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T cell memory to evolutionarily conserved and shared hemagglutinin epitopes of H1N1 viruses: a pilot scale study

tetano

Editor, Senior Moderator
BMC Infect Dis. 2013 May 4;13(1):204. [Epub ahead of print]
T cell memory to evolutionarily conserved and shared hemagglutinin epitopes of H1N1 viruses: a pilot scale study.
Duvvuri VR, Duvvuri B, Jamnik V, Gubbay JB, Wu J, Wu GE.
Abstract
BACKGROUND:

The 2009 pandemic influenza was milder than expected. Based on the apparent lack of pre-existing cross-protective antibodies to the A (H1N1)pdm09 strain, it was hypothesized that pre-existing CD4+ T cellular immunity provided the crucial immunity that led to an attenuation of disease severity. We carried out a pilot scale study by conducting in silico and in vitro T cellular assays in healthy population, to evaluate the pre-existing immunity to A (H1N1)pdm09 strain.
METHODS:

Large-scale epitope prediction analysis was done by examining the NCBI available (H1N1) HA proteins. NetMHCIIpan, an eptiope prediction tool was used to identify the putative and shared CD4+ T cell epitopes between seasonal H1N1 and A (H1N1)pdm09 strains. To identify the immunogenicity of these putative epitopes, human IFN-gamma-ELISPOT assays were conducted using the peripheral blood mononuclear cells from fourteen healthy human donors. All donors were screened for the HLA-DRB1 alleles.
RESULTS:

Epitope-specific CD4+ T cellular memory responses (IFN-gamma) were generated to highly conserved HA epitopes from majority of the donors (93%). Higher magnitude of the CD4+ T cell responses was observed in the older adults. The study identified two HA2 immunodominant CD4+ T cell epitopes, of which one was found to be novel.
CONCLUSIONS:

The current study provides a compelling evidence of HA epitope specific CD4+ T cellular memory towards A (H1N1)pdm09 strain. These well-characterized epitopes could recruit alternative immunological pathways to overcome the challenge of annual seasonal flu vaccine escape.

PMID:
23641949
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/23641949
 
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