Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
1.
J Infect Dis ; 2021 Dec 11.
Article in English | MEDLINE | ID: covidwho-1566024

ABSTRACT

Co-circulation of SARS-CoV-2 and influenza viruses could pose unpredictable risks to health systems globally, with recent studies suggesting more severe disease outcomes in co-infected patients. The initial lack of a readily available COVID-19 vaccine has reinforced the importance of influenza vaccine programmes during the COVID-19 pandemic. Live Attenuated Influenza Vaccine (LAIV) is an important tool in protecting against influenza, particularly in children. However, it is unknown whether LAIV administration influences the outcomes of acute SARS-CoV-2 infection or disease. To investigate this, quadrivalent LAIV was administered to ferrets 3 days pre- or post-SARS-CoV-2 infection. LAIV administration did not exacerbate SARS-CoV-2 disease course or lung pathology with either regimen. Additionally, LAIV administered prior to SARS-CoV-2 infection significantly reduced SARS-CoV-2 replication and shedding in the upper respiratory tract. This study demonstrated that LAIV administration in close proximity to SARS-CoV-2 infection does not exacerbate mild disease and can reduce SARS-CoV-2 shedding.

3.
Vaccine ; 39(34): 4885-4894, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1284599

ABSTRACT

Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we assessed the safety, immunogenicity and efficacy of the intradermal delivery of INO-4800, a synthetic DNA vaccine candidate encoding the SARS-CoV-2 spike protein in the rhesus macaque model. Single and 2 dose vaccination regimens were evaluated. Vaccination induced both binding and neutralizing antibodies, along with IFN-γ-producing T cells against SARS-CoV-2. Upon administration of a high viral dose (5 × 106 pfu) via the intranasal and intratracheal routes we observed significantly reduced virus load in the lung and throat, in the vaccinated animals compared to controls. 2 doses of INO-4800 was associated with more robust vaccine-induced immune responses and improved viral protection. Importantly, histopathological examination of lung tissue provided no indication of vaccine-enhanced disease following SARS-CoV-2 challenge in INO-4800 immunized animals. This vaccine candidate is currently under clinical evaluation as a 2 dose regimen.


Subject(s)
COVID-19 , Vaccines, DNA , Viral Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Humans , Macaca mulatta , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
4.
Nat Commun ; 12(1): 81, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1007628

ABSTRACT

There is a vital need for authentic COVID-19 animal models to enable the pre-clinical evaluation of candidate vaccines and therapeutics. Here we report a dose titration study of SARS-CoV-2 in the ferret model. After a high (5 × 106 pfu) and medium (5 × 104 pfu) dose of virus is delivered, intranasally, viral RNA shedding in the upper respiratory tract (URT) is observed in 6/6 animals, however, only 1/6 ferrets show similar signs after low dose (5 × 102 pfu) challenge. Following sequential culls pathological signs of mild multifocal bronchopneumonia in approximately 5-15% of the lung is seen on day 3, in high and medium dosed groups. Ferrets re-challenged, after virus shedding ceased, are fully protected from acute lung pathology. The endpoints of URT viral RNA replication & distinct lung pathology are observed most consistently in the high dose group. This ferret model of SARS-CoV-2 infection presents a mild clinical disease.


Subject(s)
COVID-19/immunology , Disease Models, Animal , Ferrets/immunology , SARS-CoV-2/immunology , Animals , Antibodies, Viral/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/pharmacology , Dose-Response Relationship, Drug , Female , Lung/immunology , Lung/pathology , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , Virus Replication/drug effects , Virus Replication/immunology , Virus Shedding/drug effects , Virus Shedding/immunology
5.
EBioMedicine ; 63: 103153, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-956065

ABSTRACT

BACKGROUND: The novel human coronavirus SARS-CoV-2 is a major ongoing global threat with huge economic burden. Like all respiratory viruses, SARS-CoV-2 initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission. METHODS: SARS-CoV-2 Victoria/01/2020 was passaged in Vero/hSLAM cells and virus titre determined by plaque assay. Challenge virus was delivered by intranasal instillation to female ferrets at 5.0 × 106 pfu/ml. Treatment groups received intranasal INNA-051, developed by Ena Respiratory. SARS-CoV-2 RNA was detected using the 2019-nCoV CDC RUO Kit and QuantStudio™ 7 Flex Real-Time PCR System. Histopathological analysis was performed using cut tissues stained with haematoxylin and eosin (H&E). FINDINGS: We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. After 5 days post-exposure to SARS-CoV-2, INNA-051 significantly reduced virus in throat swabs (p=<0.0001) by up to a 24 fold (96% reduction) and in nasal wash (p=0.0107) up to a 15 fold (93% reduction) in comparison to untreated animals. INTERPRETATION: The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT, to reduce SARS-CoV-2 transmission and provide protection against COVID-19. FUNDING: This work was funded by Ena Respiratory, Melbourne, Australia.


Subject(s)
Lipopeptides/administration & dosage , Respiratory System/virology , SARS-CoV-2/pathogenicity , Toll-Like Receptor 2/agonists , Toll-Like Receptor 6/agonists , Virus Shedding , Administration, Intranasal , Animals , COVID-19/drug therapy , COVID-19/pathology , Disease Models, Animal , Female , Ferrets , Immunity, Innate , Lipopeptides/chemistry , Lipopeptides/pharmacology , Nasal Cavity/pathology , Nasal Cavity/virology , Pharynx/pathology , Pharynx/virology , RNA, Viral/metabolism , Real-Time Polymerase Chain Reaction , Respiratory System/pathology , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Viral Load/drug effects
SELECTION OF CITATIONS
SEARCH DETAIL
...