IMMUNE-RESPONSES AGAINST MAJOR OUTER-MEMBRANE ANTIGENS OF NEISSERIA-MENINGITIDIS IN VACCINEES AND CONTROLS WHO CONTRACTED MENINGOCOCCAL DISEASE DURING THE NORWEGIAN SEROGROUP-B PROTECTION TRIAL

Sera from vaccinees and controls who contracted serogroup B meningococ cal disease during the blinded and open parts of a two-dose protection trial in Norway were compared for antigen-specific and bactericidal a ntibodies against vaccine strain 44/76 (B:15:P1.7,16). From 16 of 20 ( 80%) vaccinees and 26 of 35 (74%) controls, one or more serum samples (n = 104) were collected during the acute phase (1 to 4 days), early c onvalescent phase (5 to 79 days), and late convalescent phase (8 to 31 months) after onset of disease. Binding of immunoglobulin G (IgG) to the major outer membrane antigens (80- and 70-kDa proteins, class 1, 3 , and 5 proteins, and lipopolysaccharide [LPS]) on immunoblots was mea sured by digital image analysis. Specific IgG levels in vaccinees incr eased from acute to early convalescent phases, followed by a decline, while controls showed a small increase over time. Vaccinees had signif icantly higher levels than controls against class 1 and 3 porins and L PS in acute sera, against all antigens during early convalescence, and against class 1 and 3 porins in the later sera, Vaccinees who were in fected with strains expressing subtype P1,7,16 proteins demonstrated a level of IgG binding to protein P1,7,16 with early-convalescent-phase sera that was fourfold higher than that of those infected with other strains. Bactericidal titers in serum against the vaccine strain were 192-fold higher for vaccinees than those for controls during early con valescence, but similarly low levels were found during late convalesce nce. A vaccine-induced anamnestic response of specific and functional antibody activities was thus shown, but the decrease in protection ove r time after vaccination indicated that two vaccine doses did not indu ce sufficient levels of long-term protective antibodies.