scholarly journals Isolation and Characterization of Cross-Reactive Human Monoclonal Antibodies That Potently Neutralize Australian Bat Lyssavirus Variants and Other Phylogroup 1 Lyssaviruses

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 391
Author(s):  
Dawn L. Weir ◽  
Si’Ana A. Coggins ◽  
Bang K. Vu ◽  
Jessica Coertse ◽  
Lianying Yan ◽  
...  

Australian bat lyssavirus (ABLV) is a rhabdovirus that circulates in four species of pteropid bats (ABLVp) and the yellow-bellied sheath-tailed bat (ABLVs) in mainland Australia. In the three confirmed human cases of ABLV, rabies illness preceded fatality. As with rabies virus (RABV), post-exposure prophylaxis (PEP) for potential ABLV infections consists of wound cleansing, administration of the rabies vaccine and injection of rabies immunoglobulin (RIG) proximal to the wound. Despite the efficacy of PEP, the inaccessibility of human RIG (HRIG) in the developing world and the high immunogenicity of equine RIG (ERIG) has led to consideration of human monoclonal antibodies (hmAbs) as a passive immunization option that offers enhanced safety and specificity. Using a recombinant vesicular stomatitis virus (rVSV) expressing the glycoprotein (G) protein of ABLVs and phage display, we identified two hmAbs, A6 and F11, which completely neutralize ABLVs/ABLVp, and RABV at concentrations ranging from 0.39 and 6.25 µg/mL and 0.19 and 0.39 µg/mL respectively. A6 and F11 recognize overlapping epitopes in the lyssavirus G protein, effectively neutralizing phylogroup 1 lyssaviruses, while having little effect on phylogroup 2 and non-grouped diverse lyssaviruses. These results suggest that A6 and F11 could be effective therapeutic and diagnostic tools for phylogroup 1 lyssavirus infections.

Author(s):  
Dawn Weir ◽  
Si'Ana Coggins ◽  
Bang Vu ◽  
Jessica Coertse ◽  
Lianying Yan ◽  
...  

Australian bat lyssavirus (ABLV) is a rhabdovirus that circulates in four species of pteropid bats (ABLVp) and the yellow-bellied sheath-tailed bat (ABLVs) in mainland Australia. In the three confirmed human cases of ABLV, rabies illness preceded fatality. As with rabies virus (RABV), post-exposure prophylaxis (PEP) for potential ABLV infections consists of wound cleansing, ad-ministration of the rabies vaccine and injection of rabies immunoglobulin (RIG) proximal to the wound. Despite the efficacy of PEP, the inaccessibility of human RIG (HRIG) in the developing world and the high immunogenicity of equine RIG (ERIG) has led to consideration of human monoclonal antibodies (hmAbs) as a passive immunization option that offers enhanced safety and specificity. Using a recombinant vesicular stomatitis virus (rVSV) expressing the glycoprotein (G) protein of ABLVs and phage display, we identified two hmAbs, A6 and F11, which completely neutralize ABLVs/ABLVp, and RABV at concentrations ranging from 0.19-3.12 µg/mL and 0.39-6.25 µg/mL respectively. A6 and F11 recognize overlapping epitopes in the lyssavirus G protein, ef-fectively neutralizing phylogroup 1 lyssaviruses, while having little effect on phylogroup 2 and non-grouped diverse lyssaviruses. These results suggest A6 and F11 could be effective therapeutic and diagnostic tools for phylogroup 1 lyssavirus infections.


2016 ◽  
Vol 8 (4) ◽  
pp. 407-421 ◽  
Author(s):  
Paola De Benedictis ◽  
Andrea Minola ◽  
Elena Rota Nodari ◽  
Roberta Aiello ◽  
Barbara Zecchin ◽  
...  

Virology ◽  
2007 ◽  
Vol 358 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Flavia Ferrantelli ◽  
Kathleen A. Buckley ◽  
Robert A. Rasmussen ◽  
Alistair Chalmers ◽  
Tao Wang ◽  
...  

Vaccine ◽  
2001 ◽  
Vol 19 (28-29) ◽  
pp. 3834-3842 ◽  
Author(s):  
C.A Hanlon ◽  
C.A DeMattos ◽  
C.C DeMattos ◽  
M Niezgoda ◽  
D.C Hooper ◽  
...  

AIDS ◽  
2003 ◽  
Vol 17 (3) ◽  
pp. 301-309 ◽  
Author(s):  
Flavia Ferrantelli ◽  
Regina Hofmann-Lehmann ◽  
Robert A Rasmussen ◽  
Tao Wang ◽  
Weidong Xu ◽  
...  

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 139 ◽  
Author(s):  
Guillaume Goyette-Desjardins ◽  
Sonia Lacouture ◽  
Jean-Philippe Auger ◽  
René Roy ◽  
Marcelo Gottschalk ◽  
...  

Streptococcus suis serotype 2 is an encapsulated bacterium and an important swine pathogen. Opsonizing antibody responses targeting capsular polysaccharides (CPSs) are protective against extracellular pathogens. To elucidate the protective activity of monoclonal antibodies (mAbs) directed against S. suis serotype 2 CPS, mice were immunized with a serotype 2 CPS-glycoconjugate and three hybridomas were isolated; of which, two were murine IgMs and the other a murine IgG1. Whereas the IgMs (mAbs 9E7 and 13C8) showed different reactivity levels with S. suis serotypes 1, 1/2, 2 and 14, the IgG1 (mAb 16H11) was shown to be serotype 2-specific. All mAbs targeted the sialylated chain of the CPSs. Using an opsonophagocytosis assay, the IgMs were opsonizing towards the S. suis serotypes to which they cross-react, while the IgG1 failed to induce bacterial elimination. In a model of mouse passive immunization followed by a lethal challenge with S. suis serotype 2, the IgG1 and IgM cross-reacting only with serotype 14 (mAb 13C8) failed to protect, while the IgM cross-reacting with serotypes 1, 1/2, and 14 (mAb 9E7) was shown to be protective by limiting bacteremia. These new mAbs show promise as new S. suis diagnostic tools, as well as potential for therapeutic applications.


2021 ◽  
Author(s):  
Igor Stoma

Infectious disease (ID) are a major cause of morbidity and fatality in the ICH and moreover IDs may trigger underlying diseases or graft versus host disease (GVHD) and organ rejection. To reduce risk, management of ID in ICH requires a comprehensive management from day 1, with (1) reduction of exposures: fewer social contacts; cocooning (vaccination of any close contacts); appropriate “low pathogen-diet”; avoiding environmental exposures (dust); (2) Detection of pre-existing risks (latent infections, vaccination history); (3) bearing in mind “expected IDs” by type and severity of immunosuppression. Inactivated vaccines have similar reactogenicity and safety profiles in the ICH and health subjects; however due to reduced immunogenicity, efficacy may be reduced. Live vaccines are usually contraindicated as they may cause harm in severely immunocompromised patients; however, they can be considered based on an individual risk-benefit assessment with remaining immune functions in mind. In some instances, post-exposure prophylaxis with immunoglobulins is effective, (“passive immunization”) specifically against measles and the varicella-zoster-virus. For the latter, antivirals can be used as an alternative.


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