EARLY HIGH-AFFINITY NEUTRALIZING ANTIVIRAL IGG RESPONSES WITHOUT FURTHER OVERALL IMPROVEMENTS OF AFFINITY

Affinity maturation of IgG antibodies in adaptive immune responses is a well-accepted mechanism to improve effector functions of IgG within 2 weeks to several months of antigen encounter. This concept has been defined mainly for IgG responses against chemically defined haptens. W e have evaluated this concept in a viral system and analyzed neutraliz ing IgG antibody responses against vesicular stomatitis virus (a close relative of rabies virus) with a panel of monoclonal antibodies obtai ned early (day 6 or 12) and late (day 150) after hyperimmunization. Th ese neutralizing IgG antibodies recognize a single major antigenic sit e with high affinities (K-a of 10(8)-10(10) liter mol(-1)) and with ra pid on-rates already on day 6 of a primary response and with no eviden ce for further antigen dose- and time-dependent overall improvement of affinity. This type of IgG response is probably representative for vi ruses or bacterial toxins which are crucially controlled by neutralizi ng antibodies.