New technologies in therapeutic antibody development: The next frontier for treating infectious diseases

Keating, Sheila M.; Higgins, Brett W.

doi:10.1016/j.antiviral.2024.105902

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article1

Preprint1

Relationship

Self Cite0

Independent2

Authors

Journals

Cited by 2 publications

References 121 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

High-throughput specificity profiling of antibody libraries using ribosome display and microfluidics

Wagner,

Carter,

Lim

et al. 2024

Cell Reports Methods

View full text Add to dashboard Cite

High-throughput specificity profiling of antibody libraries using ribosome display and microfluidics

Wagner,

Carter,

Lim

et al. 2024

Cell Reports Methods

View full text Add to dashboard Cite

Improving antibody-mediated protection against HSV infection by eliminating interactions with the viral Fc receptor gE/gI

Slein,

Backes,

Kelkar

et al. 2024

Preprint

View full text Add to dashboard Cite

Herpes simplex virus (HSV) encodes surface glycoproteins that are host defense evasion molecules, allowing the virus to escape immune clearance. In addition to their role in neuropathogenesis and cell-cell spread, glycoproteins E and I (gE/gI) form a viral Fc receptor (vFcR) for most subclasses and allotypes of human IgG and promote evasion of humoral immune responses. While monoclonal antibodies (mAbs) protect mice from neonatal HSV (nHSV) infections, the impact of the vFcR on mAb-mediated protection by binding to IgG is unknown. Using HSV-1 with intact and ablated gE-mediated IgG Fc binding, and Fc-engineered antibodies with modified ability to interact with gE/gI, we investigated the role of the vFcR in viral pathogenesis and mAb-mediated protection from nHSV. The gD-specific human mAb HSV8 modified to lack binding to gE exhibited enhanced neutralization and in vivo protection compared to its native IgG1 form. This improved protection by the engineered mAbs was dependent on the presence of the vFcR. Human IgG3 allotypes lacking vFcR binding also exhibited enhanced antiviral activity in vivo, suggesting that vaccines that robustly induce IgG3 responses could show enhanced protection, suggesting the value of vaccination strategies that robustly induce this subclass. Lastly, analysis of longitudinal responses to acute primary genital infection in humans raised the possibility that unlike most viruses, HSV may exhibited slow induction of IgG3. In summary, this study demonstrates that mAbs lacking the ability to interact with the vFcR can exhibit improved protection from HSV - offering new prospects for antibody-based interventions.

show abstract

New technologies in therapeutic antibody development: The next frontier for treating infectious diseases

Cited by 2 publications

References 121 publications

High-throughput specificity profiling of antibody libraries using ribosome display and microfluidics

High-throughput specificity profiling of antibody libraries using ribosome display and microfluidics

Improving antibody-mediated protection against HSV infection by eliminating interactions with the viral Fc receptor gE/gI

Contact Info

Product

Resources

About