Immunoinformatic comparison of T-cell epitopes contained in novel swine-origin influenza A (H1N1) virus with epitopes in 2008-2009 conventional influenza vaccine.
In March 2009 a novel swine-origin influenza A (H1N1) virus (S-OIV) emerged in Mexico and the Western United States. Vaccination with conventional influenza vaccine (CIV) does not result in cross-reactive antibodies, however, the disproportionate number of cases (37%) occurring among persons younger than 50 years old suggested that adaptive immune memory might be responsible for the relative lack of virulence in older, healthy adults. Using EpiMatrix, a T-cell epitope prediction and comparison tool, we compared the sequences of the three hemagglutinin (HA) and neuraminidase (NA) proteins contained in 2008-2009 CIV to their counterparts in A/California/04/2009 (H1N1) looking for cross-conserved T-cell epitope sequences. We found greater than 50% conservation of T helper and CTL epitopes between novel S-OIV and CIV HA for selected HLA. Conservation was lower among NA epitopes. Sixteen promiscuous helper T-cell epitopes are contained in the S-OIV H1N1 HA sequence, of which nine (56%) were 100% conserved in the 2008-2009 influenza vaccine strain; 81% were either identical or had one conservative amino acid substitution. Fifty percent of predicted CTL epitopes found in S-OIV H1N1 HA were also found in CIV HA sequences. Based on historical performance, we expect these epitope predictions to be 93-99% accurate. This in silico analysis supports the proposition that T-cell response to cross-reactive T-cell epitopes, due to vaccination or exposure, may have the capacity to attenuate the course of S-OIV H1N1 induced disease-in the absence of cross-reactive antibody response. The value of the CIV or live-attenuated influenza vaccine containing the 2008-2009 vaccine strains, as defense against H1N1, could be further tested by evaluating human immune responses to the conserved T-cell epitopes using PBMC from individuals infected with H1N1 and from CIV vaccinees.
De Groot
Anne S
AS
EpiVax, 146 Clifford Street, Providence, RI 02903, USA. AnnieD@EpiVax.com
Ardito
Matt
M
McClaine
Elizabeth M
EM
Moise
Leonard
L
Martin
William D
WD
D000595:Amino Acid Sequence; D019295:Computational Biology; D017124:Conserved Sequence; D003429:Cross Reactions; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000276:immunology; D020539:Sequence Analysis, Protein
D018984:Epitopes, T-Lymphocyte; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D009439:Neuraminidase