Generation and characterization of neutralizing human recombinant antibodies against antigenic site II of rabies virus glycoprotein

Sun, Li; Chen, Zhe; Yu, Li; Wei, Jingshuang; Li, Chuan; Jin, Jing; Shen, Xinxin; Lv, Xiaoyang; Tang, Qing; Li, Dexin; Liang, Mifang

doi:10.1007/s00253-012-4171-4

Cited by 18 publications

(4 citation statements)

References 33 publications

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“…Indeed, REGN-EB3, a three-mAb cocktail against EBOV G was recently approved by the FDA as a treatment for EBOV infection [41]. Similar to EBOV, several mAb cocktails have been developed for use against RABV infections [28,[42][43][44][45][46][47]. In phase 2/3 clinical trials, PEP regimens containing anti-rabies mAb cocktail TwinrabTM (docaravimab and miromavimab) [48] or mAb SII RMAb (Rabishield) [49] demonstrated noninferiority to HRIG in the window of protection and rabies virus neutralizing activity respectively.…”

Section: Discussionmentioning

confidence: 99%

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

Weir

Coggins

et al. 2021

Viruses

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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.

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Section: Discussionmentioning

confidence: 99%

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

Weir

Coggins

et al. 2021

Viruses

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“…Indeed, REGN-EB3, a three-mAb cocktail against EBOV-G was recently approved by the FDA as a treatment for EBOV infection [41]. Similar to EBOV, several mAb cocktails have been developed for use against RABV infections [42][43][44][45][46]. However, since mAb cocktail therapy is still a developing field, it is important to consider potential escape mutants that result from cocktail treatments [47,48].…”

Section: Discussionmentioning

confidence: 99%

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

Weir¹,

Coggins²,

Vu³

et al. 2021

Preprint

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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.

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“…Some antigenic sites on RABV G protein recognized by mAbs were relatively close in spatial structure, such as antigenic sites II and III, and this spatial conformation would lead to mutual binding inhibition between mAbs. 27 Comparatively, antigenic sites I and III were well separated in space. 2 Based on the above considerations, we selected antigenic sites I and III as the targets to develop a bispecific antibody.…”

Section: Introductionmentioning

confidence: 97%

“…According to previous studies, the majority of neutralizing antibodies induced by human rabies vaccines targeted antigenic sites I and III of RABV G protein, 26 and it seemed reasonable to assume that antigenic sites I and III played a more dominant role in viral infection. Some antigenic sites on RABV G protein recognized by mAbs were relatively close in spatial structure, such as antigenic sites II and III, and this spatial conformation would lead to mutual binding inhibition between mAbs 27 . Comparatively, antigenic sites I and III were well separated in space 2 .…”

Section: Introductionmentioning

confidence: 98%

Development of a novel bispecific antibody GR1801 for rabies

Long,

Wang,

Hao

et al. 2023

Journal of Medical Virology

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Rabies is a zoonotic viral disease characterized by an almost 100% fatality rate once symptoms appear. However, it can be prevented through timely postexposure prophylaxis (PEP). Currently, there is a growing trend to replace polyclonal rabies immune globulin (RIG) with monoclonal antibodies (mAbs) in rabies PEP. In this study, we developed a human bispecific antibody, GR1801, by combining two mAbs, A2 and B353, which target distinct epitopes. GR1801 is an asymmetric immunoglobulin G1 molecule, with one arm (A2 targeting epitope III) in fragment antigen‐binding (Fab) form and the other arm (B353 targeting epitope I) in single‐chain variable fragment (scFv) form, constructed using Knobs‐into‐Holes technology. GR1801 demonstrated the ability to neutralize 90 naturally occurring rabies virus (RABV) glycoprotein antigenic variants, 21 pseudotyped, and 18 live street RABVs, exhibiting broad‐spectrum neutralizing activity. In vivo, GR1801 provided protection equivalent to that of human RIG in golden hamsters challenged with lethal RABV. In conclusion, these findings demonstrate the neutralization potency and breadth of GR1801, which can be a promising candidate drug for rabies PEP, and a comprehensive testing against a broad spectrum of Chinese prevalent RABVs will be investigated in great detail in the future for the in vitro and in vivo studies.

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Generation and characterization of neutralizing human recombinant antibodies against antigenic site II of rabies virus glycoprotein

Cited by 18 publications

References 33 publications

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

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

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

Development of a novel bispecific antibody GR1801 for rabies

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