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Open Access Research article

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

Venkata R Duvvuri13*, Bhargavi Duvvuri2, Veronica Jamnik2, Jonathan B Gubbay4567, Jianhong Wu3 and Gillian E Wu12

Author Affiliations

1 Biology Department, York University, Toronto, Canada

2 Kinesiology & Health Science, York University, Toronto, Canada

3 Centre for Disease Modeling, York Institute of Health Research, Toronto, Canada

4 Ontario Agency for Health Protection and Promotion, Toronto, Canada

5 Mount Sinai Hospital, Toronto, Canada

6 University of Toronto, Toronto, Canada

7 The Hospital for Sick Children, Toronto, Canada

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BMC Infectious Diseases 2013, 13:204  doi:10.1186/1471-2334-13-204

Published: 4 May 2013

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-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.

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