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The respiratory syncytial virus (RSV) fusion (F) glycoprotein is highly immunogenic in its prefusion (pre-F) conformation. However, the protein is unstable, and its conformation must be stabilized for it to function effectively as an immunogen in vaccines. We present a mutagenesis strategy to arrest the RSV F protein in its pre-F state by blocking localized changes in protein structure that accompany large-scale conformational rearrangements. We generated a series of mutants and screened them in vitro to assess their potential for forming a stable pre-F. In animals, the immunogenicity of a representative mutant F protein, with a conformation confirmed by cryo-electron microscopy, elicited levels of neutralizing antibodies and protection against RSV-induced lung damage that were comparable to those of DS-Cav1, a pre-F used in a licensed vaccine.

Objective: To investigate the effects of novel BimunoGalactooligosaccharides (B-GOS) on cognitive behavior and depression of APP/PS1/tau Alzheimer's disease transgenic mice. Methods: Five-month-old male APP/PS1/tau AD transgenic mice and C57BL/6J control mice were divide into C57+Vehicle group, C57+B-GOS group, APP/PS1/tau+Vehicle group and APP/PS1/tau+B-GOS group, with 10 mice in each group. After continuous administration of B-GOS for 5 months, the cognitive behavior and depressive mood changes of mice in each group were detected by open field experiment, new object recognition experiment, Y maze experiment, Morris water maze experiment, tail suspension test, forced swimming test and conditioned fear experiment, respectively. Results: ①Open field experiment: the percentage of activity time in the central area of open field in APP/PS1/tau+Vehicle group mice was significantly lower than that in C57+Vehicle group mice ( P ＜0.01), and was remarkably increased after B-GOS intervention ( P ＜0.05). ② New object recognition experiment: the new object recognition index (NOI) of APP/PS1/tau+Vehicle group mice was significantly lower than that of C57+Vehicle group mice ( P ＜0.01), and was observably increased after B-GOS intervention ( P ＜0.05). ③ Y maze experiment: the spontaneous alternation correct rate of APP/PS1/tau+Vehicle group mice was notably lower than that in C57+Vehicle group ( P ＜0.01), and was distinctly increased after B-GOS intervention ( P ＜0.01). ④ Classical water maze experiment: the escape latency of APP/PS1/tau+Vehicle group mice on the 4th and 5th days was significantly longer than that of C57+Vehicle group mice ( P ＜0.01), which was markedly shortened after B-GOS intervention ( P ＜0.05). During the space exploration phase, the percentage of swimming time in the target quadrant and the times of crossing the platform in APP/PS1/tau+Vehicle group mice were significantly lower than those in C57+Vehicle group mice ( P ＜0.01), which were notably increased after B-GOS intervention ( P ＜0.01). ⑤ Tail suspension test and forced swimming test: the percentage of immobility time in APP/PS1/tau+Vehicle group mice was dramatically higher than that in C57+Vehicle group mice ( P ＜0.01), and was obviously reduced after B-GOS intervention ( P ＜ 0.01). ⑥ Conditioned fear experiment: before conditioned stimulus (CS), the freezing ratio of mice in each group had no statistical difference ( P ＞0.05). After CS, the freezing ratio of APP/PS1/tau+Vehicle group mice was significantly lower than that of C57+Vehicle group mice ( P ＜0.01), and was notably increased after B-GOS intervention ( P ＜0.01). Conclusion: B-GOS could reverse the cognitive behavioral impairment of APP/PS1/tau mice and alleviate their depression to a large extent.