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1.
Front Immunol ; 13: 836492, 2022.
Article in English | MEDLINE | ID: covidwho-1875412

ABSTRACT

Severe COVID-19 can be associated with a prothrombotic state, increasing risk of morbidity and mortality. The SARS-CoV-2 spike glycoprotein is purported to directly promote platelet activation via the S1 subunit and is cleaved from host cells during infection. High plasma concentrations of S1 subunit are associated with disease progression and respiratory failure during severe COVID-19. There is limited evidence on whether COVID-19 vaccine-induced spike protein is similarly cleaved and on the immediate effects of vaccination on host immune responses or hematology parameters. We investigated vaccine-induced S1 subunit cleavage and effects on hematology parameters using AZD1222 (ChAdOx1 nCoV-19), a simian, replication-deficient adenovirus-vectored COVID-19 vaccine. We observed S1 subunit cleavage in vitro following AZD1222 transduction of HEK293x cells. S1 subunit cleavage also occurred in vivo and was detectable in sera 12 hours post intramuscular immunization (1x1010 viral particles) in CD-1 mice. Soluble S1 protein levels decreased within 3 days and were no longer detectable 7-14 days post immunization. Intravenous immunization (1x109 viral particles) produced higher soluble S1 protein levels with similar expression kinetics. Spike protein was undetectable by immunohistochemistry 14 days post intramuscular immunization. Intramuscular immunization resulted in transiently lower platelet (12 hours) and white blood cell (12-24 hours) counts relative to vehicle. Similarly, intravenous immunization resulted in lower platelet (24-72 hours) and white blood cell (12-24 hours) counts, and increased neutrophil (2 hours) counts. The responses observed with either route of immunization represent transient hematologic changes and correspond to expected innate immune responses to adenoviral infection.


Subject(s)
COVID-19 , Hematology , Viral Vaccines , Animals , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , ChAdOx1 nCoV-19 , Humans , Mice , Mice, Inbred BALB C , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
2.
Vaccine ; 40(2): 192-195, 2022 01 21.
Article in English | MEDLINE | ID: covidwho-1550127

ABSTRACT

Biodistribution studies of adenovirus-based vaccines support their clinical development by evaluating their spread and persistence following in vivo administration. AZD1222 (ChAdox1 nCov-19) is a replication-deficient non-human adenovirus-vectored vaccine for coronavirus disease 2019. In this nonclinical study, the biodistribution of AZD1222 was assessed in mice for 29 days following intramuscular injection. Results show that AZD1222 was safe and well tolerated, with a spread that was largely confined to administration sites and the proximal sciatic nerve, with low levels observed in sites that are involved in rapid clearance of particulates by the reticuloendothelial system. Accordingly, levels of AZD1222 decreased from Day 2 to Day 29, indicating clearance. There were no quantifiable levels of AZD1222 in the blood, brain, spinal cord, and reproductive tissue, suggesting a lack of widespread or long-term distribution of AZD1222 vector DNA throughout the body following its administration.


Subject(s)
COVID-19 , Animals , COVID-19 Vaccines , Humans , Mice , SARS-CoV-2 , Tissue Distribution
3.
Bioanalysis ; 13(19): 1459-1465, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1450902

ABSTRACT

During the first half of 2021, and due to the SARS-CoV-2 pandemic preventing in-person meetings, the European Bioanalysis Forum organized four workshops as live interactive online meetings. The themes discussed at the workshops were carefully selected to match the cyberspace dynamics of the meeting format. The first workshop was a training day on challenges related to immunogenicity. The second one focused on biomarkers and continued the important discussion on integrating the principles of Context of Use (CoU) in biomarker research. The third workshop was dedicated to technology, that is, cutting-edge development in cell-based and ligand-binding assays and automation strategies. The fourth was on progress and the continued scientific and regulatory challenges related to peptide and protein analysis with MS. In all four workshops, the European Bioanalysis Forum included a mixture of scientific and regulatory themes, while reminding the audience of important strategic aspects and our responsibility toward the patient.


Subject(s)
Chemistry Techniques, Analytical , Mass Spectrometry , Proteins/analysis , Proteins/immunology , Automation , Biomarkers/analysis , Humans , Proteins/chemistry
4.
Reprod Toxicol ; 104: 134-142, 2021 09.
Article in English | MEDLINE | ID: covidwho-1331182

ABSTRACT

AZD1222 (ChAdOx1 nCoV-19) is a COVID-19 vaccine that is not yet licensed for use during pregnancy. To support the inclusion of pregnant and breastfeeding people in AZD1222 clinical studies, a non-clinical developmental and reproductive toxicity study was performed to evaluate its effects on fertility and reproductive processes of female CD-1 mice during the embryofetal development phase, and postnatal outcomes during the littering phase. Immunogenicity assessments were also made in dams, fetuses, and pups. There were no vaccine-related unscheduled deaths throughout the study. Furthermore, there were no vaccine-related effects on female reproduction, fetal or pup survival, fetal external, visceral, or skeletal findings, pup physical development, and no abnormal gross pathology findings in pups or dams. Antibody responses raised in dams were maintained throughout gestation and postnatal periods, and seroconversion in fetuses and pups indicate placental and lactational transfer of immunoglobulins. Together with clinical data from non-pregnant people, these results support the inclusion of pregnant and breastfeeding people in AZD1222 clinical studies.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/administration & dosage , Immunogenicity, Vaccine , Vaccination , Animals , Biomarkers/blood , COVID-19 Vaccines/toxicity , Female , Fetus/drug effects , Fetus/immunology , Fetus/metabolism , Gestational Age , Lactation/immunology , Lactation/metabolism , Maternal-Fetal Exchange , Mice , Placenta/immunology , Placenta/metabolism , Pregnancy , Prenatal Exposure Delayed Effects , Risk Assessment , Seroconversion
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