Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 10 de 10
Filter
1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-314835

ABSTRACT

Vaccines against SARS-CoV-2 are urgently required. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titers were boosted by a second dose. Data from these challenge models and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.

2.
Front Immunol ; 12: 629636, 2021.
Article in English | MEDLINE | ID: covidwho-1344259

ABSTRACT

Outbreaks that occur as a result of zoonotic spillover from an animal reservoir continue to highlight the importance of studying the disease interface between species. One Health approaches recognise the interdependence of human and animal health and the environmental interplay. Improving the understanding and prevention of zoonotic diseases may be achieved through greater consideration of these relationships, potentially leading to better health outcomes across species. In this review, special emphasis is given on the emerging and outbreak pathogen Crimean-Congo Haemorrhagic Fever virus (CCHFV) that can cause severe disease in humans. We discuss the efforts undertaken to better understand CCHF and the importance of integrating veterinary and human research for this pathogen. Furthermore, we consider the use of closely related nairoviruses to model human disease caused by CCHFV. We discuss intervention approaches with potential application for managing CCHFV spread, and how this concept may benefit both animal and human health.


Subject(s)
Hemorrhagic Fever, Crimean/prevention & control , Animals , Disease Models, Animal , Disease Reservoirs , Hemorrhagic Fever Virus, Crimean-Congo/pathogenicity , Hemorrhagic Fever, Crimean/epidemiology , Hemorrhagic Fever, Crimean/transmission , Humans , Viral Vaccines/immunology , Viral Zoonoses/prevention & control
3.
Commun Biol ; 4(1): 915, 2021 07 26.
Article in English | MEDLINE | ID: covidwho-1327224

ABSTRACT

Vaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.


Subject(s)
COVID-19 Vaccines/immunology , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/immunology , Ferrets , Macaca mulatta
5.
Nat Commun ; 12(1): 2893, 2021 05 17.
Article in English | MEDLINE | ID: covidwho-1232068

ABSTRACT

Several vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two-dose heterologous vaccination regimens than single-dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , RNA, Viral/administration & dosage , SARS-CoV-2/immunology , Vaccination/methods , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Immunization, Secondary , Immunogenicity, Vaccine , Mice , RNA, Viral/genetics , RNA, Viral/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes, Cytotoxic/immunology , Th1 Cells/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology
6.
Nat Med ; 27(2): 279-288, 2021 02.
Article in English | MEDLINE | ID: covidwho-1065913

ABSTRACT

More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18-55 years ( NCT04324606 ). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.


Subject(s)
Antibody Formation/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Immunization, Secondary , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Neutralizing/immunology , Dose-Response Relationship, Drug , Genetic Vectors/immunology , Humans , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , Time Factors , Young Adult
8.
NPJ Vaccines ; 5(1): 69, 2020.
Article in English | MEDLINE | ID: covidwho-689622

ABSTRACT

Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres.

9.
Nature ; 586(7830): 578-582, 2020 10.
Article in English | MEDLINE | ID: covidwho-691215

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the coronavirus disease 2019 (COVID-19) pandemic3. Vaccines are an essential countermeasure and are urgently needed to control the pandemic4. Here we show that the adenovirus-vector-based vaccine ChAdOx1 nCoV-19, which encodes the spike protein of SARS-CoV-2, is immunogenic in mice and elicites a robust humoral and cell-mediated response. This response was predominantly mediated by type-1 T helper cells, as demonstrated by the profiling of the IgG subclass and the expression of cytokines. Vaccination with ChAdOx1 nCoV-19 (using either a prime-only or a prime-boost regimen) induced a balanced humoral and cellular immune response of type-1 and type-2 T helper cells in rhesus macaques. We observed a significantly reduced viral load in the bronchoalveolar lavage fluid and lower respiratory tract tissue of vaccinated rhesus macaques that were challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated SARS-CoV-2-infected animals. However, there was no difference in nasal shedding between vaccinated and control SARS-CoV-2-infected macaques. Notably, we found no evidence of immune-enhanced disease after viral challenge in vaccinated SARS-CoV-2-infected animals. The safety, immunogenicity and efficacy profiles of ChAdOx1 nCoV-19 against symptomatic PCR-positive COVID-19 disease will now be assessed in randomized controlled clinical trials in humans.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Disease Models, Animal , Macaca mulatta , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Adenoviridae/genetics , Animals , Bronchoalveolar Lavage Fluid , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/genetics , Coronavirus Infections/virology , Cytokines/immunology , Female , Immunity, Cellular , Immunity, Humoral , Immunoglobulin G/immunology , Lung/immunology , Lung/pathology , Lung/virology , Macaca mulatta/immunology , Macaca mulatta/virology , Male , Mice , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Th1 Cells/immunology , Vaccination , Viral Load , Viral Vaccines/administration & dosage , Viral Vaccines/genetics
10.
Immunology ; 160(3): 223-232, 2020 07.
Article in English | MEDLINE | ID: covidwho-648052

ABSTRACT

Since the first World Health Organization notification on 31 December 2019, coronavirus disease 2019 (COVID-19), the respiratory disease caused by the coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been responsible for over four million confirmed infections and almost 300 000 deaths worldwide. The pandemic has led to over half of the world's population living under lockdown conditions. To allow normal life to resume, public health interventions will be needed to prevent further waves of infections as lockdown measures are lifted. As one of the most effective countermeasures against infectious diseases, an efficacious vaccine is considered crucial to containing the COVID-19 pandemic. Following the publication of the genome sequence of SARS-CoV-2, vaccine development has accelerated at an unprecedented pace across the world. Here we review the different platforms employed to develop vaccines, the standard timelines of development and how they can be condensed in a pandemic situation. We focus on vaccine development in the UK and vaccines that have entered clinical trials around the world.


Subject(s)
Viral Vaccines , Animals , COVID-19 , COVID-19 Vaccines , Clinical Trials as Topic , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Humans , Pandemics , Pneumonia, Viral/epidemiology , Protein Subunits/immunology , United Kingdom , Vaccines, Attenuated/immunology , Vaccines, DNA/immunology , Vaccines, Synthetic/immunology
SELECTION OF CITATIONS
SEARCH DETAIL