An attempt at an epidemiological explanation - Epib.nl

General discussionBrazilian study, however, showed poor reactions in younger children. The Chileanvaccine provided low-level protection only.20 The efficacy of the vaccine in theNorwegian trial among teenagers was 57%, and the authors concluded that the effectwas insufficient to justify a public vaccination prograrnme. 22 In regard of the varietyof subtypes among serogroup B isolates in the Netherlands, a multivalent OMPvaccine will be needed in this country. The cbanges in the distribution of sub typesamong serogroup B meningococci, in concert with the rapidly occurring phenotypicchanges of a clone, require adaptation of such an OMP vaccine from time to time,and a periodical revaccination of (some of) the population with the adapted vaccinewill probably be necessary. In this respect, the occurrence of an epidemic due to ameningococcal clone with a new virulent subtype bas to be feared. Because theincrease in frequency of the new subtype P1.4 in the Netherlands during the 1980swas gradual, it would have been possible to adapt the vaccine. Further research onth e development of multivalent OMP vaccines is needed, and because of the apparentage-dependent efficacy of the previously tested vaccines, phase III trials of thesevaccines should be conducted among infants as well.During tbe study period, the annual proportion of nonsubtypeable serogroup Bmeningococci varied from 12% to 26% (Cbapter 2). In order not to be surprised bythe recrudescence of a meningococcal strain with a yet unknown subtype, furtherdevelopment of new monoclonal class 1 specific antibodies is needed in order to beable to recognize as many subtypes as possible, so that they can eventually beincluded in the vaccine.The meningococcal class 1 OMP harbours 2 variable regions (VRI and VR2)wbich determine 2 mutually exclusive sets of subtypes." The epitopes that determinethe subtypes P1.5, P1.7, and P1.l2 are located in VRl, and the epitopes of tberemaining subtypes in VR2. Each meningococcus that has a class 1 OMP sbouldtherefore express a subtype combination. 111e subtype combinations P1.7,1, P1.7,16,P1.5,2 and Pl.12,16 are well known. However, the majority of the meningococcianalysed expressed a single subtype (Chapter 2) and sbould, therefore, be consideredpartly nonsubtypeable. Part of this nonsubtypeability might be explained by so-called"hidden epitopes". The existence of a hidden P1.7 epitope has been demonstrated forisolates of the sub types Pl.16 25 and Pl.4 (Poolman et af. unpublished observations).Furtber research on the existence of other hidden epitopes, and the role of theseepitopes in eliciting protective antibodies, is needed.Another matter of concern are meningococci that do not express a class 1 OMP invitro. It has been estimated that approximately 3% of all serogroup B isolates submittedto the RLBM in 1990 did not express a class 1 OMP, and the suggestion wasput forward that this phenomenon could also occur in vivo, which might interfere withthe class 1 specific immunity." The potential absence of a class 1 OMP, tbe variety ofsubtypes among serogroup B meningococci and the experience of the previous OMPvaccination trials, require further research on other serogroup B vaccine candidates.One of tbese is the lipooligosaccbaride (LOS) moiety of tbe outer membrane of meningococci.17 18 27 A limited number of different immunotypes was found among sero-91