Respiratory Syncitial Virus (RSV)
Respiratory virus infections represent a significant health problem and economic burden throughout the world. Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection worldwide. Virtually all children are infected with RSV by the age of 2 and 1-2% of all infected children require hospitalization. It is believed that RSV infection accounts for 100,000 hospitalizations and 4,500 deaths annually in the United States alone. A formalin-inactivated (FI) RSV vaccine developed in the 1960’s caused augmented disease and increased mortality among some of the infant vaccine recipients upon a subsequent natural infection with RSV. In addition, RSV infection of children has been implicated in the development of asthma later in life. Despite the significant health and economic burden RSV causes, a safe and effective RSV vaccine has yet to be developed. In addition, the only currently approved antiviral therapies are expensive and less than 100% effective in preventing RSV-associated hospitalizations.
In order for a more safe and effective RSV vaccine to be developed, a better understanding of the immune determinants of disease must first be established. The enhanced disease exhibited by the children that received the FI-RSV vaccine can be simulated in a mouse model of RSV infection. Studies using inbred mice have suggested that a subset of CD4 T cells are responsible for mediating the RSV vaccine-enhanced disease. My laboratory is interested in determining mechanisms of how these RSV-specific CD4 T cells mediate RSV vaccine-enhanced disease. The goal of these analyses is to further our understanding of the cellular factors that contribute to RSV vaccine-enhanced disease and provide novel and valuable information necessary for the development of a safe and effective RSV vaccine or immune intervention.