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1.
Med (N Y) ; 3(6): 422-432.e3, 2022 06 10.
Article in English | MEDLINE | ID: covidwho-1926778

ABSTRACT

Background: SARS-CoV-2 Omicron variant of concern (VOC) has evolved multiple mutations within the spike protein, raising concerns of increased antibody evasion. In this study, we assessed the neutralization potential of COVID-19 convalescent sera and sera from vaccinated individuals against ancestral SARS-CoV-2 and VOCs. Methods: The neutralizing activity of sera from 65 coronavirus disease (COVID-19) vaccine recipients and convalescent individuals against clinical isolates of ancestral SARS-CoV-2 and Beta, Delta, and Omicron VOCs was assessed using a micro-neutralization assay. Findings: Convalescent sera from unvaccinated individuals infected by the ancestral virus demonstrated reduced neutralization against Beta and Omicron VOCs. Sera from individuals that received three doses of the Pfizer or Moderna vaccines demonstrated reduced neutralization of the Omicron variant relative to ancestral SARS-CoV-2. Sera from individuals that were naturally infected with ancestral SARS-CoV-2 and subsequently received two doses of the Pfizer vaccine induced significantly higher neutralizing antibody levels against ancestral virus and all VOCs. Infection alone, either with ancestral SARS-CoV-2 or the Delta variant, was not sufficient to induce high neutralizing antibody titers against Omicron. Conclusions: In summary, we demonstrate that convalescent and vaccinated sera display varying levels of SARS-CoV-2 VOC neutralization. Data from this study will inform booster vaccination strategies against SARS-CoV-2 VOCs. Funding: This research was funded by the Canadian Institutes of Health Research (CIHR). VIDO receives operational funding from the Government of Saskatchewan through Innovation Saskatchewan and the Ministry of Agriculture and from the Canada Foundation for Innovation through the Major Science Initiatives for its CL3 facility.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19/therapy , Humans , Immunization, Passive , Membrane Glycoproteins/genetics , Neutralization Tests , SARS-CoV-2/genetics , Saskatchewan , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins/genetics
2.
Viruses ; 13(4)2021 04 15.
Article in English | MEDLINE | ID: covidwho-1208346

ABSTRACT

Many factors impact the host response to influenza virus infection and vaccination. Ferrets have been an indispensable reagent for influenza virus research for almost one hundred years. One of the most significant and well-known factors affecting human disease after infection is host age. Another significant factor is the virus, as strain-specific disease severity is well known. Studying age-related impacts on viral infection and vaccination outcomes requires an animal model that reflects both the physiological and immunological changes that occur with human aging, and sensitivity to differentially virulent influenza viruses. The ferret is uniquely susceptible to a plethora of influenza viruses impacting humans and has proven extremely useful in studying the clinical and immunological pictures of influenza virus infection. Moreover, ferrets developmentally have several of the age-related physiological changes that occur in humans throughout infancy, adulthood, old age, and pregnancy. In this review, we discuss ferret susceptibility to influenza viruses, summarize previous influenza studies using ferrets as models of age, and finally, highlight the application of ferret age models in the pursuit of prophylactic and therapeutic agents to address age-related influenza disease severity.


Subject(s)
Ferrets/virology , Immunity , Orthomyxoviridae Infections/virology , Age Factors , Animals , Female , Humans , Influenza Vaccines , Pregnancy , Risk Factors , Vaccination
3.
PLoS Pathog ; 17(7): e1009705, 2021 07.
Article in English | MEDLINE | ID: covidwho-1311291

ABSTRACT

COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is a disease affecting several organ systems. A model that captures all clinical symptoms of COVID-19 as well as long-haulers disease is needed. We investigated the host responses associated with infection in several major organ systems including the respiratory tract, the heart, and the kidneys after SARS-CoV-2 infection in Syrian hamsters. We found significant increases in inflammatory cytokines (IL-6, IL-1beta, and TNF) and type II interferons whereas type I interferons were inhibited. Examination of extrapulmonary tissue indicated inflammation in the kidney, liver, and heart which also lacked type I interferon upregulation. Histologically, the heart had evidence of myocarditis and microthrombi while the kidney had tubular inflammation. These results give insight into the multiorgan disease experienced by people with COVID-19 and possibly the prolonged disease in people with post-acute sequelae of SARS-CoV-2 (PASC).


Subject(s)
COVID-19/immunology , Down-Regulation/immunology , Interferon Type I/immunology , Kidney/immunology , Myocardium/immunology , Respiratory System/immunology , SARS-CoV-2/immunology , Animals , COVID-19/pathology , Cricetinae , Disease Models, Animal , Humans , Inflammation/immunology , Inflammation/pathology , Kidney/pathology , Kidney/virology , Male , Mesocricetus , Myocardium/pathology , Respiratory System/pathology , Respiratory System/virology
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