Therapeutic and prophylactic treatment with a virus-specific antibody is highly effective in rodent models of Chikungunya infection and disease

Julander, Justin G.; Anderson, Nicole; Haese, Nicole; Andoh, Takeshi F.; Streblow, Daniel N.; Cortez, Pierre; Carter, Kara; Marniquet, Xavier; Watson, Hugh; Mandron, Marie

doi:10.1016/j.antiviral.2022.105295

Cited by 5 publications

(7 citation statements)

References 23 publications

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“…Development of new interventions usually involves use of mouse models as early evaluation tools. Although a number of animal models have been described (10)(11)(12), the non-lethal, adult C57BL/6J mouse model of viremia and arthritic foot swelling (13)(14)(15) has been widely adopted internationally (16)(17)(18)(19)(20)(21)(22)(23). This model has been used to investigate the virology, immunobiology and immunopathology of CHIKV infections (12,14,(24)(25)(26)(27)(28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model

et al. 2022

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IntroductionAn adult wild-type C57BL/6J mouse model of chikungunya virus (CHIKV) infection and disease has been extensively used to study the alphaviral arthritic immunopathology and to evaluate new interventions. How well mouse models recapitulate the gene expression profiles seen in humans remains controversial.MethodsHerein we perform a comparative transcriptomics analysis using RNA-Seq datasets from the C57BL/6J CHIKV mouse model with datasets obtained from adults and children acutely infected with CHIKV.ResultsDespite sampling quite different tissues, peripheral blood from humans and feet from mice, gene expression profiles were quite similar, with an overlap of up to ≈50% for up-regulated single copy orthologue differentially expressed genes. Furthermore, high levels of significant concordance between mouse and human were seen for immune pathways and signatures, which were dominated by interferons, T cells and monocyte/macrophages. Importantly, predicted responses to a series of anti-inflammatory drug and biologic treatments also showed cogent similarities between species.DiscussionComparative transcriptomics and subsequent pathway analysis provides a detailed picture of how a given model recapitulates human gene expression. Using this method, we show that the C57BL/6J CHIKV mouse model provides a reliable and representative system in which to study CHIKV immunopathology and evaluate new treatments.

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Section: Introductionmentioning

confidence: 99%

Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model

et al. 2022

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“…It was effective in preventing disease in mice when administered up to 4 weeks prior to the virus challenge. CHIKVinfected mice treated with mAb were resistant to the secondary challenge, and no evidence of ADE was detected [121].…”

Section: Chikungunya Virus (Chikv)mentioning

confidence: 97%

“…The E2 protein is a major target for mAbs, and some mAbs were thus developed: 4N12 [115], SVIR023 [121] and DC2.271B [116].…”

Section: Chikungunya Virus (Chikv)mentioning

confidence: 99%

Development of Therapeutic Monoclonal Antibodies for Emerging Arbovirus Infections

Ormundo,

Barreto,

Tsuruta

2023

Viruses

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Antibody-based passive immunotherapy has been used effectively in the treatment and prophylaxis of infectious diseases. Outbreaks of emerging viral infections from arthropod-borne viruses (arboviruses) represent a global public health problem due to their rapid spread, urging measures and the treatment of infected individuals to combat them. Preparedness in advances in developing antivirals and relevant epidemiological studies protect us from damage and losses. Immunotherapy based on monoclonal antibodies (mAbs) has been shown to be very specific in combating infectious diseases and various other illnesses. Recent advances in mAb discovery techniques have allowed the development and approval of a wide number of therapeutic mAbs. This review focuses on the technological approaches available to select neutralizing mAbs for emerging arbovirus infections and the next-generation strategies to obtain highly effective and potent mAbs. The characteristics of mAbs developed as prophylactic and therapeutic antiviral agents for dengue, Zika, chikungunya, West Nile and tick-borne encephalitis virus are presented, as well as the protective effect demonstrated in animal model studies.

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“…It was effective in preventing disease in mice when administered up to 4 weeks prior to the virus challenge. CHIKV-infected mice treated with mAb were resistant to the secondary challenge, and no evidence of the ADE was detected [121].…”

Section: Mabs For Chikvmentioning

confidence: 97%

“…The E2 protein is a major target for mAbs and some mAbs were developed: 4N12 [115], SVIR023 [121] and DC2.271B [116].…”

Section: Mabs For Chikvmentioning

confidence: 99%

Development of Therapeutic Monoclonal Antibodies for the Emerging Arbovirus Infections

Ormundo,

Barreto,

Tsuruta

2023

Preprint

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Antibody-based passive immunotherapy has been used effectively in the therapy and prophylaxis of infectious diseases. Outbreaks of the emerging viral infections from arthropod-borne viruses (arboviruses) represent a global public health problem due to the rapid spread and urge actions and treatment of the infected individuals to combat them. Preparedness in advance developing antivirals and studies related to the epidemiology could protect us from damages and losses. Immunotherapy based on monoclonal antibodies (mAbs) has shown to be very specific to combat infectious diseases and several illnesses. Recent advances in the mAb discovery techniques allowed the development and approval of a wide number of therapeutic mAbs. This review focuses on the technological approaches available to select neutralizing mAbs for emerging arbovirus infections and outstanding strategies to obtain highly effective and potent mAbs. The characteristics of mAbs developed as prophylactic and therapeutic antiviral agents for the dengue, Zika, chikungunya and West Nile virus are presented, as well as the protective effect verified in animal model studies.

show abstract

Therapeutic and prophylactic treatment with a virus-specific antibody is highly effective in rodent models of Chikungunya infection and disease

Cited by 5 publications

References 23 publications

Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model

Chikungunya patient transcriptional signatures faithfully recapitulated in a C57BL/6J mouse model

Development of Therapeutic Monoclonal Antibodies for Emerging Arbovirus Infections

Development of Therapeutic Monoclonal Antibodies for the Emerging Arbovirus Infections

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