Pathogen evolution, selection and immunity

Lineup of example pathogens

Questions for groups to address

  1. Dengue: What is antibody dependent enhancement? What is the evidence that it occurs in dengue infections? And why does dengue in particular show antibody dependent enhancement? How does antibody dependent enhancement relate to the antigenic diversity of dengue serotypes?
  2. Enterovirus: Are there multiple strains of enterovirus that are antigenically distinct? What determines the timing of EV outbreaks caused by different strains (e.g., CV-A16 and EV-A71)? Enterovirus D68 is thought to be related to development of acute flaccid myelitis. What is the relationship of EV-D68 to other enteroviruses and why would EV-D68 in particular be linked to AFM?
  3. HIV: What strain dynamics occur during untreated chronic infection? Describe the interplay between adaptive immunity and HIV within-host evolution.
  4. Malaria: How does antigen switching promote prolonged infections of Plasmodium parasites? What are the within-host dynamics in which parasites presenting different antigens cycle?
  5. Norovirus: Specific clades, called “genotypes” in the norovirus literature, show seasonal dominance. What is driving genotype dominance? And how does dominant genotype vary from season to season?
  6. Pertussis: How is immunity to pertussis affected by the route of exposure (natural infection v. immunization with the cellular or acellular vaccine)? Is there evidence of vaccine-driven evolution?
  7. Streptococcus pneumoniae: How has serotype diversity been affected by the introductions of the pneumococcal conjugate vaccines? How has vaccine-associated selection affected the evolution of antibiotic resistance in pneumococcus?
  8. Neisseria gonorrhoeae: What drives balancing selection on antibiotic resistance in gonococcus? How does the mode of transmission shape bacterial population structure?
  9. Swine flu: Human seasonal influenza viruses are continually introduced into domestic swine populations. However, human-derived swine flu evolves more slowly in pigs. Why is this? Is this an expected outcome from models of antigenic drift?
  10. Measles: Why does measles virus show very little if any antigenic drift despite mutating rapidly at the RNA level?
  11. SARS-CoV-2: What is driving the emergence of variant of concern (VOC) and variant of interest (VOI) viruses? Why were these not observed in the initial spring and summer 2020 pandemic waves?
  12. SARS-CoV-2: How much of increased fitness as inferred by regional dominance of variant of concern (VOC) and variant of interest (VOI) viruses is due to increased intrinsic transmissibility and how much is due to antigenic drift?
  13. SARS-CoV-2: What strategies should we pursue in choosing which variant to target with an updated vaccine? Are there other vaccine strategies that may lead to more robustness against continued antigenic evolution?
  14. SARS-CoV-2: Do we expect Original Antigenic Sin (OAS) to become an issue that eventually limits vaccine efficacy to an evolving SARS-CoV-2 virus?