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Published on: June 16, 2011
Selection of coxsackievirus B4 variants with monoclonal antibodies results in attenuation
Abstract:
Inoculation of suckling mice with coxsackievirus B4 (CB4) results in the death of a majority of the animals. In this study we selected antigenic variants of CB4 in the presence of neutralizing monoclonal antibodies and tested them to see whether they were attenuated. Antigenic variants selected with a single antibody showed little or no attenuation by producing a high mortality (60 to 100%). A double variant selected with two antibodies showed considerable attenuation by causing only 25% mortality. A triple variant selected with three antibodies was almost completely attenuated (killed only 5% of the animals). Polypeptides from these variants were tested for their ability to interact with the monoclonal antibodies used for their selection. These studies showed that resistance of variant virus to neutralization in general was due to the inability of the antibody to bind to the virus. However, one of the antibodies could bind but not neutralize the virus, perhaps due to an alteration in the epitope. It is concluded that selection of CB4 variants using more than one neutralizing monoclonal antibody can lead to attenuation of the virus.
Insights
Selecting coxsackievirus B4 (CB4) variants with multiple neutralizing monoclonal antibodies significantly attenuates the virus. This approach reduces mortality in mice, offering a potential strategy for developing safer viral strains.
Area of Science:
- Virology
- Immunology
Background:
- Coxsackievirus B4 (CB4) infection in suckling mice leads to high mortality.
- Neutralizing monoclonal antibodies are crucial tools for studying viral evasion mechanisms.
Purpose of the Study:
- To investigate the attenuation of coxsackievirus B4 (CB4) by selecting antigenic variants using neutralizing monoclonal antibodies.
- To assess the correlation between the number of antibodies used for variant selection and the degree of viral attenuation.
Main Methods:
- Selection of CB4 antigenic variants in the presence of single, double, and triple neutralizing monoclonal antibodies.
- Assessment of viral attenuation by determining mortality rates in inoculated suckling mice.
- Analysis of polypeptide-antibody interactions to understand neutralization resistance.
Main Results:
- Single antibody-selected variants showed minimal attenuation with 60-100% mortality.
- Double antibody-selected variants demonstrated considerable attenuation, resulting in 25% mortality.
- Triple antibody-selected variants exhibited near-complete attenuation, with only 5% mortality.
- Resistance to neutralization was primarily due to antibodies failing to bind the virus, though one antibody showed altered binding without neutralization.
Conclusions:
- Selection of CB4 variants using multiple neutralizing monoclonal antibodies effectively attenuates the virus.
- The degree of attenuation is positively correlated with the number of antibodies used in the selection process.
- Understanding antibody-epitope interactions is key to developing attenuated viral strains.
