Respiratory Syncytial Virus F And G Protein Core Fragments Fused To Hbsag-Binding Protein (Sbp) Induce A T(H)1-Dominant Immune Response Without Vaccine-Enhanced Disease

INTERNATIONAL IMMUNOLOGY(2019)

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摘要
The induction of a dominant T(h)2-type response is the main cause of harmful inflammation in respiratory syncytial virus (RSV) vaccine trials. A balanced T(h)1 versus T(h)2 immune response is needed for a safe and effective RSV vaccine. In this study, we evaluated the potential of a recombinant protein SBP-FG as a vaccine candidate with the main focus on shifting the harmful T(h)2 response to a T(h)1 response. SBP-FG consists of epitopes from RSV fusion (F) and attachment (G) proteins conjugated to the N-terminus of HBsAg-binding protein (SBP). SBP-FG induced significantly stronger immune responses assessed at the level of total IgG, IgA and neutralizing antibodies as compared with formalin-inactivated RSV (FI-RSV) and live RSV. Analysis of IgG isotypes, lung cytokines and T helper cells showed that SBP-FG induced a dominant T(h)1-type response. Further, SBP-FG immunized mice showed significantly reduced lung eosinophilia, reduced viral multiplication in lungs after challenge infection and provided protection against RSV infection. These results suggest that SBP-FG can be developed into a safe and effective vaccine against RSV. However, more studies are required to further evaluate SBP-FG as a potent vaccine candidate against RSV.An effective RSV vaccine that does not trigger lung inflammation
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关键词
eosinophilia, RSV vaccine, T(h)1 response, VED
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