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: 9.81). 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.

Download full-text


Available from: Jason A Greenbaum, Jul 06, 2015
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    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
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Here we analyzed the molecular targets associated with myasthenia gravis (MG) immune responses, enabled by an immune epitope database (IEDB) inventory of approximately 600 MG-related epitopes derived from 175 references. The vast majority of epitopes were derived from the α-subunit of human AChR suggesting that other MG-associated autoantigens should be investigated further. Human α-AChR was mostly characterized in humans, whereas reactivity primarily to T. californica AChR was examined in animal models. While the fine specificity of T-cell response was similar in the two systems, substantial antibody reactivity to the C-terminus was detected in the nonhuman system, but not in humans. Further analysis showed that the reactivity of nonhuman hosts to the C-terminus was eliminated when data were restricted to hosts tested in the context of autoimmune disease (spontaneous or induced), demonstrating that the epitopes recognized in humans and animals were shared when disease was present. Finally, we provided data subsets relevant to particular applications, including those associated with HLA typing or restriction, sets of epitopes recognized by monoclonal antibodies, and epitopes associated with modulation of immunity or disease. In conclusion, this analysis highlights gaps, differences, and similarities in the epitope repertoires of humans and animal models.
    12/2012; 2012:403915. DOI:10.1155/2012/403915
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The novel strain H1N1 caused the outbreak of first pandemic influenza in 21 century. Now it is a common component of current seasonal in-fluenza viruses. The recent transmission and plentiful genome sequences available provided a good opportunity to study the origin and evo-lution of epitopes on the proteins of human in-fluenza virus. In the present study, the B-cell epitope compositions in the pandemic strains, circulat-ing traditional seasonal strains, swine strains as well as highly virulent avian strain H5N1 were identified with the aid of the Immune Epitope DataBase (IEDB) and were compared at genomic level. A total of 14210 distinct sequen-ces down-loaded from NCBI database were used for analysis. Some epitopes on proteins HA or NA, not conserved in recent seasonal strains, were found in 2009 pandemic strains but existed in the early human strains (1919-1935). The pan-demic strain shared higher conserved epitopes with "bird flu" virus H5N1than classic human seasonal strains. The epitopes that could exist at common antigenic regions of HA protein are needed to further identify. The genetic exchan-ges between human and swine population by transmission was very active but the princepal side of the transmission could be from swine to human. These results provided valuable infor-mation on influenza A virus evolution and transmission by means of epitope analysis at genomic level.
    Health 10/2012; 04(10-4):946-954430145. DOI:10.4236/health.2012.430145 · 0.51 Impact Factor