Coupling sensitivein vitroandin silicotechniques to assess cross-reactive CD4+T cells against the swine-origin H1N1 influenza virus

• Published in: Vaccine Vol. 29; no. 17; p. 3299
• Main Authors: Schanen, Brian C, De Groot, Anne S, Moise, L, Ardito, Matt, McClaine, Elizabeth, Martin, William, Wittman, Vaughan, Warren, William L, Drake, Donald R
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Limited 12.04.2011
• Subjects: Bioassays; Laboratory animals; Lymphocytes; Peptides; Proteins; Studies; Swine flu; Vaccines; Viruses
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2011.02.019

The outbreak of the novel swine-origin H1N1 influenza in the spring of 2009 took epidemiologists, immunologists, and vaccinologists by surprise and galvanized a massive worldwide effort to produce millions of vaccine doses to protect against this single virus strain. Of particular concern was the apparent lack of pre-existing antibody capable of eliciting cross-protective immunity against this novel virus, which fueled fears this strain would trigger a particularly far-reaching and lethal pandemic. Given that disease caused by the swine-origin virus was far less severe than expected, we hypothesized cellular immunity to cross-conserved T cell epitopes might have played a significant role in protecting against the pandemic H1N1 in the absence of cross-reactive humoral immunity. In a published study, we used an immunoinformatics approach to predict a number of CD4+T cell epitopes are conserved between the 2008-2009 seasonal H1N1 vaccine strain and pandemic H1N1 (A/California/04/2009) hemagglutinin proteins. Here, we provide results from biological studies using PBMCs from human donors not exposed to the pandemic virus to demonstrate that pre-existing CD4+T cells can elicit cross-reactive effector responses against the pandemic H1N1 virus. As well, we show our computational tools were 80-90% accurate in predicting CD4+T cell epitopes and their HLA-DRB1-dependent response profiles in donors that were chosen at random for HLA haplotype. Combined, these results confirm the power of coupling immunoinformatics to define broadly reactive CD4+T cell epitopes with highly sensitivein vitrobiological assays to verify thesein silicopredictions as a means to understand human cellular immunity, including cross-protective responses, and to define CD4+T cell epitopes for potential vaccination efforts against future influenza viruses and other pathogens.