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. 2009 Dec 1;106(48):20365-70.
doi: 10.1073/pnas.0911580106. Epub 2009 Nov 16.

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

Jason A Greenbaum  1 , Maya F Kotturi, Yohan Kim, Carla Oseroff, Kerrie Vaughan, Nima Salimi, Randi Vita, Julia Ponomarenko, Richard H Scheuermann, Alessandro Sette, Bjoern Peters
Affiliations

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

Jason A Greenbaum et al. Proc Natl Acad Sci U S A. .

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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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Location of the conserved epitope in the S-OIV HA protein structure. (A and B) Quaternary structure of the HA precursor (Protein Data Bank ID: 1HA0): frontal (A) and orthogonal (B) views. Monomer chains are in white, magenta, and green. Epitopes in each monomer are identical and shown in blue. (C and D) Quaternary structure of the cleaved HA modeled for the representative swine influenza HA sequence (ACP41934.1): frontal (C) and orthogonal (D) views. HA2 chains are in white, magenta, and green; corresponding HA1 chains are in cyan, orange, and red. Epitope is located at the N-terminal of HA2 chain and is identical in each chain.
Fig. 2.
Fig. 2.
Detection of pre-existing CD4+ and CD8+ T-cell immune responses to S-OIV. PBMC from normal individuals (n = 20) were stimulated with pools of either CD4+ or CD8+ T-cell epitopes from recent seasonal H1N1 influenza strains that were either absolutely conserved or not conserved in S-OIV sequences. Responses were measured through ex vivo IFN-γ ELISPOT assays. Error bars represent SEM.
Fig. 3.
Fig. 3.
S-OIV–specific CD4+ and CD8+ T cells appear to have an effector memory phenotype. PBMC from two representative normal donors were stimulated with either pools of (A) CD4+ or (B) CD8+ T-cell epitopes conserved in S-OIV sequences. The cells were gated for IFN-γ production and presence of the surface markers CD4 and CD8, respectively. Signal intensities of the gated cells for memory phenotypic markers CD45RA, CD62L, and CCR7 are shown.
Fig. 4.
Fig. 4.
Comparable pre-existing CD4+ and CD8+ T-cell immunity to S-OIV and 2008 seasonal influenza. PBMC from normal individuals (n = 20) were stimulated with pools of either CD4+ or CD8+ T-cell epitopes that were conserved in S-OIV or seasonal influenza 2008 sequences. Responses were measured through ex vivo IFN-γ ELISPOT assays. Error bars represent SEM.
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References

    1. Cohen J, Enserink M. Swine flu. After delays, WHO agrees: The 2009 pandemic has begun. Science. 2009;324:1496–1497. - PubMed
    1. Garten RJ, et al. Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science. 2009;325:197–201. - PMC - PubMed
    1. Itoh Y, et al. In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature. 2009 in press. - PMC - PubMed
    1. Centers for Disease Control and Prevention. Serum cross-reactive antibody response to a novel influenza A (H1N1) virus after vaccination with seasonal influenza vaccine. MMWR. 2009;58:521–524. - PubMed
    1. Munster VJ, et al. Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets. Science. 2009;325:481–483. - PMC - PubMed

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