The mechanism(s) of immunity to Respiratory Syncytial Virus (RSV) infection, including the possible role of serum antibody in protection from severe lower respiratory tract involvement, is poorly defined. Although animal studies demonstrate a protective effect of serum antibody, seroepidemiologic studies of infected infants have gone no further than to suggest an inverse relationship between both incidence and severity of illness and the level of circulating RSV antibody. Two envelope glycoproteins, GP90 and VP70, mediate infectivity and spread of RSV; GP90 mediates attachment of virus while VP70, the RSV fusion protein, mediates cell-to-cell spread of virus by syncytium formation. An antigen-specific protective antibody profile has so far not been defined. Although antibody to either envelope glycoprotein neutralizes virus, only antibody to the fusion protein can prevent cell-to-cell spread of infection. The presence of neutralizing antibody directed against GP90 alone, therefore, may be insufficient for protection from severe disease whereas antibody to VP70 alone might be sufficient since it can mediate both neutralization and inhibition of fusion. The major aims of this study will be to: (1) test the hypothesis that the level of antibody to VP70 in acute serum is inversely correlated with severity of disease, and that a defined level of antibody to VP70 offers protection from severe lower respiratory disease with RSV infection; and (2) test the hypothesis that a specific level of antibody to VP70 and GP90 is necessary to prevent infection with RSV. In addition, this study will (3) determine the antigen-specific (GP90, VP70 and NP44, the nucleocapsid protein) class-specific (IgG, M, A) antibody response to both mild and severe infection with RSV, and (4) measure the antigen-specific class-specific antibody profile present at birth and document its natural decline with age. The data obtained from this information will have direct applicability to the development and use of newer RSV vaccines, especially purified protein products.
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