Potent Protection against H5N1 and H7N9 Influenza via Childhood Hemagglutinin Imprinting

By Katelyn M. Gostic, Monique Renee Ambrose, Michael Worobey, James O. Lloyd-Smith. 2016

446 citations recorded by the source corpus.

Lifelong protection against severe influenza The first influenza attack that a child suffers can affect the way that their lifelong immunity to the virus builds up. A wide range of influenza A virus subtypes infect humans. Subtype H5 belongs to HA group 1 (which also includes H1 and H2 subtypes), and subtype H7 belongs to HA group 2 (which also includes the H3 subtype). Gostic et al. found that birth-year cohorts that experienced first infections with seasonal H3 subtype viruses were less susceptible to the potentially fatal avian influenza H7N9 virus (see the Perspective by Viboud and Epstein). Conversely, older individuals who were exposed to H1 or H2 subtype viruses as youngsters were less susceptible to avian H5N1-bearing viruses. A mathematical model of the protective effect of this imprinting could potentially prove useful to predict the age distribution and severity of future pandemics. Science, this issue p. 722; see also p. 706 Cross-protective immunity occurs between seasonal and potentially pandemic avian influenza and protects against severe disease. Two zoonotic influenza A viruses (IAV) of global concern, H5N1 and H7N9, exhibit unexplained differences in age distribution of human cases. Using data from all known human cases of these viruses, we show that an individual’s first IAV infection confers lifelong protection against severe disease from novel hemagglutinin (HA) subtypes in the same phylogenetic group. Statistical modeling shows that protective HA imprinting is the crucial explanatory factor, and it provides 75% protection against severe infection and 80% protection against death for both H5N1 and H7N9. Our results enable us to predict age distributions of severe disease for future pandemics and demonstrate that a novel strain’s pandemic potential increases yearly when a group-mismatched HA subtype dominates seasonal influenza circulation. These findings open new frontiers for rational pandemic risk assessment.

Subfields: Epidemiology, Infectious Diseases

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In Epidemiology

1. Barney S. Graham
2. Trevor Bedford
3. Jesse D. Bloom
4. D. Veesler
5. M. Kanekiyo

In Infectious Diseases

1. D. Veesler
2. David Baker
3. Young-Jun Park
4. Jesse D. Bloom

Citations in the corpus

• Glycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses (2020, background): “Immunological imprinting from early-life exposures has also been implicated to have a substantial impact on skewing subsequent immune response to influenza virus potentially for life 61, 62 .”
• Elicitation of broadly protective immunity to influenza by multivalent hemagglutinin nanoparticle vaccines (2020, background): “69 ), human clinical trials will be needed to assess the impact of complex and individualized influenza exposure histories and immunological imprinting 70,71 ​ .”
• Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and Unexposed Individuals (2020, unknown): “Cross-reactive immunity to influenza strains has been modeled to be a critical influencer of susceptibility to newly emerging, potentially pandemic, influenza strains (Gostic et al., 2016).”
• Next-Generation Influenza Vaccines. (2020, background): “Immunological imprinting has been shown to affect subsequent immunity to heterosubtypic influenza viruses on a HA group-specific bias (Gostic et al. 2016).”
• Adaptive immunity to SARS-CoV-2 and COVID-19 (2021, unknown): “Finally, while cross-reactive memory B cells are rare in adults, imprinting of antibody responses based on memory B cells to related viruses may impact protective immunity (Aydillo et al.; Gostic et al., 2016).”
• Mapping person-to-person variation in viral mutations that escape polyclonal serum targeting influenza hemagglutinin (2019, background): “These ferrets have typically been infected just once with a single viral strain—unlike humans, who have complex exposure histories that may influence their antibody response (Li et al., 2013; Linderman et al., 2014; Andrews et al., 2015b; Gostic et al., 2016; Cobey and Hensley, 2017).”
• Design of Nanoparticulate Group 2 Influenza Virus Hemagglutinin Stem Antigens That Activate Unmutated Ancestor B Cell Receptors of Broadly Neutralizing Antibody Lineages (2018, unknown): “Immunological imprinting from earlier 367 or first exposures has also been suggested to play a significant role in shaping the subsequent 368 immune response to influenza (45, 46).”