Development of mRNA manufacturing for vaccines and therapeutics: mRNA platform requirements and development of a scalable production process to support early phase clinical trials.

The remarkable success of SARS CoV-2 mRNA-based vaccines and the ensuing interest in mRNA vaccines and therapeutics have highlighted the need for a scalable clinical-enabling manufacturing process to produce such products, and robust analytical methods to demonstrate safety, potency, and purity. To date, production processes have either not been disclosed or are bench-scale in nature and cannot be readily adapted to clinical and commercial scale production. To address these needs, we have advanced an aqueous-based scalable process that is readily adaptable to GMP-compliant manufacturing, and developed the required analytical methods for product characterization, quality control release, and stability testing. We also have demonstrated the products produced at manufacturing scale under such approaches display good potency and protection in relevant animal models with mRNA products encoding both vaccine immunogens and antibodies. Finally, we discuss continued challenges in raw material identification, sourcing and supply, and the cold chain requirements for mRNA therapeutic and vaccine products. While ultimate solutions have yet to be elucidated, we discuss approaches that can be taken that are aligned with regulatory guidance.

Prevalence of Salmonella and E. coli, and their resistance to antimicrobial agents, in farming communities in northern Thailand.

A cross-sectional pilot study was conducted in Chiang Mai, Thailand, to determine the prevalence of Salmonella and Escherichia coli in swine, broiler chickens and human workers from farms and abattoirs in northern Thailand, and compare their antimicrobial resistance profiles. Fecal samples and cloacal swabs were collected from 150 swine and 150 chickens at the farm. Fecal samples from swine, cloacal swabs from chickens, and carcass swabs from both animals were collected from 100 swine and 100 chickens at the abattoir. Stool samples were collected from 15 swine farm workers and seven chicken farm workers. Primary isolation and identification of Salmonella and E. coli were conducted using standard methods. In vitro susceptibility testing of Salmonella and E. coli was conducted using the broth microdilution method, based on the United States National Committee for Clinical Laboratory Standards (NCCLS) guidelines. The prevalence of Salmonella from swine and chicken samples ranged from 2% to 25%. The prevalence of E. coli in chickens and swine ranged from 36.8% to 47.6%. In humans, the prevalence of Salmonella was 15%, and the prevalence of E. coli ranged from 51% to 53%. Resistance in Salmonella was found for tetracycline (84.7%), nalidixic acid (27.1%), florfenicol (18.6%), ampicillin (13.6%), and ceftiofur (3.4%), and in E. coli for tetracycline (91.5%), nalidixic acid (67.4%), ampicillin (61.6%), florfenicol (51.8%), enrofloxacin (28.7%), ciprofloxacin (12.5%), ceftiofur (4.9%) and ceftriaxone (1.5%).