Development of a novel monoclonal antibody with reactivity to a wide range of Venezuelan equine encephalitis virus strains

O’Brien, Lyn M.; Underwood-Fowler, Cindy; Goodchild, Sarah A.; Phelps, Amanda; Phillpotts, R. J.

doi:10.1186/1743-422x-6-206

Cited by 13 publications

(17 citation statements)

References 22 publications

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“…Furthermore, our results clearly indicate that the window in which antibody therapy of VEE is efficacious is short [36], [37], [61], [62], [68]. However, treatment offered a significant benefit for mice as demonstrated in this study.…”

Section: Discussionsupporting

confidence: 63%

Isolation and Characterisation of a Human-Like Antibody Fragment (scFv) That Inactivates VEEV In Vitro and In Vivo

et al. 2012

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Venezuelan equine encephalitis virus (VEEV) belongs to the Alphavirus genus and several species of this family are pathogenic to humans. The viruses are classified as potential agents of biological warfare and terrorism and sensitive detection as well as effective prophylaxis and antiviral therapies are required.In this work, we describe the isolation of the anti-VEEV single chain Fragment variable (scFv), ToR67-3B4, from a non-human primate (NHP) antibody gene library. We report its recloning into the bivalent scFv-Fc format and further immunological and biochemical characterisation.The scFv-Fc ToR67-3B4 recognised viable as well as formalin and ß-propionolactone (ß-Pl) inactivated virus particles and could be applied for immunoblot analysis of VEEV proteins and immuno-histochemistry of VEEV infected cells. It detected specifically the viral E1 envelope protein of VEEV but did not react with reduced viral glycoprotein preparations suggesting that recognition depends upon conformational epitopes. The recombinant antibody was able to detect multiple VEEV subtypes and displayed only marginal cross-reactivity to other Alphavirus species except for EEEV. In addition, the scFv-Fc fusion described here might be of therapeutic use since it successfully inactivated VEEV in a murine disease model. When the recombinant antibody was administered 6 hours post challenge, 80% to 100% of mice survived lethal VEEV IA/B or IE infection. Forty to sixty percent of mice survived when scFv-Fc ToR67-3B4 was applied 6 hours post challenge with VEEV subtypes II and former IIIA. In combination with E2-neutralising antibodies the NHP antibody isolated here could significantly improve passive protection as well as generic therapy of VEE.

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Section: Discussionsupporting

confidence: 63%

Isolation and Characterisation of a Human-Like Antibody Fragment (scFv) That Inactivates VEEV In Vitro and In Vivo

et al. 2012

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“…According to other data, the mechanism of protection did not appear to depend upon neutralization [131]. Similar results were obtained by O'Brien et al, which described a non-neutralizing mAb (IgG2a), named CUF37-2a, able to protect 50% of mice from a subcutaneous VEEV challenge when a dose of 9.15 μ g of mAb was administered 24 h prior to challenge [132]. …”

Section: Alphavirusessupporting

confidence: 75%

Possible Future Monoclonal Antibody (mAb)-Based Therapy against Arbovirus Infections

Mancini

Gorini

Clementi

et al. 2013

BioMed Research International

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More than 150 arboviruses belonging to different families are known to infect humans, causing endemic infections as well as epidemic outbreaks. Effective vaccines to limit the occurrence of some of these infections have been licensed, while for the others several new immunogens are under development mostly for their improvements concerning safety and effectiveness profiles. On the other hand, specific and effective antiviral drugs are not yet available, posing an urgent medical need in particular for emergency cases. Neutralizing monoclonal antibodies (mAbs) have been demonstrated to be effective in the treatment of several infectious diseases as well as in preliminary in vitro and in vivo models of arbovirus-related infections. Given their specific antiviral activity as well-tolerated molecules with limited side effects, mAbs could represent a new therapeutic approach for the development of an effective treatment, as well as useful tools in the study of the host-virus interplay and in the development of more effective immunogens. However, before their use as candidate therapeutics, possible hurdles (e.g., Ab-dependent enhancement of infection, occurrence of viral escape variants) must be carefully evaluated. In this review are described the main arboviruses infecting humans and candidate mAbs to be possibly used in a future passive immunotherapy.

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“…For passive immunization, human 55 and murine 56 antibody candidates for further therapeutic development have been described for Chikungunya. A panel of neutralizing murine, 26 , 57 humanized, 58 - 61 human-like monoclonal antibodies from non-human primates 46 and one human antibody 44 have been described for VEEV.…”

Section: Discussionmentioning

confidence: 99%

Human-like antibodies neutralizing Western equine encephalitis virus

Hülseweh

Rülker

Pelat

et al. 2014

mAbs

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This study describes the development of the first neutralizing antibodies against Western equine encephalitis virus (WEEV), a member of the genus Alphavirus. WEEV is transmitted by mosquitoes and can spread to the human central nervous system, causing symptoms ranging from mild febrile reactions to life-threatening encephalitis. WEEV has been classified as a biological warfare agent by the US Centers for Disease Control and Prevention. No anti-WEEV drugs are currently commercially available. Neutralizing antibodies are useful for the pre- and post-exposure treatment of WEEV infections. In this study, two immune antibody gene libraries were constructed from two macaques immunized with inactivated WEEV. Four antibodies were selected from these libraries and recloned as scFv-Fc, with a human Fc part. These antibodies bound WEEV specifically in ELISA with little or no cross-reaction with other alphaviruses. They were further analyzed by immunohistochemistry. All binders were suitable for the intracellular detection of WEEV particles. Neutralizing activity was determined in vitro. Three of the four antibodies were found to be neutralizing; about 1 ng/mL of the best antibody (ToR69–3A2) neutralized 50% of 5x104 TCID50/mL. Due to its human-like nature with a germinality index of 89% (VH) and 91% (VL), the ToR69–3A2 antibody is a promising candidate for future passive vaccine development.

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Development of a novel monoclonal antibody with reactivity to a wide range of Venezuelan equine encephalitis virus strains

Cited by 13 publications

References 22 publications

Isolation and Characterisation of a Human-Like Antibody Fragment (scFv) That Inactivates VEEV In Vitro and In Vivo

Isolation and Characterisation of a Human-Like Antibody Fragment (scFv) That Inactivates VEEV In Vitro and In Vivo

Possible Future Monoclonal Antibody (mAb)-Based Therapy against Arbovirus Infections

Human-like antibodies neutralizing Western equine encephalitis virus

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