Antibody Escape Mutations in Respiratory Syncytial Virus
Additional Funding Sources
The project described was supported by an EPSCoR Track-2 Award from the National Science Foundation under Grant Number OIA-1736253.
Abstract
Respiratory syncytial virus (RSV) is an intracellular pathogen that infects people of all ages. RSV is responsible many deaths each year and currently, there is no licensed vaccine. In an alternate form of therapy, monoclonal antibodies can be used to treat infection by neutralizing the virus. We want to investigate the ability of RSV to mutate under stress of a human monoclonal antibody, D25. We hypothesized that RSV will mutate under stress of a sub-inhibitory dose of D25 resulting in escape from neutralization. Molecular modeling done by our collaborators will also accurately predict these mutations. To test this, we introduced RSV to rounds of selection in the presence of D25 and allowed time for mutations to arise. After ten rounds of selection in HEp-2 cells, viral mutants required significantly more antibody for neutralization. The mutants will be sequenced for specific amino acid changes and will be compared to the modeled predictions. These results will help us better understand how RSV evolves to escape neutralization.
Antibody Escape Mutations in Respiratory Syncytial Virus
Respiratory syncytial virus (RSV) is an intracellular pathogen that infects people of all ages. RSV is responsible many deaths each year and currently, there is no licensed vaccine. In an alternate form of therapy, monoclonal antibodies can be used to treat infection by neutralizing the virus. We want to investigate the ability of RSV to mutate under stress of a human monoclonal antibody, D25. We hypothesized that RSV will mutate under stress of a sub-inhibitory dose of D25 resulting in escape from neutralization. Molecular modeling done by our collaborators will also accurately predict these mutations. To test this, we introduced RSV to rounds of selection in the presence of D25 and allowed time for mutations to arise. After ten rounds of selection in HEp-2 cells, viral mutants required significantly more antibody for neutralization. The mutants will be sequenced for specific amino acid changes and will be compared to the modeled predictions. These results will help us better understand how RSV evolves to escape neutralization.
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