Editorial Commentary: Fifteen Years of Protection by Meningococcal C Conjugate Vaccines: Lessons From Disease Surveillance

Despite the extensive advances that have been made in biomedical sciences in the past few decades, the development and implementation of novel vaccines remains a highly pragmatic and uncertain endeavor. Although the concept of vaccination is >200 years old and was formalized by Pasteur >100 years ago, progress in the development of vaccines remains comparatively slow and has not accelerated in the way seen in virtually all other areas of technology. The many reasons for this include safety concerns arising from the administration of vaccinations to otherwise healthy individuals, often infants or children, and our inability to predict reliably the behavior of a novel human vaccine at the population level from data gathered in laboratory experimentsorevenduringphase I orphase II trials of human subjects [1]. Although large placebo-controlled double-blind phase III trials can provide useful information in both regards, these are very expensive, prohibitively so if the disease is rare, and evenvery large studiesmaybe insufficiently powered to detect population effects [1]. It is often the case, therefore, that vaccines are introduced without full knowledge of their likely impact, particularly without knowledge of how population effects might be best exploited in vaccination schedules. Consequently, it is important to ensure that enhanced disease surveillance is in place before, during, and after any vaccine introduction to evaluate vaccine impact post hoc and enable immunization schedules to be modified as necessary. Two articles in this issue [2, 3], describing the effectiveness of meningococcal serogroup C conjugate (MCC) vaccines during a 15-year period in the Netherlands and Canada, demonstrate the lasting value of such surveillance data in understanding how a vaccine works. They further illustrate how such information can be used to refine and improve implementation, even years after vaccine introduction. For MCC vaccines this was especially important, because no phase III efficacy trials had been conducted before implementation. Compared with many of the current challenges in vaccinology [1], vaccines against the serogroup C meningococcus presented a relatively straightforward problem [4]. The expression of a capsular polysaccharide is strongly associated with the invasive phenotype in meningococci, with only a subset of the 12 known capsular variants (those corresponding to serogroups A, B, C, W, X, and Y) responsible for most epidemic and endemic disease [5]. Good antibody responses against capsular antigens were demonstrated to be important in protection against meningococcal disease in the 1960s [6], and the development of protein-polysaccharide conjugation technology in the 1980s [7] resulted in very safe, well-tolerated vaccines that were capable of eliciting strong anamnestic antibody responses. The successful implementation of the Haemophilus influenzae type b vaccines in the early 1990s provided evidence of the utility of such vaccines [8], paving the way for the development and implementation of highly effective meningococcal vaccines [9]. In most high-income countries, and many lowand middle-income countries outside the African meningitis belt, meningococcal disease is rare, with periods of low incidence punctuated by increased incidence, which may include localized disease outbreaks or hyperendemics [5]. For reasons that remain unclear, during the 1990s there were sharp increases in the number of cases of serogroup C disease caused by meningococci belonging to the hyperinvasive sequence type 11 complex in a number of countries. These increases were especially troubling Received 15 July 2014; accepted 17 July 2014; electronically published 28 July 2014. Correspondence: Martin C. J. Maiden, BSc, PhD, FRCPath, FSB, Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK ([email protected]). Clinical Infectious Diseases 2014;59(9):1222–4 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons. org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. DOI: 10.1093/cid/ciu599