ABSTRACT
Emergency use authorization of COVID vaccines has brought hope to mitigate pandemic of coronavirus disease 2019 (COVID-19). However, there remains a need for additional effective vaccines to meet the global demand and address the potential new viral variants. mRNA technologies offer an expeditious path alternative to traditional vaccine approaches. Here we describe the efforts to utilize an mRNA platform for rational design and evaluations of mRNA vaccine candidates based on the spike (S) glycoprotein of SARS-CoV-2. Several mRNA constructs of S-protein, including wild type, a pre-fusion stabilized mutant (2P), a furin cleavage-site mutant (GSAS) and a double mutant form (2P/GSAS), as well as others, were tested in animal models for their capacity to elicit neutralizing antibodies (nAbs). The lead 2P/GSAS candidate was further assessed in dose-ranging studies in mice and Cynomolgus macaques, and for efficacy in a Syrian golden hamster model. The selected 2P/GSAS vaccine formulation, designated MRT5500, elicited potent nAbs as measured in neutralization assays in all three preclinical models and more importantly, protected against SARS-CoV-2-induced weight loss and lung pathology in hamsters. In addition, MRT5500 elicited TH1-biased responses in both mouse and non-human primate (NHP), thus alleviating a hypothetical concern of potential vaccine-associated enhanced respiratory diseases known associated with TH2-biased responses. These data position MRT5500 as a viable vaccine candidate for entering clinical development.
ABSTRACT
OBJECTIVES: Green House and other small nursing home (NH) models are considered "nontraditional" due to their size (10-12 beds), universal caregivers, and other home-like features. They have garnered great interest regarding their potential benefit to limit Coronavirus Disease 2019 (COVID-19) infections due to fewer people living, working, visiting, and being admitted to Green House/small NHs, and private rooms and bathrooms, but this assumption has not been tested. If they prove advantageous compared with other NHs, they may constitute an especially promising model as policy makers and providers reinvent NHs post-COVID. DESIGN: This cohort study compared rates of COVID-19 infections, COVID-19 admissions/readmissions, and COVID-19 mortality, among Green House/small NHs with rates in other NHs between January 20, 2020 and July 31, 2020. SETTING AND PARTICIPANTS: All Green House homes that held a skilled nursing license and received Medicaid or Medicare payment were invited to participate; other small NHs that replicate Green House physical design and operational practices were eligible if they had the same licensure and payer sources. Of 57 organizations, 43 (75%) provided complete data, which included 219 NHs. Comparison NHs (referred to as "traditional NHs") were up to 5 most geographically proximate NHs within 100 miles that had <50 beds and ≥50 beds for which data were available from the Centers for Medicare and Medicaid Services (CMS). Because Department of Veterans Affairs organizations are not required to report to CMS, they were not included. METHODS: Rates per 1000 resident days were derived for COVID-19 cases and admissions, and per 100 COVID-19 positive cases for mortality. A log-rank test compared rates between Green House/small NHs and traditional NHs with <50 beds and ≥50 beds. RESULTS: Rates of all outcomes were significantly lower in Green House/small NHs than in traditional NHs that had <50 beds and ≥50 beds (log-rank test P < .025 for all comparisons). The median (middle value) rates of COVID-19 cases per 1000 resident days were 0 in both Green House/small NHs and NHs <50 beds, while they were 0.06 in NHs ≥50 beds; in terms of COVID-19 mortality, the median rates per 100 positive residents were 0 (Green House/small NHs), 10 (<50 beds), and 12.5 (≥50 beds). Differences were most marked in the highest quartile: 25% of Green House/small NHs had COVID-19 case rates per 1000 resident days higher than 0.08, with the corresponding figures for other NHs being 0.15 (<50 beds) and 0.74 (≥50 beds). CONCLUSIONS AND IMPLICATIONS: COVID-19 incidence and mortality rates are less in Green House/small NHs than rates in traditional NHs with <50 and ≥50 beds, especially among the higher and extreme values. Green House/small NHs are a promising model of care as NHs are reinvented post-COVID.