Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution

Huddleston, John; Barnes, John; Rowe, Thomas; Xu, Xinhua; Kondor, Rebecca; Wentworth, David E.; Whittaker, Lynne; Ermetal, Burcu; Daniels, Rodney S.; McCauley, John W.; Fujisaki, Seiichiro; Nakamura, Kenzo; Kishida, Noriko; Watanabe, Shinji; Hasegawa, Hideki; Barr, Ian G.; Subbarao, Kanta; Barrat-Charlaix, Pierre; Neher, Richard A.; Bedford, Trevor

doi:10.7554/elife.60067

Cited by 61 publications

(81 citation statements)

References 48 publications

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“…In supplementary figures S3 and S4 , Supplementary Material online, we repeat this analysis for the best predictors from our recent comparison of predictive models for influenza ( Huddleston et al. 2020 ).…”

Section: Resultsmentioning

confidence: 99%

“…Methods for predicting the future evolution of influenza either construct explicit fitness models ( Luksza and Lässig 2014 ; Huddleston et al. 2020 ), use historical patterns of evolution ( Bush et al.…”

Section: Discussionmentioning

confidence: 99%

“…(2014) ; Neher et al. (2016) ; Huddleston et al. (2020) predict fitness by using hemagglutination inhibition (HI) data to determine possible antigenic drift of clades in the genealogy of the HA protein.…”

Section: Introductionmentioning

confidence: 99%

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Limited Predictability of Amino Acid Substitutions in Seasonal Influenza Viruses

Barrat-Charlaix

Huddleston

Bedford

et al. 2021

Molecular Biology and Evolution

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Seasonal influenza viruses repeatedly infect humans in part because they rapidly change their antigenic properties and evade host immune responses, necessitating frequent updates of the vaccine composition. Accurate predictions of strains circulating in the future could therefore improve the vaccine match. Here, we studied the predictability of frequency dynamics and fixation of amino acid substitutions. Current frequency was the strongest predictor of eventual fixation, as expected in neutral evolution. Other properties, such as occurrence in previously characterized epitopes or high Local Branching Index (LBI) had little predictive power. Parallel evolution was found to be moderately predictive of fixation. While the LBI had little power to predict frequency dynamics, it was still successful at picking strains representative of future populations. The latter is due to a tendency of the LBI to be high for consensus-like sequences that are closer to the future than the average sequence. Simulations of models of adapting populations, in contrast, show clear signals of predictability. This indicates that the evolution of influenza HA and NA, while driven by strong selection pressure to change, is poorly described by common models of directional selection such as travelling fitness waves.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Limited Predictability of Amino Acid Substitutions in Seasonal Influenza Viruses

Barrat-Charlaix

Huddleston

Bedford

et al. 2021

Molecular Biology and Evolution

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“…Second, vaccine strains are selected about six months ahead of implementation because vaccine manufacture and delivery takes several months. In the interim, influenza viruses continue to evolve, so better prediction methods are needed and are being explored 93. Third, most of the global supply of influenza vaccine is manufactured in embryonated chicken eggs.…”

Section: Vaccines For Influenzamentioning

confidence: 99%

Vaccines for older adults

Cunningham

McIntyre

Subbarao

et al. 2021

BMJ

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The proportion of the global population aged 65 and older is rapidly increasing. Infections in this age group, most recently with SARS-CoV-2, cause substantial morbidity and mortality. Major improvements have been made in vaccines for older people, either through the addition of novel adjuvants—as in the new recombinant zoster vaccine and an adjuvanted influenza vaccine—or by increasing antigen concentration, as in influenza vaccines. In this article we review improvements in immunization for the three most important vaccine preventable diseases of aging. The recombinant zoster vaccine has an efficacy of 90% that is minimally affected by the age of the person being vaccinated and persists for more than four years. Increasing antigen dose or inclusion of adjuvant has improved the immunogenicity of influenza vaccines in older adults, although the relative effectiveness of the enhanced influenza vaccines and the durability of the immune response are the focus of ongoing clinical trials. Conjugate and polysaccharide pneumococcal vaccines have similar efficacy against invasive pneumococcal disease and pneumococcal pneumonia caused by vaccine serotypes in older adults. Their relative value varies by setting, depending on the prevalence of vaccine serotypes, largely related to conjugate vaccine coverage in children. Improved efficacy will increase public confidence and uptake of these vaccines. Co-administration of these vaccines is feasible and important for maximal uptake in older people. Development of new vaccine platforms has accelerated following the arrival of SARS-CoV-2, and will likely result in new vaccines against other pathogens in the future.

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“…Following Huddelston et.al. (Huddleston et al, 2020) with the mutation rate per position per generation set to 2.04E-6 (yearly substitution rate/(generations in one year * genome size)). The transition bias was set to 3.0 for baseline simulations.…”

Section: Santa-sim Simulationsmentioning

confidence: 99%

The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA supertype-dependent manner

Hamelin

Fournelle

Grenier

et al. 2021

Preprint

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The rapid, global dispersion of SARS-CoV-2 since its initial identification in December 2019 has led to the emergence of a diverse range of variants. The initial concerns regarding the virus were quickly compounded with concerns relating to the impact of its mutated forms on viral infectivity, pathogenicity and immunogenicity. To address the latter, we seek to understand how the mutational landscape of SARS-CoV-2 has shaped HLA-restricted T cell immunity at the population level during the first year of the pandemic, before mass vaccination. We analyzed a total of 330,246 high quality SARS-CoV-2 genome assemblies sampled across 143 countries and all major continents. Strikingly, we found that specific mutational patterns in SARS-CoV-2 diversify T cell epitopes in an HLA supertype-dependent manner. In fact, we observed that proline residues are preferentially removed from the proteome of prevalent mutants, leading to a predicted global loss of SARS-CoV-2 T cell epitopes in individuals expressing HLA-B alleles of the B7 supertype family. In addition, we show that this predicted global loss of epitopes is largely driven by a dominant C-to-U mutation type at the RNA level. These results indicate that B7 supertype-associated epitopes, including the most immunodominant ones, were more likely to escape CD8+ T cell immunosurveillance during the first year of the pandemic. Together, our study lays the foundation to help understand how SARS-CoV-2 mutants shape the repertoire of T cell targets and T cell immunity across human populations. The proposed theoretical framework has implications in viral evolution, disease severity, vaccine resistance and herd immunity.

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Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution

Cited by 61 publications

References 48 publications

Limited Predictability of Amino Acid Substitutions in Seasonal Influenza Viruses

Limited Predictability of Amino Acid Substitutions in Seasonal Influenza Viruses

Vaccines for older adults

The mutational landscape of SARS-CoV-2 variants diversifies T cell targets in an HLA supertype-dependent manner

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