Cell-mediated immune responses to respiratory syncytial virus infection Magnitude, kinetics, and correlates with morbidity and age

We evaluated the cell-mediated immune (CMI) response to RSV acute infection including the magnitude, kinetics and correlates with morbidity and age. Twenty-nine RSV-infected patients with mean +/- SD age of 15 +/- 14 months were enrolled during their first week of disease. Th1, Th2, Th9, Th17 and Th22 responses were measured at entry and 2 and 6 weeks later. All subjects were hospitalized for a median (range) of 5 (3-11) days. RSV-specific effector and memory Th1 CMI measured by lymphocyte proliferation and IFN gamma ELISPOT significantly increased over time (P <= 0.03). In contrast, Th22 responses decreased over time (P <= 0.03). Other changes did not reach statistical significance. The severity of RSV disease measured by the length of hospitalization positively correlated with the magnitude of Th9, Th22 and TNF alpha inflammatory responses (rho >= 0.4; P <= 0.04) and negatively with memory CMI (rho = -0.45; P = 0.04). The corollary of this observation is that robust Th1 and/or low Th9, Th22, and TNF alpha inflammatory responses may be associated with efficient clearance of RSV infection and therefore desirable characteristics of an RSV vaccine. Young age was associated with low memory and effector Th1 responses (rho >= 0.4; P <= 0.04) and high Th2, Th9, Th17, Th22 and TNF alpha inflammatory responses (rho <= -0.4; P <= 0.04), indicating that age at vaccination may be a major determinant of the CMI response pattern.