---
title: "C1q interaction enhances monoclonal antibody protection against lethal HSV-1 in neonatal mice"
id: "biorxiv-4-interaction-with-complement-factor-c1q-can-contribute-to-and-improve-monoclonal"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-4-interaction-with-complement-factor-c1q-can-contribute-to-and-improve-monoclonal"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.19.760222v1?rss=1"
published_at: "2026-10-24T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# C1q interaction enhances monoclonal antibody protection against lethal HSV-1 in neonatal mice
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-4-interaction-with-complement-factor-c1q-can-contribute-to-and-improve-monoclonal
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.19.760222v1?rss=1)
- **Published At:** 2026-10-24T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Investigators used Fc engineering to modify monoclonal antibodies (mAbs) targeting glycoprotein D and glycoprotein B of **HSV-1** to probe complement contributions in vivo. - Two Fc variants were introduced: a complement-enhancing mutation (E430G, EG) and a complement-abrogating mutation (K322A, KA); the source reported these specific substitutions. - In vitro characterization confirmed that antigen recognition was preserved across Fc-modified mAbs while complement activity was selectively increased with EG or reduced with KA, according to the authors. - The study employed a neonatal mouse lethal **HSV-1** infection model to assess protection conferred by the mAb panel; the source named this model but did not report dosing or detailed challenge parameters. - In vivo results showed that altering complement engagement changed the protective capacity of select mAbs, with effects that varied by antibody specificity and target antigen. - The cohort-level data indicated that complement does not act as a uniform determinant of mAb efficacy; rather, complement activity interacts with intrinsic antibody properties to shape antiviral protection. - Authors reported that these findings establish complement-mediated activity, including interaction with **C1q**, as an important component of antibody function in **HSV-1** infection and suggested **Fc engineering** as a strategy to optimize therapeutics. - The source noted patent disclosures and funding sources; it did not provide detailed quantitative efficacy metrics, survival curves, or statistical values in the abstract and public record provided here. - Remaining questions listed by the study team include how broadly complement modulation will affect diverse mAbs and what specific antibody features determine complement-dependence; the source did not report next regulatory milestones.
## Clinical Analysis & Structured Key Points
Interaction with complement factor C1q can contribute to and improve monoclonal antibody-mediated protection against lethal HSV-1 challenge | bioRxiv Skip to main content New Results Interaction with complement factor C1q can contribute to and improve monoclonal antibody-mediated protection against lethal HSV-1 challenge Lesle M Jimenez , Matthew D Slein , David A Leib , View ORCID Profile Margaret E Ackerman doi: https://doi.org/10.64898/2026.10.19.760222 Lesle M Jimenez Dartmouth College Find this author on Google Scholar Find this author on PubMed Search for this author on this site Matthew D Slein Dartmouth College Find this author on Google Scholar Find this author on PubMed Search for this author on this site David A Leib Dartmouth College Find this author on Google Scholar Find this author on PubMed Search for this author on this site Margaret E Ackerman Dartmouth College Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Margaret E Ackerman For correspondence: margaret.e.ackerman{at}dartmouth.edu Abstract Info/History Metrics Supplementary material Preview PDF 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. Competing Interest Statement DAL and MEA report a patent, WO2020077119A1, for the use of HSV-specific mAbs as method for the treatment for nHSV infections. MEA reports consulting for Seromyx Systems and research funding from Moderna unrelated to this work. Funder Information Declared National Institutes of Health , R01AI176646 , R21AI195395 , T32AI007363 Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license . Back to top Previous Next Posted October 24, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Interaction with complement factor C1q can contribute to and improve monoclonal antibody-mediated protection against lethal HSV-1 challenge Message Subject (Your Name) has forwarded a page to you from bioRxiv Message Body (Your Name) thought you would like to see this page from the bioRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Interaction with complement factor C1q can contribute to and improve monoclonal antibody-mediated protection against lethal HSV-1 challenge Lesle M Jimenez , Matthew D Slein , David A Leib , Margaret E Ackerman bioRxiv 2026.10.19.760222; doi: https://doi.org/10.64898/2026.10.19.760222 Share This Article: Copy Citation Tools Interaction with complement factor C1q can contribute to and improve monoclonal antibody-mediated protection against lethal HSV-1 challenge Lesle M Jimenez , Matthew D Slein , David A Leib , Margaret E Ackerman bioRxiv 2026.10.19.760222; doi: https://doi.org/10.64898/2026.10.19.760222 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8164) Biochemistry (19027) Bioengineering (15171) Bioinformatics (45345) Biophysics (22958) Cancer Biology (20115) Cell Biology (27308) Clinical Trials (138) Developmental Biology (14146) Ecology (21400) Epidemiology (2067) Evolutionary Biology (25811) Genetics (16343) Genomics (23841) Immunology (19027) Microbiology (43196) Molecular Biology (18345) Neuroscience (95083) Paleontology (713) Pathology (3034) Pharmacology and Toxicology (5200) Physiology (8284) Plant Biology (16271) Scientific Communication and Education (2116) Synthetic Biology (4646) Systems Biology (10386) Zoology (2427)
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