# Enhancing the structural stability of P29-targeted monoclonal antibodies via β-hydroxybutyrylation modification improves their therapeutic performance in alveolar echinococcosis

## TL;DR

Researchers improved a monoclonal antibody for treating alveolar echinococcosis by modifying it with β-hydroxybutyrylation, which increased its stability and effectiveness.

## Contribution

β-hydroxybutyrylation modification is introduced as a novel strategy to enhance antibody stability and therapeutic efficacy in parasitic diseases.

## Key findings

- Modified antibody retained high antigen-binding affinity (KD = 343 pM) and showed increased resistance to proteolytic degradation.
- P29 mAbKbhb significantly inhibited protoscolex regeneration and induced apoptosis in a murine model of AE.
- The modification improved serum persistence by 1.75-fold after 5 weeks.

## Abstract

Alveolar echinococcosis (AE), a severe parasitic infection often likened to "parasitic cancer", still lacks effective treatments. Although our earlier ork on the P29 monoclonal antibody (P29 mAb) against the parasite-derived P29 antigen showed potential, its efficacy remained limited, prompting the need for improved biologic agents.

We applied β-hydroxybutyrylation (Kbhb) modification to engineer an enhanced antibody, P29 mAbKbhb, and comprehensively evaluated its properties using surface plasmon resonance, protease resistance assays, pharmacokinetic studies in C57BL/6 mice, and histopathological analysis of alveolar hydatid cysts.

The modified antibody retained high antigen-binding affinity (KD = 343 pM) and exhibited markedly increased resistance to proteolytic degradation, with a 1.75-fold improvement in serum persistence after 5 weeks. Furthermore, in a murine model of AE, P29 mAbKbhb significantly inhibited protoscolex regeneration and induced apoptosis of cyst wall cells relative to the unmodified antibody.

Our results establish a novel connection between protein engineering and antiparasitic therapy, illustrating that Kbhb modification not only augments the efficacy of anti-AE antibodies but also offers a versatile strategy for enhancing antibody stability and half-life. This offers a potential strategy for developing new treatments against neglected zoonotic diseases via tailored post-translational modifications.