ABSTRACT
Niclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Though NIC is already FDA-approved, the oral formulation produces systemic drug levels that are too low to inhibit SARS-CoV-2. As an alternative, direct delivery of NIC to the respiratory tract as an aerosol could target the primary site of for SARS-CoV-2 acquisition and spread. We have developed a niclosamide powder suitable for delivery via dry powder inhaler, nebulizer, and nasal spray through the incorporation of human lysozyme (hLYS) as a carrier molecule. This novel formulation exhibits potent in vitro and in vivo activity against MERS-CoV and SARS-CoV-2 and may protect against methicillin-resistance staphylococcus aureus pneumonia and inflammatory lung damage occurring secondary to CoV infections. The suitability of the formulation for all stages of the disease and low-cost development approach will ensure wide-spread utilization
ABSTRACT
Severe acute respiratory syndrome coronavirus (SARS-CoV-2) has infected more than 16,000,000 people and has caused the death of more than 650,000 individuals since December 2019. A safe and effective vaccine that can provide herd immunity against SARS-CoV-2 is urgently needed to stop the spread of this virus among humans. Many human viral vaccines are live attenuated forms of viruses that elicit humoral and cellular immunity. Here, we describe the development of a cold-adapted live attenuated vaccine (SARS-CoV-2/human/Korea/CNUHV03-CA22{degrees}C/2020) by gradually adapting the growth of SARS-CoV-2 from 37{degrees}C to 22{degrees}C in Vero cells. This vaccine can be potentially administered to humans through nasal spray. Its single dose was observed to strongly induce the neutralising antibody (>640), cellular immunity, and mucosal IgA antibody in intranasally immunised K18-hACE2 mice, which are very susceptible to SARS-CoV-2 and SARS-CoV infection. The one-dose vaccinated mice were completely protected from SARS-CoV-2 infection and did not show loss of body weight, death, and the presence of virus in tissues, such as the nasal turbinates, brain, lungs, and kidneys. Taken together, the cold-adapted live attenuated SARS-CoV-2 vaccine developed by us may contribute to saving of human lives from the threat of SARS-CoV-2.
ABSTRACT
Recombinant DNA vaccines, based on plasmid vectors expressing an antigen under the control of a strong promotor, have several advantages over traditional vaccines. They have been shown to induce a full spectrum of immune responses for humoral and cellular systems and to secure the higher safety and the simplicity of administration. Thus, establishment of DNA vaccines against Newcastle disease virus (NDV) in poultry has been widely investigated using various virus strains and vector systems. In this study, the F and HN genes of NDV CBP-1 strains isolated from diseased pheasants and attenuated by serial passages in egg embryos were cloned using pSLIA vector and constructed two recombinants of pSLIA-tsF and pSLIA-tsHN. The recombinant plasmids were transfected into COS-7 cell and the expression of HN and F proteins were verified by immunofluorescence, SDS-PAGE and Western blot. The recombinant plasmids were injected intramuscularly and intradermally into C57B/6 mouse and a significant increment of HN and F antibodies was detected by ELISA. According to the results, it was implicative that the recombinant DNA could be utilized for development of recombinant DNA vaccine for NDV.
Subject(s)
Animals , Mice , Antibodies , Blotting, Western , Clone Cells , COS Cells , DNA, Recombinant , Electrophoresis, Polyacrylamide Gel , Embryonic Structures , Enzyme-Linked Immunosorbent Assay , Fluorescent Antibody Technique , Newcastle disease virus , Newcastle Disease , Ovum , Plasmids , Poultry , Serial Passage , Vaccines , Vaccines, DNAABSTRACT
Recent outbreaks of H5N1 avian influenza viruses in most Asian countries alert the imminent pandemic. Twenty-three humans out of 34 confirmed cases were dead of H5N1 infections. H9N2 avian influenza viruses are widespread in poultry in most Asian countries and infected humans in 1999 and 2003. H9N2 or H5N1 influenza viruses may cause a next pandemic. The extensive surveillance in poultry and pigs are very important for predicting a next pandemic. We performed the surveillance of avian influenza viruses in chickens sold in the live poultry markets. Only H9N2 subtypes of influenza viruses were isolated from chickens in the Korean live bird markets. Serological surveillance in chickens showed that chickens were infected with over 50% with H9N2 viruses. Antigenic analysis showed that current circulating H9N2 influenza viruses are distinct from those of Hong Kong and 1996 Korean isolates from chicken farms. Serological surveillance of pigs against H9N2 influenza viruses showed that over 20% are positive. To prepare the vaccine of H5N1 avian influenza viruses, reassortant viruses were made using the available reverse genetics. The efficacy and safety test of H5N1 candidate vaccine in monkeys showed that neutralization antibody were induced and no side effects such as fever and weight loss were observed.
Subject(s)
Animals , Humans , Asian People , Birds , Chickens , Disease Outbreaks , Fever , Haplorhini , Hong Kong , Influenza A Virus, H9N2 Subtype , Influenza in Birds , Orthomyxoviridae , Pandemics , Poultry , Reassortant Viruses , Reverse Genetics , Swine , Weight LossABSTRACT
Recent outbreaks of H5N1 avian influenza viruses in most Asian countries alert the imminent pandemic. Twenty-three humans out of 34 confirmed cases were dead of H5N1 infections. H9N2 avian influenza viruses are widespread in poultry in most Asian countries and infected humans in 1999 and 2003. H9N2 or H5N1 influenza viruses may cause a next pandemic. The extensive surveillance in poultry and pigs are very important for predicting a next pandemic. We performed the surveillance of avian influenza viruses in chickens sold in the live poultry markets. Only H9N2 subtypes of influenza viruses were isolated from chickens in the Korean live bird markets. Serological surveillance in chickens showed that chickens were infected with over 50% with H9N2 viruses. Antigenic analysis showed that current circulating H9N2 influenza viruses are distinct from those of Hong Kong and 1996 Korean isolates from chicken farms. Serological surveillance of pigs against H9N2 influenza viruses showed that over 20% are positive. To prepare the vaccine of H5N1 avian influenza viruses, reassortant viruses were made using the available reverse genetics. The efficacy and safety test of H5N1 candidate vaccine in monkeys showed that neutralization antibody were induced and no side effects such as fever and weight loss were observed.
