LYMPHOCYTIC 2',5'-OLIGOADENYLATE SYNTHETASE-ACTIVITY INCREASES PRIOR TO THE APPEARANCE OF NEUTRALIZING ANTIBODIES AND IMMUNOGLOBULIN-M AND IMMUNOGLOBULIN-G ANTIBODIES AFTER PRIMARY AND SECONDARY IMMUNIZATION WITH YELLOW-FEVER VACCINE

Primary and secondary immunizations with live, attenuated yellow fever virus vaccine (17D strain) were performed in order to study the cours e of appearance of virus-neutralizing antibodies and immunoglobulin M (IgM) and IgG antibodies directed against the virus and the interferon -dependent enzyme 2',5'-oligoadenylate synthetase (2',5' AS) activity, determined in homogenates of peripheral B and T lymphocytes. From cel lular ATP, this enzyme generates 2',5'-oligoadenylates which mediate d egradation of viral mRNA by stimulation of a latent RNase. By day 4 af ter the first immunization, the earliest and highest 2',5' AS activity was present in the T-lymphocyte fraction, By day 7, the enzyme activi ty was highest in the B-lymphocyte fraction. Virus-neutralizing antibo dies appeared on day 7, and IgM antibodies were present on day 12. Aft er the second immunization, performed 2 years +/- 2 months later, the only significant increase in 2',5' AS activity was observed in the T-l ymphocyte fraction. Virus-neutralizing antibodies were present from da y 1, whereas no IgM antibodies were detected. By day 12, 80% of the va ccinees were IgG positive. In the primary and secondary (memory) immun e responses, 2',5' AS activity is expressed in the T-lymphocyte fracti on prior to the appearance of antibodies directed against the virus an d may serve as an early and sensitive marker of an ongoing virus infec tion which is otherwise difficult to detect. No changes in conventiona l laboratory analysis parameters, such as in differential blood cell c ounts or total IgA, IgG, and IgM, disclosed the immune activity in eit her the primary or the secondary immunization.