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1.
Front Immunol ; 13: 1027924, 2022.
Article in English | MEDLINE | ID: covidwho-2119762

ABSTRACT

Objectives: We aimed to evaluate the duration and breadth of antibodies elicited by inactivated COVID-19 vaccinations in healthy blood donors. Methods: We performed serological tests on 1,417 samples from 658 blood donors who received two (n=357), or three (n=301) doses of COVID-19 inactivated vaccine. We also accessed the change in antibody response before and after booster vaccination in 94 participants and their neutralization breadth to the current variants after the booster. Results: Following vaccination, for either the 2- or 3-dose, the neutralizing antibodies (nAbs) peaked with about 97% seropositivity approximately within one month but subsequently decreased over time. Of plasmas collected 6-8 months after the last immunization, the nAb seropositivities were 37% and 85% in populations with 2-dose and 3-dose vaccinations, respectively. The nAbs of plasma samples (collected between 2-6 weeks after the 3rd dose) from triple-vaccinated donors (n=94) showed a geometric mean titer of 145.3 (95% CI: 117.2 to 180.1) against the ancestral B.1, slightly reduced by 1.7-fold against Delta variant, but markedly decreased by 4-6 fold in neutralizing Omicron variants, including the sub-lineages of BA.1 (5.6-fold), BA.1.1 (6.0-fold), BA.2 (4.2-fold), B.2.12.1 (6.2-fold) and BA.4/5 (6.5-fold). Conclusion: These findings suggested that the 3rd dose of inactivated COVID-19 vaccine prolongs the antibody duration in healthy populations, but the elicited-nAbs are less efficient in neutralizing circulating Omicron variants.


Subject(s)
Antibody Formation , COVID-19 , Humans , COVID-19 Vaccines , Blood Donors , COVID-19/prevention & control , SARS-CoV-2 , Antibodies, Neutralizing , Vaccination
2.
J Virol Methods ; 307: 114564, 2022 09.
Article in English | MEDLINE | ID: covidwho-1878302

ABSTRACT

The COVID-19 pandemic caused by SARS-CoV-2 infections has led to excess deaths worldwide. Neutralizing antibodies (nAbs) against viral spike protein acquired from natural infections or vaccinations contribute to protection against new- and re-infections. Besides neutralization, antibody-mediated cellular cytotoxicity (ADCC) and phagocytosis (ADCP) are also important for viral clearance. However, due to the lack of convenient methods, the ADCC and ADCP responses elicited by viral infections or vaccinations remain to be explored. Here, we developed cell-based assays using target cells stably expressing SARS-CoV-2 spikes and Jurkat-NFAT-CD16a/CD32a effector cells for ADCC/ADCP measurements of monoclonal antibodies and human convalescent COVID-19 plasmas (HCPs). In control samples (n = 190), the specificity was 99.5% (95%CI: 98.4-100%) and 97.4% (95%CI: 95.1-99.6%) for the ADCC and ADCP assays, respectively. Among 87 COVID-19 HCPs, 83 (sensitivity: 95.4%, 95%CI: 91.0-99.8%) and 81 (sensitivity: 93.1%, 95%CI: 87.8-98.4%) showed detectable ADCC (titer range: 7.4-1721.6) and ADCP activities (titer range: 4-523.2). Notably, both ADCC and ADCP antibody titers positively correlated with the nAb titers in HCPs. In summary, we developed new tools for quantitative ADCC and ADCP analysis against SARS-CoV-2, which may facilitate further evaluations of Fc-mediated effector functions in preventing and treating against SARS-CoV-2.


Subject(s)
Antibody-Dependent Cell Cytotoxicity , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 , Humans , Immunoassay/methods , Pandemics , Phagocytosis , SARS-CoV-2/chemistry , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism
3.
Biosens Bioelectron ; 203: 114032, 2022 May 01.
Article in English | MEDLINE | ID: covidwho-1729564

ABSTRACT

SARS-CoV-2 variants of concern (VOCs) contain several single-nucleotide variants (SNVs) at key sites in the receptor-binding region (RBD) that enhance infectivity and transmission, as well as cause immune escape, resulting in an aggravation of the coronavirus disease 2019 (COVID-19) pandemic. Emerging VOCs have sparked the need for a diagnostic method capable of simultaneously monitoring these SNVs. To date, no highly sensitive, efficient clinical tool exists to monitor SNVs simultaneously. Here, an encodable multiplex microsphere-phase amplification (MMPA) sensing platform that combines primer-coded microsphere technology with dual fluorescence decoding strategy to detect SARS-CoV-2 RNA and simultaneously identify 10 key SNVs in the RBD. MMPA limits the amplification refractory mutation system PCR (ARMS-PCR) reaction for specific target sequence to the surface of a microsphere with specific fluorescence coding. This effectively solves the problem of non-specific amplification among primers and probes in multiplex PCR. For signal detection, specific fluorescence codes inside microspheres are used to determine the corresponding relationship between the microspheres and the SNV sites, while the report probes hybridized with PCR products are used to detect the microsphere amplification intensity. The MMPA platform offers a lower SARS-CoV-2 RNA detection limit of 28 copies/reaction, the ability to detect a respiratory pathogen panel without cross-reactivity, and a SNV analysis accuracy level comparable to that of sequencing. Moreover, this super-multiple parallel SNVs detection method enables a timely updating of the panel of detected SNVs that accompanies changing VOCs, and presents a clinical availability that traditional sequencing methods do not.


Subject(s)
Biosensing Techniques , COVID-19 , COVID-19/diagnosis , Humans , Microspheres , Multiplex Polymerase Chain Reaction , Mutation , RNA, Viral/genetics , SARS-CoV-2/genetics
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