Your browser doesn't support javascript.
Шоу: 20 | 50 | 100
Результаты 1 - 20 de 3.572
Фильтр
Добавить фильтры

база данных
Годовой диапазон
1.
Theranostics ; 12(10): 4779-4790, 2022.
Статья в английский | MEDLINE | ID: covidwho-2203050

Реферат

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuing to spread globally, contributing to the persistence of the COVID-19 pandemic. Increasing resources have been focused on developing vaccines and therapeutics that target the Spike glycoprotein of SARS-CoV-2. Recent advances in microfluidics have the potential to recapitulate viral infection in the organ-specific platforms, known as organ-on-a-chip (OoC), in which binding of SARS-CoV-2 Spike protein to the angiotensin-converting enzyme 2 (ACE2) of the host cells occurs. As the COVID-19 pandemic lingers, there remains an unmet need to screen emerging mutations, to predict viral transmissibility and pathogenicity, and to assess the strength of neutralizing antibodies following vaccination or reinfection. Conventional detection of SARS-CoV-2 variants relies on two-dimensional (2-D) cell culture methods, whereas simulating the micro-environment requires three-dimensional (3-D) systems. To this end, analyzing SARS-CoV-2-mediated pathogenicity via microfluidic platforms minimizes the experimental cost, duration, and optimization needed for animal studies, and obviates the ethical concerns associated with the use of primates. In this context, this review highlights the state-of-the-art strategy to engineer the nano-liposomes that can be conjugated with SARS-CoV-2 Spike mutations or genomic sequences in the microfluidic platforms; thereby, allowing for screening the rising SARS-CoV-2 variants and predicting COVID-19-associated coagulation. Furthermore, introducing viral genomics to the patient-specific blood accelerates the discovery of therapeutic targets in the face of evolving viral variants, including B1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), c.37 (Lambda), and B.1.1.529 (Omicron). Thus, engineering nano-liposomes to encapsulate SARS-CoV-2 viral genomic sequences enables rapid detection of SARS-CoV-2 variants in the long COVID-19 era.


Тема - темы
COVID-19 , Coronavirus Infections , Pneumonia, Viral , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/complications , COVID-19/diagnosis , Coronavirus Infections/prevention & control , Genomics , Humans , Liposomes , Microfluidics , Mutation , Pandemics/prevention & control , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus
2.
Indian J Med Res ; 155(1): 105-122, 2022 01.
Статья в английский | MEDLINE | ID: covidwho-2201769

Реферат

The WHO emergency use-listed (EUL) COVID-19 vaccines were developed against early strains of SARS-CoV-2. With the emergence of SARS-CoV-2 variants of concern (VOCs) - Alpha, Beta, Gamma, Delta and Omicron, it is necessary to assess the neutralizing activity of these vaccines against the VOCs. PubMed and preprint platforms were searched for literature on neutralizing activity of serum from WHO EUL vaccine recipients, against the VOCs, using appropriate search terms till November 30, 2021. Our search yielded 91 studies meeting the inclusion criteria. The analysis revealed a drop of 0-8.9-fold against Alpha variant, 0.3-42.4-fold against Beta variant, 0-13.8-fold against Gamma variant and 1.35-20-fold against Delta variant in neutralization titres of serum from the WHO EUL COVID-19 vaccine recipients, as compared to early SARS-CoV-2 isolates. The wide range of variability was due to differences in the choice of virus strains selected for neutralization assays (pseudovirus or live virus), timing of serum sample collection after the final dose of vaccine (day 0 to 8 months) and sample size (ranging from 5 to 470 vaccinees). The reasons for this variation have been discussed and the possible way forward to have uniformity across neutralization assays in different laboratories have been described, which will generate reliable data. Though in vitro neutralization studies are a valuable tool to estimate the performance of vaccines against the backdrop of emerging variants, the results must be interpreted with caution and corroborated with field-effectiveness studies.


Тема - темы
COVID-19 , Viral Vaccines , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , SARS-CoV-2 , Viral Envelope Proteins
3.
Front Immunol ; 13: 918896, 2022.
Статья в английский | MEDLINE | ID: covidwho-2198845

Реферат

Background: Effective and safe vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are critical to controlling the COVID-19 pandemic and will remain the most important tool in limiting the spread of the virus long after the pandemic is over. Methods: We bring pioneering contributions on the maintenance of the immune response over a year on a real-life basis study in 1,587 individuals (18-90 yrs, median 39 yrs; 1,208 female/379 male) who underwent vaccination with two doses of CoronaVac and BNT162b2 booster after 6-months of primary protocol. Findings: Elevated levels of anti-spike IgG antibodies were detected after CoronaVac vaccination, which significantly decreased after 80 days and remained stable until the introduction of the booster dose. Heterologous booster restored antibody titers up to-1·7-fold, changing overall seropositivity to 96%. Titers of neutralising antibodies to the Omicron variant were lower in all timepoints than those against Delta variant. Individuals presenting neutralising antibodies against Omicron also presented the highest titers against Delta and anti-Spike IgG. Cellular immune response measurement pointed out a mixed immune profile with a robust release of chemokines, cytokines, and growth factors on the first month after CoronaVac vaccination followed by a gradual reduction over time and no increase after the booster dose. A stronger interaction between those mediators was noted over time. Prior exposure to the virus leaded to a more robust cellular immune response and a rise in antibody levels 60 days post CoronaVac than in individuals with no previous COVID-19. Both vaccines were safe and well tolerated among individuals. Interpretation: Our data approach the effectiveness of CoronaVac association with BNT162b2 from the clinical and biological perspectives, aspects that have important implications for informing decisions about vaccine boosters. Funding: Fiocruz, Brazil.


Тема - темы
COVID-19 Vaccines , COVID-19 , Immunization, Secondary , Immunogenicity, Vaccine , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine/immunology , Brazil , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Female , Follow-Up Studies , Humans , Immunoglobulin G , Male , Pandemics , SARS-CoV-2
4.
Front Immunol ; 13: 906551, 2022.
Статья в английский | MEDLINE | ID: covidwho-2198831

Реферат

Background: Zinc (Zn) is an essential trace element with high relevance for the immune system, and its deficiency is associated with elevated infection risk and severe disease course. The association of Zn status with the immune response to SARS-CoV-2 vaccination is unknown. Methods: A cohort of adult health care workers (n=126) received two doses of BNT162B2, and provided up to four serum samples over a time course of 6 months. Total SARS-CoV-2 IgG and neutralizing antibody potency was determined, along with total as well as free Zn concentrations. Results: The SARS-CoV-2 antibodies showed the expected rise in response to vaccination, and decreased toward the last sampling point, with highest levels measured three weeks after the second dose. Total serum Zn concentrations were relatively stable over time, and showed no significant association with SARS-CoV-2 antibodies. Baseline total serum Zn concentration and supplemental intake of Zn were both unrelated to the antibody response to SARS-CoV-2 vaccination. Time resolved analysis of free Zn indicated a similar dynamic as the humoral response. A positive correlation was observed between free Zn concentrations and both the induced antibodies and neutralizing antibody potency. Conclusion: While the biomarkers of Zn status and supplemental Zn intake appeared unrelated to the humoral immune response to SARS-CoV-2 vaccination, the observed correlation of free Zn to the induced antibodies indicates a diagnostic value of this novel biomarker for the immune system.


Тема - темы
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Vaccination , Zinc
5.
Front Cell Infect Microbiol ; 12: 978440, 2022.
Статья в английский | MEDLINE | ID: covidwho-2198706

Реферат

Purpose: This study was conducted in order to properly understand whether prior seasonal human coronavirus (HCoV) immunity could impact the potential cross-reactivity of humoral responses induced by SARS-CoV-2 vaccine, thereby devising universal coronavirus vaccines for future outbreaks. Methods: We performed enzyme-linked immunosorbent assay (ELISA) to quantify the immunoglobulin G (IgG) antibody levels to spike (S) protein and S1 subunit of HCoVs (HCoV-OC43, HCoV-HKU1, HCoV-NL63, and HCoV-229E), and ELISA [anti-RBD and anti-nucleoprotein (N)], chemiluminescence immunoassay assays (anti-RBD), pseudovirus neutralization test, and authentic viral neutralization test to detect the binding and neutralizing antibodies to SARS-CoV-2 in the vaccinees. Results: We found that the antibody of seasonal HCoVs did exist before vaccination and could be boosted by SARS-CoV-2 vaccine. A further analysis demonstrated that the prior S and S1 IgG antibodies of HCoV-OC43 were positively correlated with anti-RBD and neutralization antibodies to SARS-CoV-2 at 12 and 24 weeks after the second vaccination, and the correlation is more statistically significant at 24 weeks. The persistent antibody levels of SARS-CoV-2 were observed in vaccinees with higher pre-existing HCoV-OC43 antibodies. Conclusion: Our data indicate that inactivated SARS-CoV-2 vaccination may confer cross-protection against seasonal coronaviruses in most individuals, and more importantly, the pre-existing HCoV-OC43 antibody was associated with protective immunity to SARS-CoV-2, supporting the development of a pan-coronavirus vaccine.


Тема - темы
COVID-19 , Coronavirus OC43, Human , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunoglobulin G , SARS-CoV-2 , Vaccination
6.
Biopreserv Biobank ; 20(5): 423-428, 2022 Oct.
Статья в английский | MEDLINE | ID: covidwho-2188054

Реферат

Background: Antibodies with the specialized ability to fight infection can be found in the blood of individuals who have recovered from or have been vaccinated against COVID-19. As a result, plasma from these individuals could be used to treat critically ill patients. This treatment is known as convalescent plasma (CCP) therapy. Methods: Plasma units from 1555 consented healthy blood bank donors were collected from February to September 2021. Blood units were tested for the quantitative determination of Immunoglobulin G (IgG) antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus using one of the following assays based on the availability of the kits: The LIAISON® SARS-CoV-2 TrimericS IgG assay or the Abbott SARS-CoV-2 IgG II Quant assay. Results: Among the tested donors, 1027 participants tested positive for neutralizing anti-SARS-CoV-2 IgG antibodies (66.04%). There were 484 donors whose plasma qualified to be used for CCP therapy (47.13%) and 214 CCP units were stored in the COVID-19 convalescent biobank. Conclusion: We were able to identify and store 214 fresh frozen plasma units qualified for CCP-plasma therapy for COVID-19 patients according to World Health Organization standards. Hence, we established the first COVID-19-convalescent plasma data and plasma biobank for treating COVID-19-infected cancer patients in Jordan and the region.


Тема - темы
COVID-19 , SARS-CoV-2 , Humans , COVID-19/therapy , Antibodies, Viral , Jordan , Biological Specimen Banks , Antibodies, Neutralizing , Blood Donors , Immunoglobulin G , Plasma
7.
Eur J Cancer ; 171: 143-149, 2022 08.
Статья в английский | MEDLINE | ID: covidwho-2178267

Реферат

INTRODUCTION: The protective role against SARS-CoV-2 infection by the third booster dose of mRNA vaccines in cancer patients with solid malignancies is presently unknown. We prospectively investigated the occurrence of COVID-19 in cancer patients on active therapy after the booster vaccine dose. METHODS: Cancer patients on treatment at the Center for Immuno-Oncology (CIO) of the University Hospital of Siena, Italy, and health care workers at CIO who had received a booster third dose of mRNA vaccine entered a systematic follow-up monitoring period to prospectively assess their potential risk of SARS-CoV-2 infection. Serological and microneutralization assay were utilized to assess levels of anti-spike IgG, and of neutralizing antibodies to the SARS-CoV-2 Wild Type, Delta and Omicron variants, respectively, after the booster dose and after negativization of the nasopharyngeal swab for those who had developed COVID-19. RESULTS: Ninety cancer patients with solid tumors on active treatment (Cohort 1) and 30 health care workers (Cohort 2) underwent a booster third dose of mRNA vaccine. After the booster dose, the median value of anti-spike IgG was higher (p = 0.009) in patients than in healthy subjects. Remarkably, 11/90 (12%) patients and 11/30 (37%) healthy subjects tested positive to SARS-CoV-2 infection during the monitoring period. Similar levels of anti-spike IgG and of neutralizing antibodies against all the investigated variants, with geometric mean titers of neutralizing antibodies against the Omicron being the lowest were detected after the booster dose and after COVID-19 in both Cohorts. CONCLUSIONS: The occurrence of SARS-CoV-2 infection we observed in a sizable proportion of booster-dosed cancer patients and in healthy subjects during the Omicron outbreak indicates that highly specific vaccines against SARS-CoV-2 variants are urgently required.


Тема - темы
COVID-19 Vaccines , COVID-19 , Neoplasms , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Humans , Immunoglobulin G , Neoplasms/therapy , SARS-CoV-2 , Vaccines, Synthetic , Viral Envelope Proteins/genetics , mRNA Vaccines
9.
Front Immunol ; 13: 909910, 2022.
Статья в английский | MEDLINE | ID: covidwho-2163010

Реферат

Background: IgG anti-spike (S) antibodies arise after SARS-CoV-2 infection as well as vaccination. Levels of IgG anti-S are linked to neutralizing antibody titers and protection against (re)infection. Methods: We measured IgG anti-S and surrogate neutralizing antibody kinetics against Wild Type (WT) and 4 Variants of Concern (VOC) in health care workers (HCW) 3 and 10 months after natural infection ("infection", n=83) or vaccination (2 doses of BNT162b2) with ("hybrid immunity", n=17) or without prior SARS-CoV-2 infection ("vaccination", n=97). Results: The humoral immune response in the "vaccination" cohort was higher at 3 months, but lower at 10 months, compared to the "infection" cohort due to a faster decline. The "hybrid immunity" cohort had the highest antibody levels at 3 and 10 months with a slower decline compared to the "vaccination" cohort. Surrogate neutralizing antibody levels (expressed as %inhibition of ACE-2 binding) showed a linear relation with log10 of IgG anti-S against WT and four VOC. IgG anti-S corresponding to 90% inhibition ranged from 489 BAU/mL for WT to 1756 BAU/mL for Beta variant. Broad pseudoneutralization predicted live virus neutralization of Omicron BA.1 in 20 randomly selected high titer samples. Conclusions: Hybrid immunity resulted in the strongest humoral immune response. Antibodies induced by natural infection decreased more slowly than after vaccination, resulting in higher antibody levels at 10 months compared to vaccinated HCW without prior infection. There was a linear relationship between surrogate neutralizing activity and log10 IgG anti-S for WT and 4 VOC, although some VOC showed reduced sensitivity to pseudoneutralization.


Тема - темы
Antibodies, Neutralizing , COVID-19 , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , Health Personnel , Humans , Immunoglobulin G , SARS-CoV-2
10.
Sci Immunol ; 5(54)2020 12 23.
Статья в английский | MEDLINE | ID: covidwho-2161788

Реферат

Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.


Тема - темы
Antibodies, Neutralizing/immunology , Asymptomatic Infections , COVID-19/immunology , T-Lymphocytes/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibodies, Viral/immunology , Case-Control Studies , Cross-Sectional Studies , Humans , SARS-CoV-2/immunology
11.
Clin Lab Med ; 42(1): 57-73, 2022 03.
Статья в английский | MEDLINE | ID: covidwho-2130427

Реферат

The COVID-19 pandemic has resulted in the development, validation, and rapid adoption of multiple novel diagnostic approaches. Hundreds of SARS-CoV-2 serologic assays have been developed and deployed to contain the spread of the virus, and to supply timely and important health information. Most of these serologic assays were based on a conventional enzyme-linked immunosorbent assay or the lateral flow assay format. The immunoassays that were developed were based on alternative technologies and are highlighted in this article with a brief discussion of the assay principle and the pros and cons for each assay. Measurement of neutralizing antibodies is also discussed.


Тема - темы
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Enzyme-Linked Immunosorbent Assay , Humans , Pandemics , Sensitivity and Specificity
12.
Cell Host Microbe ; 30(11): 1540-1555.e15, 2022 11 09.
Статья в английский | MEDLINE | ID: covidwho-2130372

Реферат

The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency, but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5.


Тема - темы
COVID-19 , SARS-CoV-2 , Humans , Antibodies, Neutralizing , Antibodies, Viral , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics
13.
Infection ; 50(6): 1475-1481, 2022 Dec.
Статья в английский | MEDLINE | ID: covidwho-2129444

Реферат

BACKGROUND: The immune response to COVID-19-vaccination differs between naïve vaccinees and those who were previously infected with SARS-CoV-2. Longitudinal quantitative and qualitative serological differences in these two distinct immunological subgroups in response to vaccination are currently not well studied. METHODS: We investigate a cohort of SARS-CoV-2-naïve and COVID-19-convalescent individuals immediately after vaccination and 6 months later. We use different enzyme-linked immunosorbent assay (ELISA) variants and a surrogate virus neutralization test (sVNT) to measure IgG serum titers, IgA serum reactivity, IgG serum avidity and neutralization capacity by ACE2 receptor competition. RESULTS: Anti-receptor-binding domain (RBD) antibody titers decline over time in dually vaccinated COVID-19 naïves whereas titers in single dose vaccinated COVID-19 convalescents are higher and more durable. Similarly, antibody avidity is considerably higher among boosted COVID-19 convalescent subjects as compared to dually vaccinated COVID-19-naïve subjects. Furthermore, sera from boosted convalescents inhibited the binding of spike-protein to ACE2 more efficiently than sera from dually vaccinated COVID-19-naïve subjects. CONCLUSIONS: Long-term humoral immunity differs substantially between dually vaccinated SARS-CoV-2-naïve and COVID-19-convalescent individuals. Booster vaccination after COVID-19 induces a more durable humoral immune response in terms of magnitude and quality as compared to two-dose vaccination in a SARS-CoV-2-naïve background.


Тема - темы
COVID-19 , SARS-CoV-2 , Humans , COVID-19/prevention & control , Immunity, Humoral , Angiotensin-Converting Enzyme 2 , Immunoglobulin G , Antibodies, Viral , Antibodies, Neutralizing
15.
Viruses ; 14(10)2022 10 14.
Статья в английский | MEDLINE | ID: covidwho-2143679

Реферат

For more than two years after the emergence of COVID-19 (Coronavirus Disease-2019), significant regional differences in morbidity persist. These differences clearly show lower incidence rates in several regions of the African and Asian continents. The work reported here aimed to test the hypothesis of a pre-pandemic natural immunity acquired by some human populations in central and western Africa, which would, therefore, pose the hypothesis of an original antigenic sin with a virus antigenically close to the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To identify such pre-existing immunity, sera samples collected before the emergence of COVID-19 were tested to detect the presence of IgG reacting antibodies against SARS-CoV-2 proteins of major significance. Sera samples from French blood donors collected before the pandemic served as a control. The results showed a statistically significant difference of antibodies prevalence between the collected samples in Africa and the control samples collected in France. Given the novelty of our results, our next step consists in highlighting neutralizing antibodies to evaluate their potential for pre-pandemic protective acquired immunity against SARS-CoV-2. In conclusion, our results suggest that, in the investigated African sub-regions, the tested populations could have been potentially and partially pre-exposed, before the COVID-19 pandemic, to the antigens of a yet non-identified Coronaviruses.


Тема - темы
COVID-19 , SARS-CoV-2 , Humans , Pandemics , COVID-19/epidemiology , Spike Glycoprotein, Coronavirus , Antibodies, Neutralizing , Immunoglobulin G , Antibodies, Viral
16.
Viruses ; 14(9)2022 09 09.
Статья в английский | MEDLINE | ID: covidwho-2143622

Реферат

Evusheld® (tixagevimab + cilgavimab; AZD7442) was the first anti-Spike monoclonal antibody (mAb) cocktail designed not only for treatment but also with pre-exposure prophylaxis in mind. The immunoglobulins were engineered for prolonged half-life by modifying the Fc fragment, thus creating a long-acting antibody (LAAB). We review here preclinical development, baseline and treatment-emergent resistance, clinical efficacy from registration trials, and real-world post-marketing evidence. The combination was initially approved for pre-exposure prophylaxis at the time of the SARS-CoV-2 Delta VOC wave based on a trial conducted in unvaccinated subjects when the Alpha VOC was dominant. Another trial also conducted at the time of the Alpha VOC wave proved efficacy as early treatment in unvaccinated patients and led to authorization at the time of the BA.4/5 VOC wave. Tixagevimab was ineffective against any Omicron sublineage, so cilgavimab has so far been the ingredient which has made a difference. Antibody monotherapy has a high risk of selecting for immune escape variants in immunocompromised patients with high viral loads, which nowadays represent the main therapeutic indication for antibody therapies. Among Omicron sublineages, cilgavimab was ineffective against BA.1, recovered efficacy against BA.2 and BA.2.12.1, but lost efficacy again against BA.4/BA.5 and BA.2.75. Our analysis indicated that Evusheld® has been used during the Omicron VOC phase without robust clinical data of efficacy against this variant and suggested that several regulatory decisions regarding its use lacked consistency. There is an urgent need for new randomized controlled trials in vaccinated, immunocompromised subjects, using COVID-19 convalescent plasma as a control arm.


Тема - темы
COVID-19 , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , COVID-19/drug therapy , COVID-19/prevention & control , COVID-19/therapy , Clinical Trials as Topic , Drug Combinations , Humans , Immunization, Passive , Immunoglobulin Fc Fragments , SARS-CoV-2
17.
Front Immunol ; 13: 981693, 2022.
Статья в английский | MEDLINE | ID: covidwho-2142011

Реферат

Objectives: Emergence of new variants of SARS-CoV-2 might affect vaccine efficacy. Therefore, assessing the capacity of sera to neutralize variants of concern (VOCs) in BSL-2 conditions will help evaluating the immune status of population following vaccination or infection. Methods: Pseudotyped viruses bearing SARS-CoV-2 spike protein from Wuhan-Hu-1/D614G strains (wild type, WT), B.1.617.2 (Delta), or B.1.1.529 (Omicron) VOCs were generated to assess the neutralizing antibodies (nAbs) activity by a pseudovirus-based neutralization assay (PVNA). PVNA performance was assessed in comparison to the micro-neutralization test (MNT) based on live viruses. Sera collected from COVID-19 convalescents and vaccinees receiving mRNA (BNT16b2 or mRNA-1273) or viral vector (AZD1222 or Ad26.COV2.S) vaccines were used to measure nAbs elicited by two-dose BNT16b2, mRNA-1273, AZD1222 or one-dose Ad26.CO2.S, at different times from completed vaccination, ~ 1.5 month and ~ 4-6 months. Sera from pre-pandemic and unvaccinated individuals were analyzed as controls. Neutralizing activity following booster vaccinations against VOCs was also determined. Results: PVNA titers correlated with the gold standard MNT assay, validating the reliability of PVNA. Sera analyzed late from the second dose showed a reduced neutralization activity compared to sera collected earlier. Ad26.CO2.S vaccination led to very low or absent nAbs. Neutralization of Delta and Omicron BA.1 VOCs showed significant reduction of nAbs respect to WT strain. Importantly, booster doses enhanced Omicron BA.1 nAbs, with persistent levels at 3 months from boosting. Conclusions: PVNA is a reliable tool for assessing anti-SARS-CoV-2 nAbs helping the establishment of a correlate of protection and the management of vaccination strategies.


Тема - темы
COVID-19 , RNA Viruses , Ad26COVS1 , Antibodies, Neutralizing , COVID-19/prevention & control , Carbon Dioxide , ChAdOx1 nCoV-19 , Humans , Membrane Glycoproteins/metabolism , RNA, Messenger , Reproducibility of Results , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus , Viral Envelope Proteins
18.
Front Immunol ; 13: 947724, 2022.
Статья в английский | MEDLINE | ID: covidwho-2141980

Реферат

Background: Asthma patients potentially have impaired adaptive immunity to virus infection. The levels of SARS-CoV-2-specific adaptive immunity between COVID-19 survivors with and without asthma are presently unclear. Methods: COVID-19 survivors (patients with asthma n=11, with allergies n=8, and COVID-19 only n=17) and non-COVID-19 individuals (asthmatic patients n=10 and healthy controls n=9) were included. The COVID-19 patients were followed up at about 8 months and 16 months after discharge. The clinical characteristics, lymphocyte subsets, memory T cells, and humoral immunity including SARS-CoV-2 specific antibodies, SARS-CoV-2 pseudotyped virus neutralization assay, and memory B cells were analyzed in these subjects. Results: The strength of virus-specific T cell response in COVID-19 survivors was positively correlated with the percentage of blood eosinophils and Treg cells (r=0.4007, p=0.0188; and r=0.4435, p=0.0086 respectively) at 8-month follow-up. There were no statistical differences in the levels of SARS-CoV-2-specific T cell response between the COVID-19 survivors with, and without, asthma. Compared to those without asthma, the COVID-19 with asthma survivors had higher levels of SARS-CoV-2-specific neutralizing antibodies (NAbs) at the 8-month follow-up (p<0.05). Moreover, the level of NAbs in COVID-19 survivors was positively correlated with the percentage of Treg and cTfh2 cells (r=0.5037, p=0.002; and r=0.4846, p=0.0141), and negatively correlated with the percentage of Th1 and Th17 cells (r=-0.5701, p=0.0003; and r=-0.3656, p=0.0308), the ratio of Th1/Th2, Th17/Treg, and cTfh1/cTfh2 cell (r=-0.5356, r=-0.5947, r=-0.4485; all p<0.05). The decay rate of NAbs in the COVID-19 survivors with asthma was not significantly different from that of those without asthma at 16-month follow-up. Conclusion: The level of SARS-CoV-2-specific NAbs in COVID-19 survivors with asthma was higher than that of those without asthma at 8-month follow-up. The SARS-CoV-2-specific T cell immunity was associated with blood eosinophils and Treg percentages. The SARS-CoV-2-specific humoral immunity was closely associated with cTfh2/cTfh1 imbalance and Treg/Th17 ratio. According to the findings, asthmatic patients in COVID-19 convalescent period may benefit from an enhanced specific humoral immunity, which associates with skewed Th2/Th1 and Treg/Th17 immune.


Тема - темы
Asthma , COVID-19 , Adaptive Immunity , Antibodies, Neutralizing , Antibodies, Viral , Humans , SARS-CoV-2 , Survivors
19.
Front Immunol ; 13: 946318, 2022.
Статья в английский | MEDLINE | ID: covidwho-2141971

Реферат

Background and Methods: The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Omicron (B.1.1.529) variant is the antigenically most distinct variant to date. As the heavily mutated spike protein enables neutralization escape, we studied serum-neutralizing activities of naïve and vaccinated individuals after Omicron BA.1 or BA.2 sub-lineage infections in live virus neutralization tests with Omicron BA.1, Omicron BA.2, wildtype (WT, B1.1), and Delta (B.1.617.2) strains. Serum samples obtained after WT infections and three-dose mRNA vaccinations with and without prior infection were included as controls. Results: Primary BA.1 infections yielded reduced neutralizing antibody levels against WT, Delta, and Omicron BA.2, while samples from BA.2-infected individuals showed almost no cross-neutralization against the other variants. Serum neutralization of Omicron BA.1 and BA.2 variants was detectable after three-dose mRNA vaccinations, but with reduced titers. Vaccination-breakthrough infections with either Omicron BA.1 or BA.2, however, generated equal cross-neutralizing antibody levels against all SARS-CoV-2 variants tested. Conclusions: Our study demonstrates that although Omicron variants are able to enhance cross-neutralizing antibody levels in pre-immune individuals, primary infections with BA.1 or BA.2 induced mostly variant-specific neutralizing antibodies, emphasizing the differently shaped humoral immunity induced by the two Omicron variants. These data thus contribute substantially to the understanding of antibody responses induced by primary Omicron infections or multiple exposures to different SARS-CoV-2 variants and are of particular importance for developing vaccination strategies in the light of future emerging variants.


Тема - темы
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Broadly Neutralizing Antibodies , Humans , Membrane Glycoproteins , Neutralization Tests , RNA, Messenger , Spike Glycoprotein, Coronavirus/genetics , Viral Envelope Proteins
20.
PLoS Pathog ; 18(11): e1010951, 2022 Nov.
Статья в английский | MEDLINE | ID: covidwho-2140720

Реферат

SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.


Тема - темы
Angiotensin-Converting Enzyme 2 , COVID-19 , Humans , Angiotensin-Converting Enzyme 2/genetics , Spike Glycoprotein, Coronavirus , SARS-CoV-2/genetics , COVID-19/genetics , Antibodies, Neutralizing/chemistry , Mutation
Критерии поиска