Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
2.
Int J Mol Sci ; 23(6)2022 Mar 21.
Article in English | MEDLINE | ID: covidwho-1753508

ABSTRACT

Growing cases of patients reported have shown a potential relationship between (severe acute respiratory syndrome coronavirus 2) SARS-CoV-2 infection and Parkinson's disease (PD). However, it is unclear whether there is a molecular link between these two diseases. Alpha-synuclein (α-Syn), an aggregation-prone protein, is considered a crucial factor in PD pathology. In this study, bioinformatics analysis confirmed favorable binding affinity between α-Syn and SARS-CoV-2 spike (S) protein and nucleocapsid (N) protein, and direct interactions were further verified in HEK293 cells. The expression of α-Syn was upregulated and its aggregation was accelerated by S protein and N protein. It was noticed that SARS-CoV-2 proteins caused Lewy-like pathology in the presence of α-Syn overexpression. By confirming that SARS-CoV-2 proteins directly interact with α-Syn, our study offered new insights into the mechanism underlying the development of PD on the background of COVID-19.


Subject(s)
COVID-19 , Parkinson Disease , HEK293 Cells , Humans , Lewy Bodies/metabolism , Parkinson Disease/metabolism , SARS-CoV-2 , alpha-Synuclein/metabolism
3.
Clin Infect Dis ; 73(11): e3949-e3955, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1561940

ABSTRACT

BACKGROUND: We evaluated an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for immunogenicity and safety in adults aged 18-59 years. METHODS: In this randomized, double-blinded, controlled trial, healthy adults received a medium dose (MD) or a high dose (HD) of the vaccine at an interval of either 14 days or 28 days. Neutralizing antibody (NAb) and anti-S and anti-N antibodies were detected at different times, and adverse reactions were monitored for 28 days after full immunization. RESULTS: A total of 742 adults were enrolled in the immunogenicity and safety analysis. Among subjects in the 0, 14 procedure, the seroconversion rates of NAb in MD and HD groups were 89% and 96% with geometric mean titers (GMTs) of 23 and 30, respectively, at day 14 and 92% and 96% with GMTs of 19 and 21, respectively, at day 28 after immunization. Anti-S antibodies had GMTs of 1883 and 2370 in the MD group and 2295 and 2432 in the HD group. Anti-N antibodies had GMTs of 387 and 434 in the MD group and 342 and 380 in the HD group. Among subjects in the 0, 28 procedure, seroconversion rates for NAb at both doses were both 95% with GMTs of 19 at day 28 after immunization. Anti-S antibodies had GMTs of 937 and 929 for the MD and HD groups, and anti-N antibodies had GMTs of 570 and 494 for the MD and HD groups, respectively. No serious adverse events were observed during the study period. CONCLUSIONS: Adults vaccinated with inactivated SARS-CoV-2 vaccine had NAb as well as anti-S/N antibody and had a low rate of adverse reactions. CLINICAL TRIALS REGISTRATION: NCT04412538.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Double-Blind Method , Humans , Immunogenicity, Vaccine
4.
Mol Ther Methods Clin Dev ; 23: 108-118, 2021 Dec 10.
Article in English | MEDLINE | ID: covidwho-1379195

ABSTRACT

Because of the relatively limited understanding of coronavirus disease 2019 (COVID-19) pathogenesis, immunological analysis for vaccine development is needed. Mice and macaques were immunized with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine prepared by two inactivators. Various immunological indexes were tested, and viral challenges were performed on day 7 or 150 after booster immunization in monkeys. This inactivated SARS-CoV-2 vaccine was produced by sequential inactivation with formaldehyde followed by propiolactone. The various antibody responses and specific T cell responses to different viral antigens elicited in immunized animals were maintained for longer than 150 days. This comprehensive immune response could effectively protect vaccinated macaques by inhibiting viral replication in macaques and substantially alleviating immunopathological damage, and no clinical manifestation of immunopathogenicity was observed in immunized individuals during viral challenge. This candidate inactivated vaccine was identified as being effective against SARS-CoV-2 challenge in rhesus macaques.

5.
Food Chem Toxicol ; 152: 112239, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1202176

ABSTRACT

The outbreak of COVID-19 has posed a serious threat to global public health. Vaccination may be the most effective way to prevent and control the spread of the virus. The safety of vaccines is the focus of preclinical research, and the repeated dose toxicity test is the key safety test to evaluate the vaccine before clinical trials. The purpose of this study was (i) to observe the toxicity and severity of an inactivated SARS-CoV-2 vaccine (Vero cells) in rodent Sprague Dawley rats after multiple intramuscular injections under the premise of Good Laboratory Practice principles and (ii) to provide a basis for the formulation of a clinical trial scheme. The results showed that all animals in the experimental group were in good condition, no regular changes related to the vaccine were found in the detection of various toxicological indexes, and no noticeable stimulating reaction related to the vaccine was found in the injected local tissues. The neutralizing antibodies in the low- and high-dose vaccine groups began to appear 14 days after the last administration. In the negative control group, no neutralizing antibodies were observed from the administration period to the recovery period. Therefore, the repeated administration toxicity test of the inactivated SARS-CoV-2 vaccine (Vero cells) in Sprague Dawley rats showed no obvious toxic reaction. It was preliminarily confirmed that the vaccine can stimulate production of neutralizing antibodies and is safe in Sprague Dawley rats.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , Animals , COVID-19 , COVID-19 Vaccines/toxicity , Female , Male , Rats, Sprague-Dawley , Toxicity Tests , Vaccines, Inactivated/immunology , Vaccines, Inactivated/toxicity
6.
Vaccine ; 39(20): 2746-2754, 2021 05 12.
Article in English | MEDLINE | ID: covidwho-1174522

ABSTRACT

BACKGROUND: This study examined the safety and immunogenicity of an inactivated SARS-CoV-2 vaccine. METHOD: In a phase I randomized, double-blinded, placebo-controlled trial involving 192 healthy adults 18-59 years old, two injections of three doses (50 EU, 100 EU, 150 EU) of an inactivated SARS-CoV-2 vaccine or placebo were administered intramuscularly at a 2- or 4-week interval. The safety and immunogenicity of the vaccine were evaluated. RESULTS: Vaccination was completed in 191 subjects. Forty-four adverse reactions occurred within 28 days, most commonly mild pain and redness at the injection site or slight fatigue. At days 14 and 28, the seroconversion rates were 87.5% and 79.2% (50 EU), 100% and 95.8% (100 EU), and 95.8% and 87.5% (150 EU), respectively, with geometric mean titers (GMTs) of 18.1 and 10.6, 54.5 and 15.4, and 37.1 and 18.5, respectively, for the schedules with 2-week and 4-week intervals. Seroconversion was associated with synchronous upregulation of antibodies against the S protein, N protein and virion and a cytotoxic T lymphocyte (CTL) response. No cytokines and immune cells related to immunopathology were observed. Transcriptome analysis revealed the genetic diversity of immune responses induced by the vaccine. INTERPRETATION: In a population aged 18-59 years in this trial, this inactivated SARS-CoV-2 vaccine was safe and immunogenic. TRIAL REGISTRATION: CTR20200943 and NCT04412538.


Subject(s)
COVID-19 Vaccines , COVID-19 , Vaccines , Adolescent , Adult , Antibodies, Viral , China , Double-Blind Method , Humans , Immunogenicity, Vaccine , Middle Aged , SARS-CoV-2 , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL