Vaccination against colonizing bacteria with multiple serotypes

Abstract

Conjugate vaccines protect vaccinated individuals against both disease from and nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae. Protection is specific to the capsular serotype(s) included in the vaccine. This specificity has raised concern that vaccination against particular (“targeted”) serotypes may cause an increase in carriage of (and diseases attributable to) nontargeted serotypes. I analyzed a mathematical model designed to predict the factors affecting, and the expected extent of, such replacement in the host population. The conditions for competitive exclusion and coexistence of serotypes under mass vaccination are derived, and the equilibrium carriage of target and nontarget serotypes is determined under various ecological and epidemiological conditions. The eradication threshold for a target serotype in the presence of competing, nontarget serotypes is always lower for serotype-specific than for bivalent vaccines. In a two-serotype model, the increase in the prevalence of any single nontargeted serotype due to vaccination will not exceed the total reduction in prevalence of a targeted serotype. However, if three or more serotypes interact epidemiologically, vaccination against one type may increase carriage of a second more than it decreases carriage of the first. Carriage of a second serotype against which the vaccine offers only partial protection may initially increase and then decrease as a function of vaccine coverage. I discuss the extent to which these theoretical results can account for existing data on serotype replacement after vaccination against H. influenzae and their implications for vaccine policy.