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Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
A potential therapeutic neutralization monoclonal antibody specifically against multi-coxsackievirus A16 strains
Ruixiao Du1, Qunying Mao1, Yalin Hu2
1National Institutes for Food and Drug Control , Beijing , China.
Abstract:
Coxsackievirus A16 (CA16) has caused worldwide epidemics of hand, foot and mouth disease (HFMD), particularly in infants and pre-school children. Currently, there are no vaccines or antiviral drugs available for CA16-associated disease. In this study, a CA16-specific monoclonal antibody (MAb) NA11F12 was derived with an epidemic CA16 strain (GenBank no. JX127258). NA11F12 was found to have high cross-neutralization activity against different CA16 subgenotypes but not EV71 using RD cells. The neutralizing titers of NA11F12 ranged from 1:1024 to 1:12288 against A, B1, B2 and C subgenotypes of CA16 and was less than 8 against EV71 strain. In the neonatal mouse model, a single treatment of NA11F12 showed effective protection with a dose- and time-dependent relationship against lethal challenge by CA16 strain (GenBank no. JX481738). At day 1 post-infection, administering more than 0.1 μg/g of NA11F12 could protect 100% newborn mice from mobility and mortality challenged by CA16. With dose of 10 μg/g of NA11F12, a single administration fully protected mice against CA16-associated disease within 4 days post-infection. And there were 80% and 60% mice protected by administering NA11F12 at day 5 post-infection and day 6 post-infection when the control mice had shown clinical symptoms for 1- and 2-day, respectively. Immunohistochemical and histological analysis confirmed that NA11F12 significantly prohibited CA16 VP1 expression in various tissues and prevented CA16-induced necrosis. In conclusion, a CA16-specific MAb NA11F12 with high cross-neutralization activity was identified, which could effectively protect lethal CA16 challenge in mice. It could be a potential therapeutic MAb against CA16 in the future.
Insights
A new monoclonal antibody, NA11F12, shows strong neutralizing activity against Coxsackievirus A16 (CA16), the cause of hand, foot, and mouth disease (HFMD). This antibody effectively protected mice from lethal CA16 infection, offering potential as a future therapy.
Area of Science:
- Virology
- Immunology
- Therapeutics
Background:
- Coxsackievirus A16 (CA16) causes widespread hand, foot, and mouth disease (HFMD) epidemics, particularly in young children.
- No specific vaccines or antiviral treatments currently exist for CA16-related illnesses.
Purpose of the Study:
- To develop and characterize a CA16-specific monoclonal antibody (MAb) for potential therapeutic use.
- To evaluate the neutralizing activity and protective efficacy of the MAb NA11F12 against CA16.
Main Methods:
- Derivation of a CA16-specific MAb (NA11F12) using an epidemic CA16 strain.
- Assessment of NA11F12 cross-neutralization activity against CA16 subgenotypes and EV71 in RD cells.
- Evaluation of NA11F12 protective efficacy in a neonatal mouse model challenged with CA16.
- Immunohistochemical and histological analyses to confirm MAb's mechanism of action.
Main Results:
- NA11F12 demonstrated high neutralizing titers against various CA16 subgenotypes (1:1024 to 1:12288) but not against EV71.
- A single dose of NA11F12 provided dose- and time-dependent protection against lethal CA16 challenge in neonatal mice.
- Treatment with NA11F12 significantly inhibited viral protein expression and prevented tissue necrosis in infected mice.
Conclusions:
- A potent CA16-specific monoclonal antibody, NA11F12, with broad cross-neutralization was identified.
- NA11F12 offers significant protection against lethal CA16 infection in a preclinical mouse model.
- This MAb represents a promising candidate for future therapeutic development against CA16-associated diseases.
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