Impaired gamma interferon responses against parvovirus B19 by recently infected children

Parvovirus B19 is the causative agent of "fifth disease" of childhood. It h as been implicated in a variety of conditions, including unsuccessful pregn ancy and rheumatoid arthritis, and is a potential contaminant of blood prod ucts, There has been little study of immunity to parvovirus B19, and the ex act nature of the protective humoral and cell-mediated immune response is u nclear. Immune responses to purified virus capsid proteins, VP1 and VP2, we re examined from a cohort of recently infected children and compared with r esponses from long-term convalescent volunteers. The results demonstrate th at antibody reactivity is primarily maintained against conformational epito pes in VP1 and VP2. The unique region of VPI appears to be a major target f or cell-mediated immune responses, particularly in recently infected indivi duals. We confirm that antibody reactivity against linear epitopes of VP2 i s lost shortly after infection but find no evidence of the proposed phenoty pic switch in either the subclass of parvovirus B19-specific antibody or th e pattern of cytokine production by antigen-specific T cells. The dominant subclass of specific antibody detected from both children and adults was im munoglobulin G1. No evidence was found for interleukin 4 (IL-4) or IL-5 pro duction by isolated lymphocytes from children or adults, In contrast, lymph ocytes from convalescent adults produced a typical type 1 response associat ed with high levels of IL-2 and gamma interferon (IFN-gamma). However, we o bserved a significant (P < 0.001) deficit in the production of IFN-gamma in response to VP1 or VP2 from lymphocytes isolated from children. Taken toge ther, these results imply that future parvovirus B19 vaccines designed for children will require the use of conformationally preserved capsid proteins incorporating Th1 driving adjuvants. Furthermore, these data suggest novel mechanisms whereby parvovirus B19 infection may contribute to rheumatoid a rthritis and unsuccessful pregnancy.