scholarly journals Isolation of Monoclonal Antibodies from Zika Virus-Infected Patient Samples

2020 ◽  
pp. 261-288
Author(s):  
Qihui Wang ◽  
Jinghua Yan
Keyword(s):  
Monoclonal Antibodies ◽  
Zika Virus ◽  
Infected Patient

scholarly journals Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques

2017 ◽  
Vol 9 (410) ◽  
pp. eaan8184 ◽  
Author(s):  
Diogo M. Magnani ◽  
Thomas F. Rogers ◽  
Nathan Beutler ◽  
Michael J. Ricciardi ◽  
Varian K. Bailey ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Virus Infection ◽  
Pregnant Women ◽  
Receptor Binding ◽  
Zika Virus ◽  
Infected Patient ◽  
Nonhuman Primates ◽  
Fcγ Receptor ◽  
Human Monoclonal Antibodies ◽  
Zikv Infection

Therapies to prevent maternal Zika virus (ZIKV) infection and its subsequent fetal developmental complications are urgently required. We isolated three potent ZIKV-neutralizing monoclonal antibodies (nmAbs) from the plasmablasts of a ZIKV-infected patient—SMZAb1, SMZAb2, and SMZAb5—directed against two different domains of the virus. We engineered these nmAbs with Fc LALA mutations that abrogate Fcγ receptor binding, thus eliminating potential therapy-mediated antibody-dependent enhancement. We administered a cocktail of these three nmAbs to nonhuman primates 1 day before challenge with ZIKV and demonstrated that the nmAbs completely prevented viremia in serum after challenge. Given that numerous antibodies have exceptional safety profiles in humans, the cocktail described here could be rapidly developed to protect uninfected pregnant women and their fetuses.

scholarly journals Dengue and Zika Virus Cross-Reactive Human Monoclonal Antibodies Protect against Spondweni Virus Infection and Pathogenesis in Mice

Cell Reports ◽  
2019 ◽  
Vol 26 (6) ◽  
pp. 1585-1597.e4 ◽  
Author(s):  
Vanessa Salazar ◽  
Brett W. Jagger ◽  
Juthathip Mongkolsapaya ◽  
Katherine E. Burgomaster ◽  
Wanwisa Dejnirattisai ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Virus Infection ◽  
Zika Virus ◽  
Human Monoclonal Antibodies

scholarly journals Complete Genome Sequence of a Zika Virus Strain Isolated from the Serum of an Infected Patient in Thailand in 2006

2018 ◽  
Vol 6 (10) ◽  
Author(s):  
Narong Nitatpattana ◽  
Kumchol Chaiyo ◽  
Supoth Rajakam ◽  
Kanya Poolam ◽  
Kusuma Chansiprasert ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Genome Sequence ◽  
Virus Strain ◽  
Zika Virus ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Infected Patient ◽  
Vero Cells ◽  
Asian Lineage

ABSTRACT The complete genome of Zika virus (ZIKV) strain CVD_06-274 was isolated from the serum of an infected patient in Thailand in 2006. Phylogenetic analysis showed that this strain belongs to the Asian lineage and also high titers in Vero cells (RCB 10-87). It has potential for development as an inactivated ZIKV vaccine.

scholarly journals Dengue Virus Envelope Dimer Epitope Monoclonal Antibodies Isolated from Dengue Patients Are Protective against Zika Virus

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
J. A. Swanstrom ◽  
J. A. Plante ◽  
K. S. Plante ◽  
E. F. Young ◽  
E. McGowan ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Dengue Virus ◽  
Pregnant Women ◽  
Zika Virus ◽  
Neutralizing Antibodies ◽  
Severe Disease ◽  
Fetal Loss ◽  
Human Monoclonal Antibodies ◽  
Serum Dilution ◽  
Homologous Virus

ABSTRACT Zika virus (ZIKV) is a mosquito-borne flavivirus responsible for thousands of cases of severe fetal malformations and neurological disease since its introduction to Brazil in 2013. Antibodies to flaviviruses can be protective, resulting in lifelong immunity to reinfection by homologous virus. However, cross-reactive antibodies can complicate flavivirus diagnostics and promote more severe disease, as noted after serial dengue virus (DENV) infections. The endemic circulation of DENV in South America and elsewhere raises concerns that preexisting flavivirus immunity may modulate ZIKV disease and transmission potential. Here, we report on the ability of human monoclonal antibodies and immune sera derived from dengue patients to neutralize contemporary epidemic ZIKV strains. We demonstrate that a class of human monoclonal antibodies isolated from DENV patients neutralizes ZIKV in cell culture and is protective in a lethal murine model. We also tested a large panel of convalescent-phase immune sera from humans exposed to primary and repeat DENV infection. Although ZIKV is most closely related to DENV compared to other human-pathogenic flaviviruses, most DENV immune sera (73%) failed to neutralize ZIKV, while others had low (50% effective concentration [EC 50 ], <1:100 serum dilution; 18%) or moderate to high (EC 50 , >1:100 serum dilution; 9%) levels of cross-neutralizing antibodies. Our results establish that ZIKV and DENV share epitopes that are targeted by neutralizing, protective human antibodies. The availability of potently neutralizing human monoclonal antibodies provides an immunotherapeutic approach to control life-threatening ZIKV infection and also points to the possibility of repurposing DENV vaccines to induce cross-protective immunity to ZIKV. IMPORTANCE ZIKV is an emerging arbovirus that has been associated with severe neurological birth defects and fetal loss in pregnant women and Guillain-Barré syndrome in adults. Currently, there is no vaccine or therapeutic for ZIKV. The identification of a class of antibodies (envelope dimer epitope 1 [EDE1]) that potently neutralizes ZIKV in addition to all four DENV serotypes points to a potential immunotherapeutic to combat ZIKV. This is especially salient given the precedent of antibody therapy to treat pregnant women infected with other viruses associated with microcephaly, such as cytomegalovirus and rubella virus. Furthermore, the identification of a functionally conserved epitope between ZIKV and DENV raises the possibility that a vaccine may be able to elicit neutralizing antibodies against both viruses.

scholarly journals Human Monoclonal Antibodies Potently Neutralize Zika Virus and Select for Escape Mutations on the Lateral Ridge of the Envelope Protein

2019 ◽  
Vol 93 (14) ◽  
Author(s):  
Mark J. Bailey ◽  
Felix Broecker ◽  
Alec W. Freyn ◽  
Angela Choi ◽  
Julia A. Brown ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Amino Acid ◽  
Virus Infection ◽  
Zika Virus ◽  
Envelope Protein ◽  
Severe Disease ◽  
Guillain Barre Syndrome ◽  
Antibody Dependent Enhancement ◽  
Lateral Ridge ◽  
Guillain Barré

ABSTRACT The mosquito-borne Zika virus (ZIKV) has been causing epidemic outbreaks on a global scale. Virus infection can result in severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Here, we characterized monoclonal antibodies isolated from a patient with an active Zika virus infection that potently neutralized virus infection in Vero cells at the nanogram-per-milliliter range. In addition, these antibodies enhanced internalization of virions into human leukemia K562 cells in vitro, indicating their possible ability to cause antibody-dependent enhancement of disease. Escape variants of the ZIKV MR766 strain to a potently neutralizing antibody, AC10, exhibited an amino acid substitution at residue S368 in the lateral ridge region of the envelope protein. Analysis of publicly availably ZIKV sequences revealed the S368 site to be conserved among the vast majority (97.6%) of circulating strains. We validated the importance of this residue by engineering a recombinant virus with an S368R point mutation that was unable to be fully neutralized by AC10. Four out of the 12 monoclonal antibodies tested were also unable to neutralize the virus with the S368R mutation, suggesting this region to be an important immunogenic epitope during human infection. Last, a time-of-addition infection assay further validated the escape variant and showed that all monoclonal antibodies inhibited virus binding to the cell surface. Thus, the present study demonstrates that the lateral ridge region of the envelope protein is likely an immunodominant, neutralizing epitope. IMPORTANCE Zika virus (ZIKV) is a global health threat causing severe disease in humans, including microcephaly in newborns and Guillain-Barré syndrome in adults. Here, we analyzed the human monoclonal antibody response to acute ZIKV infection and found that neutralizing antibodies could not elicit Fc-mediated immune effector functions but could potentiate antibody-dependent enhancement of disease. We further identified critical epitopes involved with neutralization by generating and characterizing escape variants by whole-genome sequencing. We demonstrate that the lateral ridge region, particularly the S368 amino acid site, is critical for neutralization by domain III-specific antibodies.

scholarly journals Both structure and function of human monoclonal antibodies contribute to enhancement of Zika virus infectivity in vitro

2017 ◽  
Vol 60 (12) ◽  
pp. 1396-1398 ◽  
Author(s):  
Min Li ◽  
Xin Wang ◽  
Qihui Wang ◽  
Lei Yu ◽  
Lanfeng Wang ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Zika Virus ◽  
Structure And Function ◽  
Virus Infectivity ◽  
Human Monoclonal Antibodies ◽  
And Function

scholarly journals Neutralizing and non-neutralizing monoclonal antibodies against dengue virus E protein derived from a naturally infected patient

2010 ◽  
Vol 7 (1) ◽  
Author(s):  
John S Schieffelin ◽  
Joshua M Costin ◽  
Cindo O Nicholson ◽  
Nicole M Orgeron ◽  
Krystal A Fontaine ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Dengue Virus ◽  
Infected Patient ◽  
E Protein
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