Intranasal vaccination with engineered BCG expressing CCL2 induces a stronger immune barrier against Mycobacterium tuberculosis than BCG.

Intradermal Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccination is currently the only licensed strategy for preventing tuberculosis (TB). It provides limited protection against pulmonary TB. To enhance the efficacy of BCG, we developed a recombinant BCG expressing exogenous monocyte chemoattractant CC chemokine ligand 2 (CCL2), termed rBCG-CCL2. Co-culturing macrophages with rBCG-CCL2 enhances their abilities in migration, phagocytosis, and effector molecules expression. In the mouse model, intranasal vaccination with rBCG-CCL2 induced greater immune cells infiltration and a more extensive innate immune responses in lung compared to vaccination with parental BCG, as determined by multiparameter flow cytometry, transcriptomic analysis, and pathological assessments. Moreover, rBCG-CCL2 induced a high frequency of activated macrophages and antigen-specific Th1 and Th17 T cells in lungs. The enhanced immune microenvironment responded more effectively to intravenous challenge with Mycobacterium tuberculosis (Mtb) H37Ra, leading to significant reductions in H37Ra burden and pathological damage to the lungs and spleen. Intranasal rBCG-CCL2 vaccinated mice rapidly initiated pro-inflammatory Th1 cytokine release and reduced pathological damage to the lungs and spleen during the early stage of H37Ra challenge. The finding that co-expression of CCL2 synergistically enhances the immune barrier induced by BCG provides a model for defining immune correlates and mechanisms of vaccine-elicited protection against TB.

Water bath is more efficient than hot air oven at thermal inactivation of coronavirus.

BACKGROUND: Thermal inactivation is a conventional and effective method of eliminating the infectivity of pathogens from specimens in clinical and biological laboratories, and reducing the risk of occupational exposure and environmental contamination. During the COVID-19 pandemic, specimens from patients and potentially infected individuals were heat treated and processed under BSL-2 conditions in a safe, cost-effective, and timely manner. The temperature and duration of heat treatment are optimized and standardized in the protocol according to the susceptibility of the pathogen and the impact on the integrity of the specimens, but the heating device is often undefined. Devices and medium transferring the thermal energy vary in heating rate, specific heat capacity, and conductivity, resulting in variations in efficiency and inactivation outcome that may compromise biosafety and downstream biological assays. METHODS: We evaluated the water bath and hot air oven in terms of pathogen inactivation efficiency, which are the most commonly used inactivation devices in hospitals and biological laboratories. By evaluating the temperature equilibrium and viral titer elimination under various conditions, we studied the devices and their inactivation outcomes under identical treatment protocol, and to analyzed the factors, such as energy conductivity, specific heat capacity, and heating rate, underlying the inactivation efficiencies. RESULTS: We compared thermal inactivation of coronavirus using different devices, and have found that the water bath was more efficient at reducing infectivity, with higher heat transfer and thermal equilibration than a forced hot air oven. In addition to the efficiency, the water bath showed relative consistency in temperature equilibration of samples of different volumes, reduced the need for prolonged heating, and eliminated the risk of pathogen spread by forced airflow. CONCLUSIONS: Our data support the proposal to define the heating device in the thermal inactivation protocol and in the specimen management policy.

Surveillance of common respiratory infections during the COVID-19 pandemic demonstrates the preventive efficacy of non-pharmaceutical interventions.

OBJECTIVE: The emergence of a novel coronavirus, SARS-CoV-2, and its subsequent spread outside of Wuhan, China, led to the human society experiencing a pandemic of coronavirus disease 2019 (COVID-19). While the development of vaccines and pharmaceutical treatments are ongoing, government authorities in China have implemented unprecedented non-pharmaceutical interventions as primary barriers to curb the spread of the deadly SARS-CoV-2 virus. Although the decline of COVID-19 cases coincided with the implementation of such interventions, we searched for evidence to demonstrate the efficacy of these interventions, since artifactual factors, such as the environment, the pathogen itself, and the phases of epidemic, may also alter the patterns of case development. METHODS: We surveyed common viral respiratory infections that have a similar pattern of transmission, tropism, and clinical manifestation, as COVID-19 under a series of non-pharmaceutical interventions during the current pandemic season. We then compared this data with historical data from previous seasons without such interventions. RESULTS: Our survey showed that the rates of common respiratory infections, such as influenza and respiratory syncytial virus infections, decreased dramatically from 13.7% (95% CI, 10.82-16.58) and 4.64% (95% CI, 2.88-7.64) in previous years to 0.73% (95% CI, 0.02-1.44) and 0.0%, respectively, in the current season. CONCLUSIONS: Our surveillance provides compelling evidence that non-pharmaceutical interventions are cost-effective ways to curb the spread of contagious agents, and may represent the only practical approach to limit the evolving epidemic until specific vaccines and pharmaceutical treatments are available.