CYTOTOXIC T-LYMPHOCYTE PRECURSOR FREQUENCIES IN BALB C MICE AFTER ACUTE RESPIRATORY SYNCYTIAL VIRUS (RSV) INFECTION OR IMMUNIZATION WITH A FORMALIN-INACTIVATED RSV VACCINE/

A better understanding of the immune response to live and formalin-ina ctivated respiratory syncytial virus (RSV) is important for developing nonlive vaccines. In this study, major histocompatibility complex (MH C) class I- and II-restricted, RSV-specific cytotoxic T-lymphocyte pre cursor (CTLp) frequencies were determined in bronchoalveolar lavage (B AL) samples and spleen lymphocytes of BALB/c mice intranasally infecte d with live RSV or intramuscularly inoculated with formalin-inactivate d RSV (FI-RSV), After RSV infection, both class I- and class Ii-restri cted CTLps were detected by day 4 or 5 postinfection (p.i.), Peak CTLp frequencies were detected by day 7 p.i, The class II-restricted CTLp frequencies in the BAL following RSV infection were less than class I- restricted CTLp frequencies through day 14 p.i., during which class I- restricted CTLp frequencies remained elevated, but then declined by 48 days p.i. The frequencies of class II-restricted CTLps in the BAL wer e 2- to 10-fold less than those of class I-restricted CTLps. For splee n cells, frequencies of both MHC class I- and II-restricted CTLps to l ive RSV were similar. In contrast, class II-restricted CTLps predomina ted in FI-RSV-vaccinated mice. RSV challenge of vaccinated mice result ed in an increase in the frequency of class I-restricted CTLps at day 3 p.i. but did not enhance class II-restricted CTLp frequencies. These studies demonstrate differences in the CTLp response to live RSV infe ction compared with FI-RSV immunization and help define possible mecha nisms of enhanced disease after FI-RSV immunization. In addition, thes e studies provide a quantitative means to address potential vaccine ca ndidates by examining both MHC class I- and II-restricted CTLp frequen cies.