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

BMC Infectious Diseases

Gillian E Wu²  Jianhong Wu³  Jonathan B Gubbay¹  Veronica Jamnik²  Bhargavi Duvvuri²  Venkata R Duvvuri³ 

[1] The Hospital for Sick Children, Toronto, Canada;Kinesiology & Health Science, York University, Toronto, Canada;Centre for Disease Modeling, York Institute of Health Research, Toronto, Canada

关键词: Novel conserved HA epitope;    Immunodominant epitope;    CD4+ T cell epitope;    Hemagglutinin;    Influenza A/H1N1 viruses;   

Others  :  1148610
DOI  :  10.1186/1471-2334-13-204

 received in 2012-11-19, accepted in 2013-05-01,  发布年份 2013

【 摘 要 】

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-γ-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-γ) 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.

【 授权许可】

   
2013 Duvvuri et al.; licensee BioMed Central Ltd.

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