Pre-existing immunity provides a barrier to airborne transmission of influenza viruses

Abstract

Human-to-human transmission of influenza viruses is a serious public health threat, yet the precise role of immunity from previous infections on the susceptibility to airborne viruses is still unknown. Using human seasonal influenza viruses in a ferret model, we examined the roles of exposure duration and heterosubtypic immunity on influenza transmission. We found that airborne transmission of seasonal influenza strains is abrogated in recipient animals with pre-existing nonneutralizing immunity, indicating that transmissibility of a given influenza virus strain should be examined in the context of ferrets that are not immunologically naïve.

Asynchrony between virus diversity and antibody selection limits influenza virus evolution

“…Despite these high doses, two of the challenge subjects had neither detectable virus nor seroconversion. Similarly, ferret experiments (Le Sage et al, 2020) found that many experienced ferrets developed sufficiently sterilizing immunity to prevent the virus from ever being detected, while some experienced ferrets showed briefly detectable infections that were then cleared. While we cannot rule out a powerful immediate cellular response that was differentially evaded in the various subjects, we believe that our model, coupled with existing understanding of the timing of cellular responses and the speed of influenza virus replication, provides a more parsimonious explanation.…”

“…Currently, empirical evidence for antibody protection at the point of transmission is mostly indirect. Most of this evidence comes from human and animal challenge studies (Clements et al, 1986;Memoli et al, 2020;Le Sage et al, 2020). In these studies, individuals who are challenged with the same antigenic variant sometimes display apparent sterilizing immunity, but other times develop detectable infections.…”

“…In human kinetics data (Hadjichrysanthou et al, 2016) and animal transmission experiments in which one animal infects another (Le Sage et al, 2020;Canini et al, 2020) it is common to see clearly single-peaked infections.…”

“…We hypothesized that influenza virus antigenic evolution is limited by asynchrony between virus diversity and antibody-mediated selection pressure. Antibody immunity at the point of transmission in previously-infected or vaccinated individuals should reduce the initial probability of reinfection (Le Sage et al, 2020); secretory IgA antibodies on mucosal surfaces (sIgA) are likely to play a large role (Wang et al, 2017, see Appendix Section A2). But if viruses are not blocked at the point of transmission and successfully infect host cells, an antibody-mediated recall response takes multiple days to mount (Coro et al, 2006;Lam and Baumgarth, 2019, see detailed review in Appendix Section A2).…”

Asynchrony between virus diversity and antibody selection limits influenza virus evolution

“…We hypothesized that influenza virus antigenic evolution is limited by asynchrony between virus diversity and antibody-mediated selection pressure. Antibody immunity at the point of transmission in previously-infected or vaccinated individuals should reduce the initial probability of reinfection ( Le Sage et al, 2020 ); secretory IgA antibodies on mucosal surfaces (sIgA) are likely to play a large role ( Wang et al, 2017 , see Appendix Section A2). But if viruses are not blocked at the point of transmission and successfully infect host cells, an antibody-mediated recall response takes multiple days to mount ( Coro et al, 2006 ; Lam and Baumgarth, 2019 , see detailed review in Appendix Section A2).…”