A bispecific broadly neutralizing antibody against enterovirus 71 and coxsackievirus A16 with therapeutic potential

Area of Science:

• Virology
• Immunology
• Biotechnology

Background:

• Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) are primary pathogens causing hand, foot, and mouth disease (HFMD) globally.
• HFMD frequently leads to severe neurological complications in children.
• Current treatments lack efficacy against simultaneous EV71 and CA16 infections, highlighting an urgent need for new therapeutic strategies.

Purpose of the Study:

• To engineer novel bispecific antibodies for simultaneous neutralization of EV71 and CA16.
• To evaluate the cross-neutralization potency and therapeutic efficacy of engineered bispecific antibodies against EV71 and CA16 infections.

Main Methods:

• Engineered four bispecific antibodies using variable fragments from EV71- and CA16-specific neutralizing monoclonal antibodies (mAbs).
• Assessed cross-reactivity and cross-neutralization capabilities of the engineered antibodies.
• Evaluated the in vivo therapeutic efficacy of the lead bispecific antibody in mouse models of single and mixed EV71/CA16 infections.

Main Results:

• The bispecific antibody Bs(scFv)4-IgG-1 demonstrated significant cross-reactivity against both EV71 and CA16.
• Bs(scFv)4-IgG-1 exhibited enhanced cross-neutralization potency compared to its parental antibodies.
• Bs(scFv)4-IgG-1 achieved 100% therapeutic efficacy in mice infected with single or mixed EV71 and CA16 strains.

Conclusions:

• Bispecific antibody engineering offers a promising approach for developing therapeutics against enteroviral infections.
• Bs(scFv)4-IgG-1 represents a potential curative treatment option for hand, foot, and mouth disease caused by EV71 and CA16.
• This study provides valuable insights for future development of broad-spectrum enterovirus therapies.