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

[sharon sanders]

hat tip Fla Medic -

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

1. Jason A. Greenbaum^a,¹,
2. Maya F. Kotturi^a,¹,
3. Yohan Kim^a,
4. Carla Oseroff^a,
5. Kerrie Vaughan^a,
6. Nima Salimi^a,
7. Randi Vita^a,
8. Julia Ponomarenko^b,
9. Richard H. Scheuermann^c,
10. Alessandro Sette^a and
11. Bjoern Peters^a,²

+ Author Affiliations

1. <address>^aDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037; </address>
2. <address>^bSan Diego Supercomputer Center, University of California at San Diego, La Jolla, CA 92093; and </address>
3. <address>^cDepartment of Pathology and Division of Biomedical Informatics, University of Texas Southwestern Medical Center, Dallas, TX 75390 </address>

1. ↵¹J.A.G. and M.F.K. contributed equally to this work.
2. Communicated by Howard M. Grey, La Jolla Institute for Allergy and Immunology, La Jolla, CA, October 8, 2009 (received for review August 31, 2009)

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.



http://www.pnas.org/content/early/2009/11/13/0911580106.abstract

 

[Giuseppe]

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

Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human population (Proc Natl Acad Sci USA, abstract, edited)

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

1. Jason A. Greenbaum a,1, 2. Maya F. Kotturi a,1, 3. Yohan Kim a, 4. Carla Oseroff a, 5. Kerrie Vaughan a, 6. Nima Salimi a, 7. Randi Vita a, 8. Julia Ponomarenko b, 9. Richard H. Scheuermann c, 10. Alessandro Sette a and 11. Bjoern Peters a,2

- Author Affiliations
1. aDivision of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037;
2. bSan Diego Supercomputer Center, University of California at San Diego, La Jolla, CA 92093; and
3. cDepartment of Pathology and Division of Biomedical Informatics, University of Texas Southwestern Medical Center, Dallas, TX 75390

1. Communicated by Howard M. Grey, La Jolla Institute for Allergy and Immunology, La Jolla, CA, October 8, 2009
2. ↵1J.A.G. and M.F.K. contributed equally to this work. (received for review August 31, 2009)


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.

* databases
* epitopes
* meta-analysis
* pandemic


Footnotes

* 2To whom correspondence should be addressed. E-mail: bpeters@liai.org
* Author contributions: A.S. and B.P. designed research; J.A.G., M.F.K., and C.O. performed research; J.A.G., M.F.K., Y.K., K.V., N.S., R.V., J.P., R.H.S., A.S., and B.P. analyzed data; and J.A.G., M.F.K., J.P., R.H.S., A.S., and B.P. wrote the paper.
* The authors declare no conflict of interest.
* This article contains supporting information online at LINK.
-
​

<cite cite="http://www.pnas.org/content/106/48/20365.short?rss=1">Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human population ? PNAS</cite>

 

[gsgs]

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

Table 1. Number of influenza A H1N1
epitopes in the Immune Epitope Database

             recent
             seasonal
Epitope      H1N1      conserved
Category     epitopes  in newflu
---------------------------------
B-Cell          26        8 = 31%
T-cell,CD4+    139       57 = 41%
T-cell,CD8+     78       54 = 69%

medium number of preserved (known) epitopes
2000-2008: 16(B),66(T8),93(T4)
2009 : 8(B),54(T8),57(T4)




epitopes here:
http://www.pnas.org/content/suppl/2009/11/16/0911580106.DCSupplemental/0911580106SI.pdf

in .pdf rather than computer-readable but better than nothing



in HA:
GLFGAIAGF(B)
GLFGAIAGFI(T1)
TGMVDGWYGYHHQNEQGS(T2)
WTYNAELLVLLENERTLD(T2)
NKVNSVIEKMNTQFTAVG(T2)


******,230ff(4,H1): EIAIRPKVRDQEGRMNYYWTL