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Induction of Cross-Reactive and Protective Antibody Responses After DNA Vaccination With MHCII-Targeted Stem Domain From Influenza Hemagglutinin.
Frontiers in Immunology ( IF 7.3 ) Pub Date : 2020-02-25 , DOI: 10.3389/fimmu.2020.00431
Gunnveig Grødeland 1 , Marta Baranowska-Hustad 1 , Justin Abadejos 2 , Tanya R Blane 2 , John Teijaro 2 , David Nemazee 2 , Bjarne Bogen 1
Affiliation  

Novel and more broadly protective vaccines against influenza are needed to efficiently meet antigenic drift and shift. Relevant to this end, the stem domain of hemagglutinin (HA) is highly conserved, and antibodies specific for epitopes located to the stem have been demonstrated to be able to confer broad protection against various influenza subtypes. However, a remaining challenge is to induce antibodies against the poorly immunogenic stem by vaccination strategies that can be scaled up for prophylactic vaccination of the general population. Here, we have developed DNA vaccines where the conserved stem domain of HA from influenza A/PR/8/34 (H1N1) and A/Shanghai/2/2013 (H7N9) was targeted toward MHC class II molecules on antigen-presenting cells (APC) for increased immunogenicity. Each of these vaccines induced antibodies that cross-reacted with other subtypes in the corresponding phylogenetic influenza groups. Importantly, when mixing the MHCII-targeted stem domains from H1N1 and H7N9 influenza viruses into one vaccine bolus, we observed broad protection against candidate stains from both phylogenetic groups 1 and 2.



中文翻译:

用来自流感血凝素的MHCII靶向的茎结构域进行DNA疫苗接种后,诱导交叉反应和保护性抗体应答。

为了有效地满足抗原的漂移和转移,需要新型的和更广泛的针对流感的保护性疫苗。与此相关,血凝素(HA)的茎结构域是高度保守的,并且已证明对位于茎的表位具有特异性的抗体能够针对各种流感亚型提供广泛的保护。然而,剩下的挑战是通过疫苗接种策略诱导针对免疫原性差的茎的抗体,该疫苗接种策略可以扩大用于普通人群的预防性疫苗接种。在这里,我们开发了DNA疫苗,其中A / PR / 8/34(H1N1)和A / Shanghai / 2/2013(H7N9)流感病毒的HA保守的茎结构域针对抗原呈递细胞上的MHC II类分子( APC)可提高免疫原性。这些疫苗中的每一种都诱导与相应系统发生性流感群中的其他亚型交叉反应的抗体。重要的是,当将来自H1N1和H7N9流感病毒的以MHCII为目标的茎结构域混合到一个疫苗中时,我们观察到了广泛的保护,可防止来自系统进化组1和2的候选染色。

更新日期:2020-03-30
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