Accumulating scientific evidence suggests different profiles

Accumulating scientific evidence suggests different profiles of each IgG subclass in protection against pathogens. Human IgG1 is the most dominant subclass in human sera and generally plays an important role in the protection against a variety of viral infections. In addition to inactivation and/or inhibition of the pathogenicity by direct interaction with target molecules, IgG1 and IgG3 have the ability to activate subsequent host immune responses, such as complement pathways, Fcγ receptor-mediated immune responses, and antibody-dependent cellular cytotoxicity. Such arms of responses are shown to significantly contribute to the elimination of pathogens and inactivation of pathogenic factors and some reports suggest that IgG3 has the strongest effector functions among all IgG subclasses (Cao et al., 2013; Hofmeister et al., 2011; Irani et al., 2015; Scharf et al., 2001; Natsume et al., 2008; Stapleton et al., 2011). With regard to the kinetics of the trans-placental transfer of maternal lenvatinib to the fetus, the efficiency of the IgG transport by neonatal Fc receptor (FcRn) in the placenta seems to marginally depend on its subclasses, i.e., a little higher efficiency for IgG1 and a little lower efficiency for IgG2, but is significantly reduced due to maternal diseases such as placental malaria or hyperglobulinemia, in which the transfer of IgG1 and IgG2 but not that of IgG3 is impaired (Hamilton, 1987; Okoko et al., 2001). A past clinical study focused on the comparison of levels of RSV-specific IgG1 and IgG3 in patients, and its results suggested that the avidity of IgG1 against the whole RSV protein correlates with the protection against RSV infection in infants <3months old. The correlation between avidity of IgG3 and protection against RSV infection was hardly characterized because of lower concentrations of IgG3 as compared with IgG1 (Freitas et al., 2011). Here, in order to examine the dynamics of human immune responses against acute RSV infections, we designed a clinical study targeting 2 different age segments (child patients <3years old and adult patients) and obtained blood samples in both the acute and convalescent phases. Based on quantitative and qualitative multivariate analyses of the immune response against RSV, age-specific profiles and maturation of antibody responses were elucidated. Such results will significantly contribute to the design of RSV vaccines, i.e., adding adjuvants in the formulation and/or selection of the optimal route of administration to overcome the immaturity of immune responses in infants, and to their clinical evaluation by harnessing such parameters as biomarker candidates for determining efficacies of vaccines containing F protein antigen.
Materials and Methods
Results
Discussion This is the study to perform quantitative and qualitative multivariate analyses of antibody responses to RSV and F protein. The results suggested that children\'s antibody responses to RSV are matured over months and years in at least 5 stages: 1st stage responses where IgG3 for F protein is significantly induced but levels of IgG3 for F protein in the convalescent phase (F IgG3 C) are low in infants at to 3months old; 2nd stage responses where F IgG3 C levels are average and GMRs C/A of NT, F IgG1, and F IgG2 levels are low in infants at 4 to 6months old; 3rd stage responses where F IgG3 C levels are high, GMRs C/A of NT, F IgG1, and F IgG2 levels are high, and the antibody affinity maturation and the cross reactivity of IgG for G proteins of groups A and B are induced in infants at 7months and older; 4th stage responses where low levels of neutralization epitope-specific IgG are induced in children at 13 to 18months old; 5th stage responses where levels of NT, F IgG1, F IgG2, F neutralization epitope-specific IgG, and F IgGk in the convalescent phase are high after repetitive RSV infections in children 19months and older (Table 4).