DIFFICULTIES IN ESTABLISHING A SEROLOGICAL CORRELATE OF PROTECTION AFTER IMMUNIZATION WITH HAEMOPHILUS-INFLUENZAE CONJUGATE VACCINES

In several studies the protective concentration of anti-Haemophilus influenzae type b (Hib) capsular polysaccharide (PS) antibodies has been concluded to be around 0.04 to 0.20 mu g/ml. After the Finnish Hib polysaccharide vaccine trial it was estimated that 1 mu g/ml has to be achieved to predict long term protection after vaccination. These estimates of protective anti-Hib PS antibody concentrations were based on the assumption that protection from invasive Hib disease is mediated by antibodies and the role of cell-mediated immunity is negligible. This assumption was justified since the Hib PS is a T cell-independent antigen. The matter becomes quite different when the character of the PS vaccine is altered by conjugating it to a protein carrier, so that it acquires the ability to stimulate T cells, and the immunological memory plays a role in the protection. The immunized infants are thought to be able to respond with a rapid and high antibody response after exposure to the organism. After immunization with conjugate vaccines, protection can be seen at a lower serum antibody concentration than after polysaccharide vaccine. In addition, higher avidity of anti-Hib PS antibodies is associated with the response to conjugate than PS vaccine, and there are differences between the conjugates. This might have an influence on the functional activity of the antibodies. Hib conjugate vaccines are also able to reduce the carriage rate of Hib. This should be kept in mind when estimating what is needed from protective immune response after immunization with Hib conjugate vaccines.