Quantitative and Qualitative-analysis of Antitetanus Toxoid Antibody-response In the Elderly - Humoral Immune-response Enhancement By Thymostimulin

In order to explore the humoral primary and secondary response to tetanus toxoid (TT), and to define the possible immunopotentiating effect of the thymic hormone thymostimulin, we studied 13 elderly people, selected according to the Senieur Eurage protocol, vaccinated against TT, an antigen never encountered before. Six of them were treated with thymostimulin before and during the immunization protocol. Specific anti-TT antibody level measurement and spectrotypic analysis were performed on the sera collected from the subjects at different times over the immunization protocol. In addition, spontaneous in vitro production of anti-TT antibodies as well as cutaneous delayed hypersensitivity reactions were also studied. Only one patient showed a detectable humoral immune response after the first immunization. After the booster, four of six thymostimulin-treated individuals, compared with only two of seven controls, showed in vivo anti-TT humoral response; at the same time, spontaneous anti- TT production was detected in peripheral blood mononuclear cells from five of six thymostimulin-treated individuals but only three of seven untreated controls. These differences were highly significant (p < 0.0001). In addition, only in thymostimulin-treated subjects were the levels of serum anti- TT antibodies 14, 21 and 28 days after the booster significantly (p < 0.05) higher than the baseline values. The spectrotypic analysis of anti-TT antibodies performed by isoelectric focusing and reverse blotting showed total agreement with the' results from enzyme-linked immunosorbent assay. Cutaneous testing to recall antigens showed that among the thymostimulin-treated subjects four of six converted from negative to positive cutaneous reactions (only one to TT antigen). These four were also responders for anti-TT antibodies. In the control group, only one patient converted from cutaneous negativity to positivity for one antigen other than TT (p < 0.0001). This observation suggests that the immunopotentiating effect of thymostimulin is via the T-helper network. In conclusion, this study demonstrates the adjuvant effect of thymostimulin in the specific T-cell dependent antibody response and emphasizes the necessity to consider a cycle of treatment with immunostimulants in elderly people undergoing specific vaccinations, and the importance of the search for biological adjuvants in the construction of new vaccines.