A novel coronavirus (CoV), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 in Wuhan, China and has since spread as a global pandemic. Safe and effective vaccines are thus urgently needed to reduce the significant morbidity and mortality of Coronavirus Disease 2019 (COVID-19) disease and ease the major economic impact. There has been an unprecedented rapid response by vaccine developers with now over one hundred vaccine candidates in development and at least six having reached clinical trials. However, a major challenge during rapid development is to avoid safety issues both by thoughtful vaccine design and by thorough evaluation in a timely manner. A syndrome of “disease enhancement” has been reported in the past for a few viral vaccines where those immunized suffered increased severity or death when they later encountered the virus or were found to have an increased frequency of infection. Animal models allowed scientists to determine the underlying mechanism for the former in the case of Respiratory syncytial virus (RSV) vaccine and have been utilized to design and screen new RSV vaccine candidates. Because some Middle East respiratory syndrome (MERS) and SARS-CoV-1 vaccines have shown evidence of disease enhancement in some animal models, this is a particular concern for SARS-CoV-2 vaccines. To address this challenge, the Coalition for Epidemic Preparedness Innovations (CEPI) and the Brighton Collaboration (BC) Safety Platform for Emergency vACcines (SPEAC) convened a scientific working meeting on March 12 and 13, 2020 of experts in the field of vaccine immunology and coronaviruses to consider what vaccine designs could reduce safety concerns and how animal models and immunological assessments in early clinical trials can help to assess the risk. This report summarizes the evidence presented and provides considerations for safety assessment of COVID-19 vaccine candidates in accelerated vaccine development.
【저자키워드】 COVID-19, SARS-CoV-2, COVID-19, Coronavirus disease 2019, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, animal models, ACE2, angiotensin-converting enzyme 2, SARS-CoV-2 vaccine, vaccine safety, RSV, respiratory syncytial virus, RBD, receptor binding domain, ARDS, acute respiratory distress syndrome, CRISPR, Clustered Regularly Interspaced Short Palindromic Repeats, WHO, World Health Organization, DNA, Deoxyribonucleic acid, CNS, Central Nervous System, DPP4, dipeptidyl peptidase-4, RNA, Ribonucleic acid, NTD, N Terminal Domain, Vaccine adjuvants, MERS-CoV vaccine, IHC, immunohistochemistry, MERS CoV, Middle East Respiratory Syndrome Coronavirus, MVA, Modified Vaccinia virus Ankara, mRNA, messenger RNA, SARS-CoV-1 vaccine, Enhanced disease, ADE, Antibody disease enhancement, B/HPIV3, Bovine/human parainfluenza virus type 3, BC, Brighton Collaboration, BPL, β-Propiolactone, BtCoV, Bat coronavirus, CEPI, Coalition for Epidemic Preparedness Innovations, hACE2, Human ACE2 receptor, HBs, Hepatitis B surface antigen, hDPP4, Human DPP4, NHP, Non-human primate, Non-SPF, Non-specific pathogen free, RAG1, Recombination activating gene 1, rMVA, Recombinant modified vaccinia virus Ankara, SARS-CoV-1, Severe acute respiratory syndrome coronavirus 1, SPEAC, Safety Platform for Emergency vACcines, TCR, T-cell receptor, Tg, Transgenic, Th1, T-helper cell type 1, Th2, T-helper cell type 2, VSV, Vesicular stomatitis virus,