The significant number of people with latent and active tuberculosis infection requires further efforts to develop new vaccines or improve the Bacillus Calmette-Guérin (BCG), which is the only approved vaccine against this disease. In this study, we developed a recombinant fusion protein (PEPf) containing high-density immunodominant epitope sequences from Rv0125, Rv2467, and Rv2672 Mycobacterium tuberculosis (Mtb) proteases that proved immunogenic and used it to develop a recombinant BCG vaccine expressing the fusion protein. After challenging using Mtb, a specific immune response was recalled, resulting in a reduced lung bacterial load with similar protective capabilities to BCG. Thus BCG PEPf failed to increase the protection conferred by BCG. The PEPf was combined with Advax4 adjuvant and tested as a subunit vaccine using a prime-boost strategy. PEPf + Advax4 significantly improved protection after Mtb challenge, with a reduction in bacterial load in the lungs. Our results confirm that Mtb proteases can be used to develop vaccines against tuberculosis and that the use of the recombinant PEPf subunit protein following a prime-boost regimen is a promising strategy to improve BCG immunity.
Quadrature phase-shift keying (QPSK) and 16-quadrature amplitude modulation (16QAM) formats are deployed in inter-data center networks where high transmission capacity and spectral efficiency are required. However, in intra-data center networks, a four-level pulse amplitude modulation (PAM4) format is deployed to satisfy the requirements for a simple and low-cost transceiver configuration. For the seamless and effective connection of such heterogeneous networks without an optical-electricaloptical conversion, an all-optical modulation format conversion technique is required. In this paper, we propose all-optical PAM4 to QPSK and 16QAM modulation format conversions using silicon-rich nitride waveguides. The successful conversions from 50-Gbps-class PAM4 signals to 50-Gbps-class QPSK and 100-Gbps-class 16QAM signals are demonstrated via numerical simulations.
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