De Groot Anne S, Ardito Matt, McClaine Elizabeth M, Moise Leonard, Martin William D
EpiVax, 146 Clifford Street, Providence, RI 02903, USA.
Vaccine. 2009 Sep 25;27(42):5740-7. doi: 10.1016/j.vaccine.2009.07.040. Epub 2009 Aug 4.
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.
2009年3月，一种新型猪源甲型流感病毒（H1N1）（S-OIV）在墨西哥和美国西部出现。接种传统流感疫苗（CIV）不会产生交叉反应抗体，然而，50岁以下人群中出现的病例比例过高（37%）表明，适应性免疫记忆可能是导致健康老年人相对低毒力的原因。使用EpiMatrix（一种T细胞表位预测和比较工具），我们将2008 - 2009年CIV中包含的三种血凝素（HA）和神经氨酸酶（NA）蛋白序列与其在A/California/04/2009（H1N1）中的对应序列进行比较，寻找交叉保守的T细胞表位序列。我们发现，对于选定的HLA，新型S-OIV和CIV HA之间的T辅助细胞和CTL表位保守性超过50%。NA表位之间的保守性较低。S-OIV H1N1 HA序列中包含16个混杂的辅助性T细胞表位，其中9个（56%）在2008 - 2009年流感疫苗株中100%保守；81%要么相同，要么有一个保守的氨基酸替换。在S-OIV H1N1 HA中发现的预测CTL表位有50%也在CIV HA序列中发现。根据历史表现，我们预计这些表位预测的准确率为93 - 99%。这种计算机模拟分析支持了这样一种观点，即在没有交叉反应抗体反应的情况下，由于接种疫苗或接触而产生的针对交叉反应性T细胞表位的T细胞反应可能有能力减轻S-OIV H1N1诱导疾病的病程。通过使用来自感染H1N1的个体和CIV疫苗接种者的外周血单核细胞（PBMC）评估人类对保守T细胞表位的免疫反应，可以进一步测试CIV或含有2008 - 2009年疫苗株的减毒活流感疫苗作为预防H1N1的价值。
