Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human population

Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 11/2009; 106(48):20365-70. DOI: 10.1073/pnas.0911580106
Source: PubMed

ABSTRACT A major concern about the ongoing swine-origin H1N1 influenza virus (S-OIV) outbreak is that the virus may be so different from seasonal H1N1 that little immune protection exists in the human population. In this study, we examined the molecular basis for pre-existing immunity against S-OIV, namely the recognition of viral immune epitopes by T cells or B cells/antibodies that have been previously primed by circulating influenza strains. Using data from the Immune Epitope Database, we found that only 31% (8/26) of B-cell epitopes present in recently circulating H1N1 strains are conserved in the S-OIV, with only 17% (1/6) conserved in the hemagglutinin (HA) and neuraminidase (NA) surface proteins. In contrast, 69% (54/78) of the epitopes recognized by CD8(+) T cells are completely invariant. We further demonstrate experimentally that some memory T-cell immunity against S-OIV is present in the adult population and that such memory is of similar magnitude as the pre-existing memory against seasonal H1N1 influenza. Because protection from infection is antibody mediated, a new vaccine based on the specific S-OIV HA and NA proteins is likely to be required to prevent infection. However, T cells are known to blunt disease severity. Therefore, the conservation of a large fraction of T-cell epitopes suggests that the severity of an S-OIV infection, as far as it is determined by susceptibility of the virus to immune attack, would not differ much from that of seasonal flu. These results are consistent with reports about disease incidence, severity, and mortality rates associated with human S-OIV.

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    • "In April 2009, an acute febrile respiratory illness that spread rapidly across Mexico and the United States [1], was reported. This aetiological pathogenic virus was later identified as a new influenza A strain (referred to as A(H1N1)pdm09 virus in this article), a re-assorted variant of North American and Eurasian swine lineages which was immunologically distinct from the circulating seasonal influenza A strain H1N1s [2]. The geographic dispersion of this virus resulted in high numbers of new cases that overwhelmed laboratories and the clinical capacity of many nations, compelling the WHO to issue a pandemic alert on June, 11th 2009 [1]. "
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    ABSTRACT: Following the 2009 swine flu pandemic, a cohort for pandemic influenza (CoPanFlu) study was established in Djibouti, the Horn of Africa, to investigate its case prevalence and risk predictors' at household level. From the four city administrative districts, 1,045 subjects from 324 households were included during a face-to-face encounter between 11th November 2010 and 15th February 2011. Socio-demographic details were collected and blood samples were analysed in haemagglutination inhibition (HI) assays. Risk assessments were performed in a generalised estimating equation model. In this study, the indicator of positive infection status was set at an HI titre of >= 80, which was a relevant surrogate to the seroconversion criterion. All positive cases were considered to be either recent infections or past contact with an antigenically closely related virus in humans older than 65 years. An overall sero-prevalence of 29.1% and a geometrical mean titre (GMT) of 39.5% among the residents was observed. Youths, <= 25 years and the elderly, >=65 years had the highest titres, with values of 35.9% and 29.5%, respectively. Significantly, risk was high amongst youths <= 25 years, (OR 1.5-2.2), residents of District 4(OR 2.9), students (OR 1.4) and individuals living near to river banks (OR 2.5). Belonging to a large household (OR 0.6), being employed (OR 0.5) and working in open space-outdoor (OR 0.4) were significantly protective. Only 1.4% of the cohort had vaccination against the pandemic virus and none were immunised against seasonal influenza. Despite the limited number of incident cases detected by the surveillance system, A(H1N1)pdm09 virus circulated broadly in Djibouti in 2010 and 2011. Age-group distribution of cases was similar to what has been reported elsewhere, with youths at the greatest risk of infection. Future respiratory infection control should therefore be tailored to reach specific and vulnerable individuals such as students and those working in groups indoors. It is concluded that the lack of robust data provided by surveillance systems in southern countries could be responsible for the underestimation of the epidemiological burden, although the main characteristics are essentially similar to what has been observed in developed countries.
    Virology Journal 01/2014; 11(1):13. DOI:10.1186/1743-422X-11-13 · 2.18 Impact Factor
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    • "In that scenario, the role of isolation, quarantine and other non-pharmaceutical interventions stimulated by media coverage becomes more significant as disease control strategies. Despite initial concern that little protective immunity existed in the general population for pandemic H1N1 (2009), subsequent epidemiological data showed that morbidity in the elderly was lower than that in younger individuals, suggesting the existence of pre-existing immunity [16] [19] [27] [58]. The Centers for Disease Control and Prevention (Atlanta, GA, USA) reported that among persons > 60 years old, 33% have pre-existing, cross-reactive neutralizing antibodies against the new virus of pandemic (H1N1) 2009 [58]. "
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    ABSTRACT: An autonomous deterministic non-linear epidemic model SEQIHRS is proposed for the transmission dynamics of an infectious disease with quarantine and isolation control strategies in a community with pre-existing immunity. The model exhibits two equilibria, namely, the disease-free and a unique endemic equilibrium. The existence and local stability of the disease free and endemic equilibria are explored in terms of the effective reproduction number ℛ C . It is observed that media coverage does not affect the effective reproduction number, but it helps to mitigate disease burden by lowering the number of infectious individuals at the endemic steady state and also lowering the infection peak. A new approach is proposed to estimate the coefficient of media coverage. Using the results of central manifold theory, it is established that as ℛ C passes through unity, transcritical bifurcation occurs in the system and the unique endemic equilibrium is asymptotically stable. It is observed that the population level impact of quarantine and isolation depend on the level of transmission by the isolated individuals. Moreover, the higher level of pre-existing immunity in the population decreases the infection peak and causes its early arrival. Theoretical findings are supported by numerical simulation. Sensitivity analysis is performed for ℛ C and state variables at endemic steady state with respect to model parameters.
    Journal of Mathematical Analysis and Applications 01/2014; DOI:10.1016/j.jmaa.2014.08.019 · 1.12 Impact Factor
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    • "The structural analysis of H1N1 protein surfaces using homology modeling is challenged by the limited structural template coverage of some influenza proteins. Three-dimensional structures of several influenza A proteins have been modeled before and used for functional and evolutionary studies [48–52]. Unfortunately, for some influenza proteins (M2, NS2, PB1, PB2) the templates cover only a small portion of the target sequence, while for other influenza proteins the entire sequence is covered by a single template or a number of templates with a little or no structural overlap (HA, M1, NA, NP, NS1, PA). "
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    PLoS ONE 11/2013; 8(11):e81027. DOI:10.1371/journal.pone.0081027 · 3.23 Impact Factor
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