Immunogenicity consistency and safety with different production scales of recombinant adenovirus type-5 vectored COVID-19 vaccine in healthy adults: a randomized, double-blinded, immunobridging trial.

BACKGROUND: The certification of immunogenicity consistency at different production scales is indispensable for the quality control of vaccines. RESEARCH DESIGN AND METHODS: A randomized, double-blind immunobridging trial in healthy adults aged 18-59 was divided into Scale A (50 L and 800 L) and Scale B (50 L and 500 L) based on vaccine manufacturing scales. Eligible participants in Scale A were randomly assigned to receive the single-dose recombinant adenovirus type-5 vectored COVID-19 vaccine (Ad5-nCoV) of different scales at a 1:1 ratio, as was Scale B. The primary endpoint was the geometric mean titer (GMT) of anti-live SARS-CoV-2-specific neutralizing antibodies (NAb) 28 days post-vaccination. RESULTS: 1,012 participants were enrolled, with 253 (25%) per group. The post-vaccination GMTs of NAb were 10.72 (95% CI: 9.43, 12.19) and 13.23 (11.64, 15.03) in Scale A 50 L and 800 L, respectively; 11.64 (10.12, 13.39) and 12.09 (10.48, 13.95) in Scale B 50 L and 500 L, respectively. GMT ratios in Scale A and B have a 95% CI of 0.67-1.5. Most adverse reactions were mild or moderate. 17 of 18 participants reported non-vaccination-related serious adverse reactions. CONCLUSIONS: The Ad5-nCoV in the scale-up production of 500 L and 800 L showed consistent immunogenicity with the original 50 L production scale, respectively.

Repulsive synchronization in complex networks.

Synchronization in complex networks characterizes what happens when an ensemble of oscillators in a complex autonomous system become phase-locked. We study the Kuramoto model with a tunable phase-lag parameter α in the coupling term to determine how phase shifts influence the synchronization transition. The simulation results show that the phase frustration parameter leads to desynchronization. We find two global synchronization regions for α∈[0,2π) when the coupling is sufficiently large and detect a relatively rare network synchronization pattern in the frustration parameter near α=π. We call this frequency-locking configuration as "repulsive synchronization," because it is induced by repulsive coupling. Since the repulsive synchronization cannot be described by the usual order parameter r, the parameter frequency dispersion is introduced to detect synchronization.

Correction: Advanced Algorithms for Local Routing Strategy on Complex Networks.

[This corrects the article DOI: 10.1371/journal.pone.0156756.].