Interaction with complement factor C1q can contribute to and improve monoclonal antibody-mediated protection against lethal HSV-1 challenge
- 1Dartmouth College
Abstract
Herpes simplex virus (HSV) has extensive strategies to evade host defense, including mechanisms that limit clearance by the complement cascade. Using Fc engineering, we incorporated a complement-enhancing (E430G, EG) or a complement-abrogating mutation (K322A, KA) to a panel of glycoprotein D- and glycoprotein B-specific monoclonal antibodies (mAbs) to assess the role of complement-driven antiviral activity in a neonatal mouse HSV-1 infection model. In vitro characterization confirmed that Fc modifications preserved antigen recognition while selectively amplifying or reducing complement activity. In vivo, complement modulation altered the protective capacity of select mAbs to protect against lethal HSV-1 challenge, demonstrating that complement contributes to antibody-mediated control of HSV-1 infection in an antibody- and antigen-dependent manner. The differential effects observed across the mAb panel indicate that complement activity does not function as a uniform determinant of antibody efficacy, but instead operates in concert with antibody-specific properties to shape antiviral protection. Collectively, these findings establish complement-mediated activity as an important component of antibody function in HSV-1 infection, and highlight Fc engineering as a strategy to optimize antibody-mediated protection. More broadly, these findings underscore the multifaceted nature of antibody-mediated protection and provide a mechanistic framework for considering complement-dependent functions in the development of antibody-based therapeutics.
Related
- Gut complement C1q and C3 interact with Clostridioides difficile spores via CdeM and contribute to pathogenesis.
- Dual-Antigen CCHFV Vaccine Induces Neutralizing Immunity and Protection Against Lethal Challenge
- A preventive LNP-mRNA vaccine encoding a truncated form of OipA conferred protection against Helicobacter pylori challenge in BALB/c mice
- Disrupted FAP-satellite cell communication contribute to maladaptive muscle remodeling in older women
- Non-Coding Structural Variants in Regulatory Regions and High Polygenic Burden May Jointly Contribute to Early-Onset Familial Hashimoto’s Thyroiditis
BibTeX
@misc{jimenez2026interaction,
title = {{Interaction with complement factor C1q can contribute to and improve monoclonal antibody-mediated protection against lethal HSV-1 challenge}},
author = {L. M. Jimenez and M. D. Slein and D. A. Leib and M. E. Ackerman},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.760222},
url = {https://www.biorxiv.org/content/10.64898/2026.10.19.760222v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Interaction with complement factor C1q can contribute to and improve monoclonal antibody-mediated protection against lethal HSV-1 challenge
AU - L. M. Jimenez
AU - M. D. Slein
AU - D. A. Leib
AU - M. E. Ackerman
PY - 2026
DA - 2026/10/19
PB - bioRxiv
DO - 10.64898/2026.10.19.760222
UR - https://www.biorxiv.org/content/10.64898/2026.10.19.760222v1
AB - Herpes simplex virus (HSV) has extensive strategies to evade host defense, including mechanisms that limit clearance by the complement cascade. Using Fc engineering, we incorporated a complement-enhancing (E430G, EG) or a complement-abrogating mutation (K322A, KA) to a panel of glycoprotein D- and glycoprotein B-specific monoclonal antibodies (mAbs) to assess the role of complement-driven antiviral activity in a neonatal mouse HSV-1 infection model. In vitro characterization confirmed that Fc modifications preserved antigen recognition while selectively amplifying or reducing complement activity. In vivo, complement modulation altered the protective capacity of select mAbs to protect against lethal HSV-1 challenge, demonstrating that complement contributes to antibody-mediated control of HSV-1 infection in an antibody- and antigen-dependent manner. The differential effects observed across the mAb panel indicate that complement activity does not function as a uniform determinant of antibody efficacy, but instead operates in concert with antibody-specific properties to shape antiviral protection. Collectively, these findings establish complement-mediated activity as an important component of antibody function in HSV-1 infection, and highlight Fc engineering as a strategy to optimize antibody-mediated protection. More broadly, these findings underscore the multifaceted nature of antibody-mediated protection and provide a mechanistic framework for considering complement-dependent functions in the development of antibody-based therapeutics.
ER -