Ronald Guderian

Impaired Tetanus-Specific Cellular and Humoral Responses following Tetanus Vaccination in Human Onchocerciasis: A Possible Role for Interleukin-10

Onchocerca volvulus infection has been associated with impaired cellular responses to parasite antigens, an impairment that may also extend to nonparasite antigens. To investigate the mechanism of this impaired immune response, the effect of concurrent O. volvulus infection on the immune response to tetanus toxoid (TT) following tetanus vaccination was studied. The proliferative, cytokine, and antibody response to TT of O. volvulus-infected subjects (n = 19) and comparable noninfected controls (n = 20) were studied before and 6 months after vaccination with TT. Following vaccination, antibody levels, proliferative responses, and levels of interferon-gamma were significantly greater in noninfected subjects (P < .05, .001, and .05, respectively); however, infected subjects produced interleukin-10, but noninfected controls did not (P < .001). These studies indicate that concurrent infection with O. volvulus can diminish the immune response to an unrelated antigen (TT) by a mechanism that is likely to involve interleukin-10.

Isotype-specific characterization of antibody responses to Onchocerca volvulus in putatively immune individuals.

Isotypejsubclass‐specific antibody responses to adult Onchocerca volvulus extract (OvAg) were assessed by both ELISA and immunoblotting for a group of putatively immune individuals (PIs, n = 29) from a hyperendemic area in Ecuador and for a group of infected individuals (INFs, n = 47) from the same region. As a group, the Pis have been previously shown to possess lower levels of OvAg specific IgG1, IgG2, IgG3 and IgG4 than INFs but semiquantitative analysis revealed that the relative proportions of these subclasses differs between the two groups. The IgG of the PI group contained a higher proportion of IgG3 and a lower proportion of IgG4 than the INF group. The frequency distribution of IgG3 responses was similar for the PI and INF groups. The frequency distributions for IgG1, IgG4 and IgE were significantly different between the PI and INF groups. A subgroup of the Pis were identified from frequency distributions and multivariate plots of individual isotype responses as having antibody responses (mainly IgG4) possibly indicative of cryptic infection. High IgE responses were exclusive to INF individuals, and a rare response type of high IgG3 with negligible levels of other isotypes/subclasses was seen only in the PI group. However, the majority of the Pis had negligible responses for all antibody classes. Immunoblots demonstrated no obvious differences in qualitative recognition between the PIs and INFs.

Heterogeneity of IgG antibody responses to cloned Onchocerca volvulus antigens in microfiladermia positive individuals from Esmeraldas Province, Ecuador

The prevalence of IgG antibodies to three recombinant O. volvulus antigens, OvMBP/10, OvMBP/11 and OvMBP/29 was determined in a group of 94 microfilaria positive (mf+) individuals resident in the hyperendemic onchocercal area of Esmeraldas Province, Ecuador. Clone OvMBP/11 was the antigen most frequently recognized by patients sera followed by OvMBP/10 and OvMBP/29. When a cocktail of the three recombinant antigens was used the proportion of positive sera increased to 100%. Antibody responses to the fusion partner maltose binding protein (MBP) were low in comparison with those to the cloned antigens and no correlation of responses between individual antigens was observed. The relative level of antibody response to each of the clones in the cocktail varied between individuals. The distribution of IgG responses to OvMBP/11 was bimodal and those to OvMBP/29 and OvMBP/10 were positively and negatively skewed, respectively. When the three recombinant antigens were used in combination this variation was minimized and the pattern of responses showed a normal distribution as was also seen to crude O. volvulus antigen. The cocktail of recombinants thus offers excellent diagnostic sensitivity in combination with the parasite specificity demonstrated previously.