Vaccines for the unvaccinated: protecting the herd.

Interrupting the transmission of infectious agents by introducing new vaccines into a population and creating herd immunity has proven to be a remarkable hidden genie for vaccine effectiveness. For example, oneto two-thirds of the effectiveness of the bacterial conjugate vaccines is linked to protection of the unvaccinated. However, the mechanisms of herd immunity are often not well understood, it is poorly predicted and/or considered in licensure or implementation strategies for new vaccines, and the longterm consequences of preventing natural exposure to agents covered by vaccine are not known. Defining, quantifying, and monitoring the impact of herd immunity is becoming increasingly important for analyses of vaccine effectiveness and cost effectiveness and for decisions about vaccine introduction and use. In this issue of the Journal, Maiden et al. [1] report on the impact of meningococcal serogroup C polysaccharide conjugate vaccines on the prevalence of meningococcal carriage, herd immunity, and meningococcal disease in the United Kingdom. In one of the largest multicenter meningococcal carriage studies ever performed, 48,309 samples from students were obtained during a 2-year period after vaccine was introduced (2000 and 2001). A total of 8599 meningococcal isolates were recovered and characterized by genotyping and phenotyping. A significant and specific reduction in the prevalence of serogroup C meningococcal carriage was noted that lasted at least during the 2 years of the study, without evidence of new meningococcal serogroup replacement. Vaccine efficacy against serogroup C carriage was at least 75%, with a high impact on the virulent clonal complex of serogroup C meningococci associated with invasive meningococcal disease. The decreases in the prevalence of carriage correlated with reductions in serogroup C meningococcal disease in unvaccinated individuals; at least 50% of the effectiveness of the meningococcal serogroup C conjugate vaccines is due to herd immunity [2], and the impact of herd immunity against this serogroup has lasted for years [3]. Herd immunity has long been recognized as an important benefit of vaccines. Vaccines against diphtheria poliovirus, varicella, rubella, measles, hepatitis B virus, Bordetella pertussis, and a variety of veterinary pathogens have important herd immunity effects, and herd immunity is being emphasized as an important strategy against influenza [4]. Largely unanticipated at the time of vaccine introduction, the herd immunity effect of the bacterial polysaccharide conjugate vaccines has been a major contributor to the successful control of invasive and noninvasive disease due to Haemophilus influenzae type b (Hib), major serotypes of Streptococcus pneumoniae, and Neisseria meningitidis serogroup C. The dramatic herd immunity impact of the Hib conjugate vaccines (accounting for one-third of the 95% reduction in invasive Hib disease [5]) and the meningococcal serogroup C conjugate vaccines has been established. Other important examples include the effect on the incidence of invasive pneumococcal disease in unvaccinated children and adults that results from administering the heptavalent pneumococcal conjugate vaccine to infants and young children (69% of cases prevented through indirect effects [6]) and the role of the pneumococcal conjugate vaccines in reducing influenzaassociated morbidity [7]. The study by Maiden et al. [1] and other recent studies [3, 5, 8 –11, 12, 13] provide additional lessons about how herd immunity and bacterial polysaccharide conjugate vaccines work together, as well as information about the limitations of herd immunity . However, many questions remain to be answered. How should these vaccines be introduced to maximize and maintain effectiveness through individual and herd immunity (e.g., should Received 14 November 2007; accepted 15 November 2007; electronically published 13 February 2008. Potential conflicts of interest: D.S.S. reports grant funding from GlaxoSmithKline for studies of lipooligosaccharide and from the National Institutes of Health for studies of pneumococcal antibiotic resistance mechanisms and meningococcal pathogenesis. He also reports having served as a consultant to the Meningitis Vaccine Project, the Food and Drug Administration, the Centers for Disease Control and Prevention (CDC), and Novartis, and serving on the CDC/Advisory Committee on Immunization Practices meningococcal working group. Reprints or correspondence: David S. Stephens MD, Emory University, School of Medicine, 1648 Pierce Drive, NE, Atlanta Georgia, 30322 ([email protected]). The Journal of Infectious Diseases 2008; 197:643–5 © 2008 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2008/19705-0004$15.00 DOI: 10.1086/527402 E D I T O R I A L C O M M E N T A R Y