title: The evolutionary consequences of blood-stage vaccination on the rodent malaria Plasmodium chabaudi.
abstract: Malaria vaccine developers are concerned that antigenic escape will erode vaccine efficacy. Evolutionary theorists have raised the possibility that some types of vaccine could also create conditions favoring the evolution of more virulent pathogens. Such evolution would put unvaccinated people at greater risk of severe disease. Here we test the impact of vaccination with a single highly purified antigen on the malaria parasite Plasmodium chabaudi evolving in laboratory mice. The antigen we used, AMA-1, is a component of several candidate malaria vaccines currently in various stages of trials in humans. We first found that a more virulent clone was less readily controlled by AMA-1-induced immunity than its less virulent progenitor. Replicated parasites were then serially passaged through control or AMA-1 vaccinated mice and evaluated after 10 and 21 rounds of selection. We found no evidence of evolution at the ama-1 locus. Instead, virulence evolved; AMA-1-selected parasites induced greater anemia in naïve mice than both control and ancestral parasites. Our data suggest that recombinant blood stage malaria vaccines can drive the evolution of more virulent malaria parasites.
authors.affiliation: Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, University Park, Pennsylvania, United States of America. vcb11@psu.edu
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Barclay
authors.forename: Derek
authors.initials: D
authors.lastname: Sim
authors.forename: Brian H K
authors.initials: BH
authors.lastname: Chan
authors.forename: Lucas A
authors.initials: LA
authors.lastname: Nell
authors.forename: Maia A
authors.initials: MA
authors.lastname: Rabaa
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Bell
authors.forename: Robin F
authors.initials: RF
authors.lastname: Anders
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Read
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D001483:Base Sequence; D016054:DNA, Protozoan / Q000032:analysis / Q000235:genetics*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D019143:Evolution, Molecular; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D016788:Plasmodium chabaudi / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D012692:Serial Passage; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D016054:DNA, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium