title: Controlling antimicrobial resistance through targeted, vaccine-induced replacement of strains.
abstract: Vaccination has proven effective in controlling many infectious diseases. However, differential effectiveness with regard to pathogen genotype is a frequent reason for failures in vaccine development. Often, insufficient immune response is induced to prevent infection by the diversity of existing serotypes present in pathogenic populations of bacteria. These vaccines that target a too narrow spectrum of serotypes do not offer sufficient prevention of infections, and can also lead to undesirable strain replacements. Here, we examine a novel idea to specifically exploit the narrow spectrum coverage of some vaccines to combat specific, emerging multi- and pan-resistant strains of pathogens. Application of a narrow-spectrum vaccine could serve to prevent infections by some strains that are hard to treat, rather than offer the vaccinated individual protection against infections by the pathogenic species as such. We suggest that vaccines targeted to resistant serotypes have the potential to become important public health tools, and would represent a new approach toward reducing the burden of particular multi-resistant strains occurring in hospitals. Vaccines targeting drug-resistant serotypes would also be the first clinical intervention with the potential to drive the evolution of pathogenic populations toward drug-sensitivity. We illustrate the feasibility of this approach by modeling a hypothetical vaccine that targets a subset of methicillin-resistant Staphylococcus aureus (MRSA) genotypes, in combination with drug treatment targeted at drug-sensitive genotypes. We find that a combined intervention strategy can limit nosocomial outbreaks, even when vaccine efficacy is imperfect. The broader utility of vaccine-based resistance control strategies should be further explored taking into account population structure, and the resistance and transmission patterns of the pathogen considered.
authors.affiliation: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, United States of America. ytekle@spelman.edu
authors.forename: Yonas I
authors.initials: YI
authors.lastname: Tekle
authors.forename: Kaare M
authors.initials: KM
authors.lastname: Nielsen
authors.forename: Jingzhou
authors.initials: J
authors.lastname: Liu
authors.forename: Melinda M
authors.initials: MM
authors.lastname: Pettigrew
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Meyers
authors.forename: Alison P
authors.initials: AP
authors.lastname: Galvani
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Townsend
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D003428:Cross Infection / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005838:Genotype; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000276:immunology*; D013203:Staphylococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D013209:Staphylococcal Vaccines / Q000276:immunology*; D014611:Vaccination
chemical_list: D000890:Anti-Infective Agents; D013209:Staphylococcal Vaccines