Immune-engineered H7N9 influenza hemagglutinin improves protection against viral influenza virus challenge.
Immune-engineered H7N9 influenza hemagglutinin improves protection against viral influenza virus challenge.
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DOI：
10.1080/21645515.2020.1793711
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发表时间：
2020-09-01
影响因子：
4.8
通讯作者：
Ross TM
中科院分区：
文献类型：
--
作者：
Jang H;Meyers LM;Boyle C;De Groot AS;Moise L;Ross TM
从禽H7N9流感病毒株分离的流感血凝素（HA）引起弱免疫应答。这种低免疫原性可能是由于来自H7N9分离株A/Anhui/1/2013（Anh/13）的HA中的调节性T细胞（Treg）刺激表位。在本报告中，从野生型（WT）H7 HA氨基酸序列中去除该Treg刺激序列，并用来自人季节性H3 N2毒株的保守CD 4 + T细胞刺激序列替换，并设计OPT 1 H7 HA。使用表达人白细胞抗原（HLA）DR 3等位基因的人源化小鼠（HLA-DR 3）来确定这种优化的H7 HA蛋白的有效性。通过用H3 N2流感病毒A/Hong Kong/4108/2014感染来预免疫HLA-DR 3小鼠，然后用来自Anh/13的WT H7 HA或不含佐剂的OPT 1 H7 HA抗原肌内接种。OPT 1 H7 HA疫苗接种组引发更高的H7 HA特异性IgG滴度，导致与WT疫苗接种的小鼠相比，在用H7N9 Anh/13流感病毒致死性攻击后死亡率、体重减轻和肺病毒滴度更低。总的来说，T细胞表位工程化疫苗可以改善H7 HA抗原的免疫原性，从而提高针对H7N9流感病毒攻击的存活率和降低发病率。
The influenza hemagglutinin (HA) isolated from avian H7N9 influenza virus strains elicit weak immune responses. This low immunogenicity may be due to a regulatory T cell (Treg)–stimulating epitopes in HA from the H7N9 isolate A/Anhui/1/2013 (Anh/13). In this report, this Treg stimulating sequence was removed from the wild-type (WT) H7 HA amino acid sequence and replaced with a conserved CD4 + T cell stimulating sequences from human seasonal H3N2 strains and designed OPT1 H7 HA. The effectiveness of this optimized H7 HA protein was determined using a humanized mouse (HLA-DR3) expressing the human leukocyte antigen (HLA) DR3 allele. HLA-DR3 mice were pre-immunized by infecting with H3N2 influenza virus, A/Hong Kong/4108/2014 and then vaccinated intramuscularly with either the WT H7 HA from Anh/13 or the OPT1 H7 HA antigen without adjuvant. The OPT1 H7 HA vaccination group elicited higher H7 HA-specific IgG titers that resulted in a lower mortality, weight loss, and lung viral titer following lethal challenge with the H7N9 Anh/13 influenza virus compared to WT-vaccinated mice. Overall, T-cell epitope-engineered vaccines can improve the immunogenicity of H7 HA antigens resulting in enhanced survival and lower morbidity against H7N9 influenza virus challenge.