lineup

Lineup of example pathogens

• Dengue
• HIV
• Malaria
• Measles
• Norovirus
• Pertussis
• SARS-CoV-2
• Seasonal flu
• Streptococcus pneumoniae
• Swine flu

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. HIV: What strain dynamics occur during untreated chronic infection? Describe the interplay between adaptive immunity and HIV within-host evolution.
3. Malaria: What mechanism promotes antigen switching in prolonged infections of Plasmodium parasites? What are the within-host dynamics that result from these switches in antigen?
4. Measles: Why does measles virus show very little if any antigenic drift despite mutating rapidly at the RNA level?
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. SARS-CoV-2: What drove the emergence of variant of concern (VOC) and variant of interest (VOI) viruses in 2021? Why were these not observed in the initial spring and summer 2020 pandemic waves? Are similar dynamics at play in 2022 and 2023?, Ie are chronic infections still playing an impactful role in the population-level evolution of SARS-CoV-2?
8. 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? Please include Omicron lineages BA.2, BA.5, and XBB in this discussion.
9. 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? Why was a monovalent XBB.1.5 vaccine chosen by the FDA for this fall’s vaccination campaign?
10. Seasonal influenza: The B/Yamagata lineage of seasonal influenza seems to have gone extinct. No sequenced B/Yam viruses have been detected since March 2020. What is your hypothesis for this observation and how could you imagine testing this hypothesis? Why did B/Yam go extinct and not B/Vic or H3N3 or H1N1pdm? What other respiratory pathogens might have gone extinct and why?
11. 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?
12. 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? Given these dynamics, when will swine flu viruses that descend from human H3N2 viruses (as discussed in Nelson et al 2015) become a pandemic risk? Do we expect perhaps similar long-term dynamics at play in white-tailed for SARS-CoV-2?