII HuNoV strain when using a histo-blood group antigen (HBGA) blocking assay. The HBGA blocking assay and a virus neutralization assay using human intestinal enteroids reveal that the GII-specific mAb NORO-320, mediates HBGA blocking and neutralization of multiple GII genotypes. The Fab form of NORO-320 neutralizes GII.4 infection more potently than the mAb, however, does not block HBGA binding. The crystal structure of NORO-320 Fab in complex with GII.4 P-domain shows that the antibody recognizes a highly conserved region in the P-domain distant from the HBGA binding site. Dynamic light scattering analysis of GII.4 virus-like particles with mAb NORO-320 shows severe aggregation, suggesting neutralization is by steric hindrance caused by multivalent cross-linking. Aggregation was not observed with the Fab form of NORO-320, suggesting that this clone also has additional inhibitory features.

Naturally Occurring Human Antibodies with Specificity for Light Chains of Immunoglobulins

Vox Sanguinis ◽  
1977 ◽  
Vol 32 (2) ◽  
pp. 69-76
Author(s):  
Rudolf Scherz ◽  
Rolf Pflugshaupt ◽  
René Bütler
Keyword(s):  
Light Chains ◽  
Human Antibodies ◽  
Naturally Occurring

scholarly journals Systemic and local antibodies induced by an experimental inactivated vaccine against bovine herpesvirus type 1

2011 ◽  
Vol 41 (2) ◽  
pp. 307-313
Author(s):  
Maria do Carmo Cilento ◽  
Edviges Maristela Pituco ◽  
Ricardo Spacagna Jordão ◽  
Cláudia Pestana Ribeiro ◽  
Moacir Marchiori Filho ◽  
...  
Keyword(s):  
Bovine Herpesvirus ◽  
Neutralization Assay ◽  
Elisa Test ◽  
Antibody Responses ◽  
Inactivated Vaccine ◽  
Serum Samples ◽  
Post Vaccination ◽  
Herpesvirus Type ◽  
Virus Neutralization Assay ◽  
Igg2 Antibody

An experimental inactivated vaccine against bovine herpesvirus-1 (BoHV-1) was produced aiming to evaluate the systemic and local antibody responses in 12 seronegative heifers, after vaccination and revaccination. Serum samples were submitted to virus neutralization assay and to ELISA test for detection of IgG1 and IgG2 isotypes. Nasal secretion samples were submitted to the same ELISA test for detection of IgG1 and IgG2 isotypes. The results showed that moderate to high neutralizing titres and IgG1 and IgG2 antibody responses were induced after the second vaccination in the serum and in nasal secretions up to 114 days post vaccination. IgG2 antibodies were the prevalent isotype for most of the post-vaccination period. The results indicate that BoHV-1 experimental inactivated vaccine elicited potentially protective IgG1 and IgG2 antibody levels, both in the systemic and mucosal compartments.

scholarly journals The P Domain of Norovirus Capsid Protein Forms a Subviral Particle That Binds to Histo-Blood Group Antigen Receptors

2005 ◽  
Vol 79 (22) ◽  
pp. 14017-14030 ◽  
Author(s):  
Ming Tan ◽  
Xi Jiang
Keyword(s):  
Blood Group ◽  
Receptor Binding ◽  
Vaccine Development ◽  
Human Colon ◽  
Blood Group Antigen ◽  
Antigen Receptors ◽  
Human Colon Carcinoma Cell ◽  
Strong Binding ◽  
Internal Core ◽  
P Domain

ABSTRACT Norovirus is the most important cause of nonbacterial acute gastroenteritis. We have shown previously that the isolated P domain containing the hinge forms a dimer and binds to histo-blood group antigen (HBGA) receptors with a low affinity (M. Tan, R. S. Hegde, and X. Jiang, J. Virol. 78:6233-6242, 2004). Here, we reported that the P domain of VA387 without the hinge forms a small particle with a significantly increased receptor binding affinity. An end-linked oligopeptide containing one or more cysteines promoted P-particle formation by forming intermolecular disulfide bridges. The binding sensitivity of the P particle to HBGAs was enhanced >700-fold compared to the P dimer, which was comparable to that of virus-like particles. The binding specificity of the P particle was further confirmed by strong binding to the Caco-2 cells, a human colon carcinoma cell line. This binding enhancement was observed in the P particles of both norovirus GI and GII strains. The P particle is estimated to contain 12 P dimers, in which the P2 subdomain builds up the outer layer, while the P1 subdomain forms the internal core. Taken together, our data indicate that the P domain is involved not only in dimerization but also in polymerization of the protein during the capsid assembling. The enhanced receptor binding of the P particle reflects the intrinsic feature of the viral capsid. The easy production of the P particle and its strong binding to HBGAs suggest that the P particle is useful in studying pathogenesis and morphogenesis of norovirus and candidates for antiviral or vaccine development.

scholarly journals Neutralization Assay for Zika and Dengue Viruses by Use of Real-Time-PCR-Based Endpoint Assessment

2017 ◽  
Vol 55 (10) ◽  
pp. 3104-3112 ◽  
Author(s):  
Heather L. Wilson ◽  
Thomas Tran ◽  
Julian Druce ◽  
Myrielle Dupont-Rouzeyrol ◽  
Michael Catton
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
High Sensitivity ◽  
Neutralization Assay ◽  
Cross Reactivity ◽  
Health Concern ◽  
Confirmatory Test ◽  
Virus Neutralization Assay ◽  
History Of ◽  
Infective Complications

ABSTRACTThe global spread and infective complications of Zika virus (ZKV) and dengue virus (DENV) have made them flaviviruses of public health concern. Serological diagnosis can be challenging due to antibody cross-reactivity, particularly in secondary flavivirus infections or when there is a history of flavivirus vaccination. The virus neutralization assay is considered to be the most specific assay for measurement of anti-flavivirus antibodies. This study describes an assay where the neutralization endpoint is measured by real-time PCR, providing results within 72 h. It demonstrated 100% sensitivity (24/24 ZKV and 15/15 DENV) and 100% specificity (11/11 specimens) when testing well-characterized sera. In addition, the assay was able to determine the correct DENV serotype in 91.7% of cases. The high sensitivity and specificity of the real-time PCR neutralization assay makes it suitable to use as a confirmatory test for sera that are reactive in commercial IgM/IgG enzyme immunoassays. Results are objective and the PCR-based measurement of the neutralization endpoint lends itself to automation so that throughput may be increased in times of high demand.

scholarly journals Serum Opacity Factor (SOF) of Streptococcus pyogenes Evokes Antibodies That Opsonize Homologous and Heterologous SOF-Positive Serotypes of Group A Streptococci

2003 ◽  
Vol 71 (9) ◽  
pp. 5097-5103 ◽  
Author(s):  
Harry S. Courtney ◽  
David L. Hasty ◽  
James B. Dale
Keyword(s):  
Streptococcus Pyogenes ◽  
Rabbit Antiserum ◽  
M Protein ◽  
Group A Streptococci ◽  
Streptococcal Infections ◽  
Vaccine Candidates ◽  
Human Antibodies ◽  
Serum Opacity Factor ◽  
Group A

ABSTRACT Serum opacity factor (SOF) is a protein expressed by Streptococcus pyogenes that opacifies mammalian serum. SOF is also a virulence factor of S. pyogenes, but it has not been previously shown to elicit a protective immune response. Herein, we report that SOF evokes bactericidal antibodies against S. pyogenes in humans, rabbits, and mice. Rabbit antiserum against purified recombinant SOF2 opsonized SOF-positive M type 2, 4, and 28 S. pyogenes in human blood but had no effect on SOF-negative M type 5 S. pyogenes. Furthermore, affinity-purified human antibodies against SOF2 also opsonized SOF-positive streptococci. A combination of antisera against M2 and SOF2 proteins was dramatically more effective in killing streptococci than either antiserum alone, indicating that antibodies against SOF2 enhance the opsonic efficiency of M protein antibodies. Mice tolerated an intravenous injection of 100 μg of SOF without overt signs of toxicity, and immunization with SOF protected mice against challenge infections with M type 2 S. pyogenes. These data indicate that SOF evokes opsonic antibodies that may protect against infections by SOF-positive serotypes of group A streptococci and suggest that different serotypes of SOF have common epitopes that may be useful vaccine candidates to protect against group A streptococcal infections.

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