ABSTRACT
BACKGROUND: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. METHODS: We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. RESULTS: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. CONCLUSIONS: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.
Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antibodies, Neutralizing , Antibodies, Viral , Broadly Neutralizing Antibodies , COVID-19/prevention & control , Humans , Mice , SARS-CoV-2/genetics , Vaccines, Synthetic , mRNA VaccinesABSTRACT
The risk of developing coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) depends on factors related to the host, virus, and treatment. However, many hospitals have modified their existing rooms and adjusted airflow to protect healthcare workers from aerosolization, which may increase the risk of Aspergillus exposure. This study aimed to quantitatively investigate airborne fungal levels in negative and slightly negative pressure rooms for COVID-19 patients. The air in neutral pressure rooms in ordinary wards and a liver intensive care unit with high-efficiency particulate air filter was also assessed for comparison. We found the highest airborne fungal burden in recently renovated slightly negative air pressure rooms, and a higher airborne fungal concentration in both areas used to treat COVID-19 patients. The result provided evidence of the potential environmental risk of CAPA by quantitative microbiologic air sampling, which was scarcely addressed in the literature. Enhancing environmental infection control measures to minimize exposure to fungal spores should be considered. However, the clinical implications of a periodic basis to determine indoor airborne fungal levels and further air sterilization in these areas remain to be defined.
ABSTRACT
Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.
Subject(s)
COVID-19 , Communicable Diseases, Emerging , Disease Models, Animal , 3T3 Cells , Angiotensin-Converting Enzyme 2/genetics , Animals , Antibodies, Viral/immunology , Antibodies, Viral/therapeutic use , COVID-19/immunology , COVID-19/pathology , COVID-19/physiopathology , Chlorocebus aethiops , Dependovirus/genetics , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Transduction, Genetic , Vero CellsABSTRACT
The COVID-19 pandemic presents an unprecedented challenge to global public health. Rapid development and deployment of safe and effective vaccines are imperative to control the pandemic. In the current study, we applied our adjuvanted stable prefusion SARS-CoV-2 spike (S-2P)-based vaccine, MVC-COV1901, to hamster models to demonstrate immunogenicity and protection from virus challenge. Golden Syrian hamsters immunized intramuscularly with two injections of 1 µg or 5 µg of S-2P adjuvanted with CpG 1018 and aluminum hydroxide (alum) were challenged intranasally with SARS-CoV-2. Prior to virus challenge, the vaccine induced high levels of neutralizing antibodies with 10,000-fold higher IgG level and an average of 50-fold higher pseudovirus neutralizing titers in either dose groups than vehicle or adjuvant control groups. Six days after infection, vaccinated hamsters did not display any weight loss associated with infection and had significantly reduced lung pathology and most importantly, lung viral load levels were reduced to lower than detection limit compared to unvaccinated animals. Vaccination with either 1 µg or 5 µg of adjuvanted S-2P produced comparable immunogenicity and protection from infection. This study builds upon our previous results to support the clinical development of MVC-COV1901 as a safe, highly immunogenic, and protective COVID-19 vaccine.