Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus

Xu, Rui; Ekiert, D.C.; Krause, Jens C.; Hai, Rong; Crowe, James E.; Wilson, Ian A.

doi:10.1126/science.1186430

Cited by 524 publications

(608 citation statements)

References 27 publications

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“…Potential H1pdm/09-related induction of broadly cross-reactive antibodies [10] is therefore unlikely to have skewed our results. Yet, our data are consistent with findings that H1pdm/ 09 possesses an epitope that is shared with the H1N1 virus strains circulating before 1957; individuals born before 1957 had higher titers to H1pdm/09 than younger participants [11,12]. Although the binding titers were expected to increase with age in the nonvaccinated cohort, no peak in elderly persons appeared in nonparametric smoothing.…”

Section: Discussionsupporting

confidence: 91%

Prevalence and Predictors for Homo- and Heterosubtypic Antibodies Against Influenza A Virus

Kohler¹,

Scherrer²,

Zagordi³

et al. 2014

Clinical Infectious Diseases

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Background. The effectiveness of trivalent influenza vaccination has been confirmed in several studies. To date, it is not known whether repeated exposure and vaccination to influenza promote production of cross-reactive antibodies. Furthermore, how strains encountered earlier in life imprint the immune response is currently poorly understood.Methods. To determine the prevalence for human homo-and heterosubtypic antibody responses, we scrutinized serum samples from 305 healthy volunteers for hemagglutinin-binding and -neutralizing antibodies against several strains and subtypes of influenza A. Statistical analyses were then performed to establish the association of measured values with potential predictors.Results. It was found that vaccination not only promoted higher binding and neutralizing antibody titers to homosubtypic influenza isolates but also increased heterosubtypic human immune responses. Both binding and neutralizing antibody titers in relation with age of the donors mirrored the course of the different influenza strain circulation during the last century. Advanced age appeared to be of advantage for both binding and neutralizing titers to most subtypes. In contrast, the first virus subtype encountered was found to imprint to some degree subsequent antibody responses. Antibodies to recent strains, however, primarily seemed to be promoted by vaccination.Conclusions. We provide evidence that vaccinations stimulate both homo-and heterosubtypic immune responses in young and middle-aged as well as more senior individuals. Our analyses suggest that influenza vaccinations not only prevent infection against currently circulating strains but can also stimulate broader humoral immune responses that potentially attenuate infections with zoonotic or antigenically shifted strains.

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Section: Discussionsupporting

confidence: 91%

Prevalence and Predictors for Homo- and Heterosubtypic Antibodies Against Influenza A Virus

Kohler¹,

Scherrer²,

Zagordi³

et al. 2014

Clinical Infectious Diseases

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“…Conversely, pre‐pandemic seroprevalence and GMT increased with age and was highest in the oldest age‐group which was protected from infection, apparently due to their exposure to the 1918 H1N1 pandemic virus 15, 16, 17…”

Section: Discussionmentioning

confidence: 99%

The dynamics of infection and the persistence of immunity to A(H1N1)pdm09 virus in Israel

Weil

Shohat

Bromberg

et al. 2012

Influenza Resp Viruses

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BackgroundInfluenza virus A(H1N1)pdm09 first appeared in Israel in late April 2009, disappeared in mid‐March 2010, and reappeared in late October 2010. Symptoms were mostly mild without need for medical care.ObjectivesTo provide targets for future pandemic preparedness and response by evaluating the dynamics and cumulative incidence of A(H1N1)pdm09 infection, the virus‐specific seroprevalence (HI antibody titer >1:40) at the height of the pandemic, during its decline and thereafter.MethodsA cross‐sectional seroepidemiological study was conducted on 6911 serum samples collected before, during, and after the pandemic.ResultsCumulative incidence of infection derived from the differences between post‐ and pre‐pandemic seroprevalence was 54·1%, 32·9%, 22·9%, 14·8%, and 6·3% in age‐groups 0–9, 10–19, 20–49, 50–79, and ≥80 years, respectively, and 28·5% for all age‐groups combined. Vaccination could have contributed at the most 4·6% to the post‐pandemic population seroprevalence. High pre‐pandemic immune response (47·4%) found in a cohort aged 15–18 year was strongly associated with birth years 1990–1993. Morbidity began to decline in mid‐November 2009 at 32·8% population seroprevalence (45% in ages 0–19 year) and stopped in March 2010 at 43·4% population seroprevalence in February 2010 (70% in ages 0–19 year). Between February and September 2010, seroprevalence declined by 12·2% allowing virus recirculation from October 2010.ConclusionsOur study provides targets for controlling future influenza pandemics in Israel. Vaccination should focus on the younger age‐groups (0–19 year) which played a key role in transmission of the A(H1N1)pdm09 due to lack of background immunity (ages 0–9 year) and high exposure rates (ages 10–19 year).

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“…In Figure 3, we superimpose our model with the complex of the antigenically similar HA of the 1918 influenza A(H1) virus bound to an antibody that recognises the classical Sa epitope (PDB:3LZF) [5]. We show that N142D is centrally located in this epitope, which led us to further investigate the effect of the mutation on antigenic properties with haemagglutination inhibition assays.…”

Section: Genetic Characterisation Of the Pandemic Influenza A(h1n1) Vmentioning

confidence: 98%

“…To further investigate the importance of these surface antigen mutations, we built a structural homology model of HA from the A/Brisbane/10/2010(H1N1) virus based on the template structure of A/ California/04/2009(H1N1) (PDB:3LZG) [5] using MODELLER with loop refinement [6] and ProQ [7] for model quality control. In Figure 3, we superimpose our model with the complex of the antigenically similar HA of the 1918 influenza A(H1) virus bound to an antibody that recognises the classical Sa epitope (PDB:3LZF) [5].…”

Section: Genetic Characterisation Of the Pandemic Influenza A(h1n1) Vmentioning

confidence: 99%

A new pandemic influenza A(H1N1) genetic variant predominated in the winter 2010 influenza season in Australia, New Zealand and Singapore

et al. 2010

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Pandemic H1N1 influenza virus is of global health concern and is currently the predominant influenza virus subtype circulating in the southern hemisphere 2010 winter. The virus has changed little since it emerged in 2009, however, in this report we describe several genetically distinct changes in the pandemic H1N1 influenza virus. These variants were first detected in Singapore in early 2010 and have subsequently spread through Australia and New Zealand. At this stage, these signature changes in the haemagglutinin and neuraminidase proteins have not resulted in significant antigenic changes which might make the current vaccine less effective, but such adaptive mutations should be carefully monitored as the northern hemisphere approaches its winter influenza season.

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Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus

Abstract: The 2009 H1N1 swine flu

Cited by 524 publications

References 27 publications

Prevalence and Predictors for Homo- and Heterosubtypic Antibodies Against Influenza A Virus

Prevalence and Predictors for Homo- and Heterosubtypic Antibodies Against Influenza A Virus

The dynamics of infection and the persistence of immunity to A(H1N1)pdm09 virus in Israel

A new pandemic influenza A(H1N1) genetic variant predominated in the winter 2010 influenza season in Australia, New Zealand and Singapore

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