Richard Neher

Biozentrum & SIB, University of Basel

slides at neherlab.org/202205_Cologne.html

- Birth of immunologically naive individuals
- Waning of pre-existing immunity
- Antigenic change of the virus

- extremely rapid infection of naive children
- long-lived immunity → rare re-infection

- frequent reinfection of adults
- combination of waning and antigenic evolution
- Approximate equilibrium between immunity and infections

- Influenza viruses evolve to avoid human immunity
- Vaccines need frequent updates

- Long list of distances between sera and viruses
- Tables are sparse, only close by pairs

- each branch contributes $d_i$ to antigenic distance
- sparse solution for $d_i$ through $l_1$ regularization

Final susceptibility $S_\infty$: $\log(S_\infty) = - R_0 (S_\infty-1)$

$R_0=2$ → $S_\infty = 0.2$, very small for later $R_0$.

$R_0=2$ → $S_\infty = 0.2$, very small for later $R_0$.

Model with strains $a,b,c,\ldots$:

Infections: $ \frac{d}{dt}I_a = \beta S_a I_a - \nu I_a $

Susceptibilty: $ \frac{d}{dt}S_a = -\nu S_a \sum_{b} K_{ab}I_b $ cross-immunity: $K_{ab}$

Infections: $ \frac{d}{dt}I_a = \beta S_a I_a - \nu I_a $

Susceptibilty: $ \frac{d}{dt}S_a = -\nu S_a \sum_{b} K_{ab}I_b $ cross-immunity: $K_{ab}$

- early large antigenic steps (relative to cross-immunity range) are necessary to persist
- large cross-immunity range is necessary to prevent speciation
- cross-immunity typically has short and long range components

- The Yamagata lineage might have disappeared during the pandemic

- Spanish diversity mirrored in many European countries
- Suggested many introduction with clusters of similar size

→ travel - A transmission advantage would result in a few dominating introductions
- Screening and quarantine system rather leaky

- High incidence differential and high travel volume can drive a variant to dominance
- Travel associated activities and behavior further increases impact
- Onward spread in traveling demographics can be higher

- BA.2 (21L) has essentially taken over.
- BA.4 (22A) and BA.5 (22B) emerged in Southern Africa. Mutations at positions 452 and 486 lead to immune evasion
- BA.2.12.1 (22C) has a mutation at position 452 and is common in the US

- Will we start seeing second and third generation variants, as opposed to sister variants?
- Will we the saltatory dynamics with heavily diverged variants continue?
- Will a more diverse immunity landscape slow down future variant dynamics?
- Will waning/antigenic evolution slow down and give rise to annual or even rarer waves?

- Boris Shraiman
- Colin Russell
- Trevor Bedford
- Pierre Barrat
- Oskar Hallatschek
- All the NICs and WHO CCs that provide influenza sequence data
- The WHO CCs in London and Atlanta for providing titer data

- Emma Hodcroft (now in Bern)
- Moira Zuber (Basel)
- IĆ±aki Comas and Fernando Gonzalez-Candelas, Valencia
- Martina Reichmuth and Christian Althaus (Bern)
- Tanja Stadler, Sarah Nadeau, Tim Vaughan at ETH
- Alberto Hernando and David Matteo at Kido Dynamics
- Jesse Bloom, Katherine Crawford at Fred Hutch
- David Veesler, Alex Walls, Davide Corti, John Bowen at UW