A recombinant humanized monoclonal antibody completely protects mice against lethal challenge with Venezuelan equine encephalitis virus

Hu, Weigang; Phelps, Amanda; Jager, Scott; Chau, Damon; Hu, Charles C.; O’Brien, Lyn M.; Perkins, Stephanie D.; Gates, Amanda; Phillpotts, R. J.; Nagata, Les P.

doi:10.1016/j.vaccine.2010.06.038

Cited by 25 publications

(29 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The optimal time for administration of the recombinant binder post challenge seems to be a matter of antibody half-life and clearance. For scFv-Fc ToR67-3B4 the half life was estimated to 1.68 days which is slightly lower than the half-lives of two previously investigated antibodies [68], [69].…”

Section: Discussionmentioning

confidence: 61%

See 1 more Smart Citation

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

et al. 2012

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 61%

“…Most of them are directed against the E2 protein, only a few targeted the viral E1 protein [61], [62], [69], [73], [78].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

Self Cite

View full text Add to dashboard Cite

show abstract

“…Further, a purified humanized neutralizing antibody against the VEEV E2 protein was able to provide complete protection in mice when administered 24 hours before or after challenge with VEEV. 52 A similar humanized Mab, hu1A3B-7, has been reported recently with broad serogroup specificity. 53 Hu1A3B-7 showed neutralizing activity in vitro and protected mice infected via aerosol and subcutaneous routes with the VEEV TrD strain.…”

Section: Immunotherapeuticsmentioning

confidence: 83%

State-of-the-Art Therapeutic Medical Countermeasures for Viral Threat Agents

Sampath¹,

Metz²,

Stundick³

et al. 2011

Biosecurity and Bioterrorism: Biodefense Strategy, Practice, an

View full text Add to dashboard Cite

In recent years, there has been an increase in the perceived threat of biological agents being used against civilian populations. This has prompted an urgent need for the development and procurement of medical countermeasures (MCMs) against highly pathogenic viruses that can prevent morbidity and mortality from infections caused by these agents. To date, antiviral drug development has been largely focused on clinically prevalent chronic infections due to their commercial viability. This has left a huge gap in the drug development path for acute infections of biodefense importance. In this review, we discuss the antiviral research and development initiatives focusing specifically on poxviruses, filoviruses, and equine encephalitis viruses (EEV). We discuss the benefits and technical challenges in the current development strategies and the hurdles in the licensure path for MCMs against these highly pathogenic viruses under the FDA Animal Rule, and we provide recommendations for the path forward.

show abstract

“…The resulting "humanized" antibodies contained 90-95% human sequences [24][25][26][27]. Numerous clinical studies have confirmed that humanized antibodies are less immunogenic and more therapeutic in humans than murine or chimeric antibodies [28,29].…”

Section: Chimeric Humanized and Human Mabsmentioning

confidence: 99%

Opportunities and Challenges of Therapeutic Monoclonal Antibodies as Medical Countermeasures for Biodefense

Hu¹,

Nagata²

2016

J Bioterror Biodef

View full text Add to dashboard Cite

Antibodies, naturally produced in the body as part of the immune response to infectious agents, can also be introduced artificially to treat infectious diseases. Advances in biotechnology in the last decades have made human or humanized monoclonal antibodies (mAbs) as therapeutics possible. These therapeutic mAbs currently enjoy unprecedented success and recognition of their potential. Unlike vaccines, therapeutic mAbs can confer instant and consistent protection against bio-threat agents when administered regardless of the recipient's immune status. Therapeutic mAbs can be administered in higher levels than those elicited by vaccines, and thus provide a higher level of protection or treatment that is necessary in a biological attack where people are exposed to a higher exposure of agent concentration than that found in nature. Furthermore, therapeutic mAbs have substantial advantages over antimicrobial drugs, such as high specificity, low systemic toxicity, relatively long half-life, and no concerns over disrupting the body's microbiome. Therapeutic mAbs can be used for both pre-and post-exposure protection; therefore, they have great value as effective medical countermeasures (MedCMs) against bio-threat agents. However, there are still some challenges to be overcome before therapeutic mAbs become ideal MedCMs against bio-threat agents. In this review, both opportunities and challenges in development of therapeutic mAbs are discussed.

show abstract

A recombinant humanized monoclonal antibody completely protects mice against lethal challenge with Venezuelan equine encephalitis virus

Cited by 25 publications

References 32 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

State-of-the-Art Therapeutic Medical Countermeasures for Viral Threat Agents

Opportunities and Challenges of Therapeutic Monoclonal Antibodies as Medical Countermeasures for Biodefense

Contact Info

Product

Resources

About