Serotype Replacement in Invasive Pneumococcal Disease: Where Do We Go from Here?

Conjugate vaccines have been an impressive addition to our arsenal of weapons against infection. Polysaccharide antigens alone are not good at eliciting a long-lasting immune response, particularly in infants as maternally derived immunity wanes. By coupling or conjugating polysaccharide antigens to protein antigens,we can effectively draw them to the immune system's attention, allowing us to target bacterial pathogens expressing polysaccharide capsules, such as Neisseria meningitidis and Haemophilus influenzae, and, just as importantly, to do so in the vulnerable pediatric host population [1]. In 2000, a pneumococcal conjugate vaccine (PCV7) was introduced against Streptococcus pneumoniae, the pneumococcus, covering 7 of the serotypes most commonly recovered from patients with invasive disease in the United States. In early trials, PCV7 demonstrated >95% efficacy against invasive disease due to vaccine serotypes [2]. Given the leading role of the pneumococcus in infant meningitis and other life-threatening diseases, not to mention its contribution as a cause of less severe but common conditions, such as otitis media (for which the efficacy of PCV7 was significant but much lower than that for more-severe conditions), it was all but inevitable that the new advance would be greeted with wild enthusiasm. The vaccine has been such a turning point in preventing pneumococcal disease that it is now commonplace to refer to the prevaccine and postvaccine "eras" [3–6]