= 1.67 0.7) (Fig. specific antibody detected from both children and adults was immunoglobulin G1. No evidence was found for interleukin 4 (IL-4) or IL-5 production by isolated lymphocytes from children or adults. In contrast, lymphocytes from convalescent adults produced a typical type 1 response associated with high levels of IL-2 and gamma interferon (IFN-). However, we observed a significant (< 0.001) deficit in the production of IFN- in response to VP1 or VP2 from lymphocytes isolated from children. Taken together, these results Rabbit polyclonal to AHCYL1 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 arthritis and unsuccessful pregnancy. Human parvovirus B19 OAC2 (B19V) causes the common childhood illness known as fifth disease or erythema infectiosum. While the symptoms are generally mild, there are a variety of conditions under which infection has more severe outcomes. In the immunocompromised or patients with underlying hemolytic disorders, such as sickle-cell disease and hereditary spherocytosis, infection with B19V can result in an acute aplastic crisis or in chronic anemia (39, 53). During pregnancy, the virus can be transmitted transplacentally from an infected mother to the fetus and can cause spontaneous abortion or fetal anemia (9). Direct infection of the fetus can result in nonimmune hydrops fetalis. B19V has also been OAC2 linked to arthritis in adults and children (41). It has been estimated that 60% of women with symptomatic disease manifest arthropathy (53). The symptoms generally subside within 3 weeks, but about 20% of affected women suffer a persistent or recurring arthropathy. At present there is no effective vaccine available either for women of child-bearing age or for the general population. B19V is a small, nonenveloped, single-stranded DNA virus classified as an erythrovirus. OAC2 The virus replicates in human erythroid progenitor cells of the bone marrow and blood, inhibiting erythropoiesis (54). Infection with B19V is common, and upwards of 60 to 70% of the population is seropositive by adulthood (8). Transmission most commonly occurs by personal contact via aerosol or respiratory secretions; however, contaminated blood products may also be a source of iatrogenic transmission. The B19V capsid consists of an 83-kDa minor structural protein, VP1, and a 53-kDa major structural protein, VP2. VP2 makes up about 95% of the total capsid, with VP1 making up the remainder (38). The sequences of the two proteins are colinear, with VP2 being identical to the carboxyl terminus of VP1; however, VP1 contains an additional 227 amino acids unique to the amino-terminal end. Although little is known about the protective immune response against B19V in humans, specific antiviral antibody is considered the major mechanism of protection. This is based on the circumstantial evidence that high-dose immunoglobulin therapy is sometimes beneficial for infected patients (23, 43). This treatment does not work in all cases, and no data is available on the actual protective level of B19V immunoglobulin G (IgG), although levels greater than 6 IU are thought to be protective (44). It has been previously shown that a time-dependent change in antibody response occurs against viral capsid proteins by an unknown mechanism (47). It is characterized by a loss of antibody specificity against linear viral epitopes of VP1 and VP2 and also by a proposed antibody subclass switch from IgG3 to IgG4. It has been speculated that this switch is caused by an underlying alteration in the type of CD4+ T-cell response; however, there has been very little examination of this response in humans (16, 51). It is accepted that in response to antigen, T helper (Th) cells secrete cytokines, OAC2 which are involved in regulatory functions or can mediate direct activity against invading viruses. The current paradigm is that Th cells can be subdivided into at least three populations according to.