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1.
Theranostics ; 12(10): 4779-4790, 2022.
Article in English | MEDLINE | ID: covidwho-2203050

ABSTRACT

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.


Subject(s)
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.
Article in English | MEDLINE | ID: covidwho-2201769

ABSTRACT

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.


Subject(s)
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.
Article in English | MEDLINE | ID: covidwho-2198845

ABSTRACT

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.


Subject(s)
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.
Article in English | MEDLINE | ID: covidwho-2198831

ABSTRACT

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.


Subject(s)
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.
Article in English | MEDLINE | ID: covidwho-2198706

ABSTRACT

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.


Subject(s)
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.
Article in English | MEDLINE | ID: covidwho-2188054

ABSTRACT

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.


Subject(s)
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.
Article in English | MEDLINE | ID: covidwho-2178267

ABSTRACT

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.


Subject(s)
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
8.
Front Immunol ; 13: 909910, 2022.
Article in English | MEDLINE | ID: covidwho-2163010

ABSTRACT

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.


Subject(s)
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.
Article in English | MEDLINE | ID: covidwho-2161788

ABSTRACT

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.


Subject(s)
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.
PLoS Pathog ; 18(11): e1010951, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2140720

ABSTRACT

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.


Subject(s)
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
12.
PLoS One ; 17(9): e0274181, 2022.
Article in English | MEDLINE | ID: covidwho-2140508

ABSTRACT

Quantitative measurement of SARS-CoV-2 neutralizing antibodies is highly expected to evaluate immune status, vaccine response, and antiviral therapy. The Elecsys® Anti-SARS-CoV-2 S (Elecsys® anti-S) was developed to measure anti-SARS-CoV-2 S proteins. We sought to investigate whether Elecsys® anti-S can be used to predict neutralizing activities in patients' serums using an authentic virus neutralization assay. One hundred forty-six serum samples were obtained from 59 patients with COVID-19 at multiple time points. Of the 59 patients, 44 cases were included in Group M (mild 23, moderate 21) and produced 84 samples (mild 35, moderate 49), while 15 cases were included in Group S (severe 11, critical 4) and produced 62 samples (severe 43, critical 19). The neutralization assay detected 73% positive cases, and Elecsys® anti-S and Elecsys® Anti-SARS-CoV-2 (Elecsys® anti-N) showed 72% and 66% positive cases, respectively. A linear correlation between the Elecsys® anti-S assay and the neutralization assay were highly correlated (r = 0.7253, r2 = 0.5261) than a linear correlation between the Elecsys® anti-N and neutralization assay (r = 0.5824, r2 = 0.3392). The levels of Elecsys® anti-S antibody and neutralizing activities were significantly higher in Group S than in Group M after 6 weeks from onset of symptoms (p < 0.05). Conversely, the levels of Elecsys® anti-N were comparable in both groups. Three immunosuppressed patients, including cancer patients, showed low levels of anti-S and anti-N antibodies and neutralizing activities throughout the measurement period, indicating the need for careful follow-up. Our data indicate that Elecsys® anti-S can predict the neutralization antibodies in COVID-19.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Antibodies, Viral , Antiviral Agents , COVID-19/diagnosis , Humans , Immunoassay , Neutralization Tests , SARS-CoV-2
13.
PLoS One ; 17(6): e0267796, 2022.
Article in English | MEDLINE | ID: covidwho-2140390

ABSTRACT

The current global COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a public health crisis with more than 168 million cases reported globally and more than 4.5 million deaths at the time of writing. In addition to the direct impact of the disease, the economic impact has been significant as public health measures to contain or reduce the spread have led to country wide lockdowns resulting in near closure of many sectors of the economy. Antibodies are a principal determinant of the humoral immune response to COVID-19 infections and may have the potential to reduce disease and spread of the virus. The development of monoclonal antibodies (mAbs) represents a therapeutic option that can be produced at large quantity and high quality. In the present study, a mAb combination mixture therapy was investigated for its capability to specifically neutralize SARS-CoV-2. We demonstrate that each of the antibodies bind the spike protein and neutralize the virus, preventing it from infecting cells in an in vitro cell-based assay, including multiple viral variants that are currently circulating in the human population. In addition, we investigated the effects of two different mutations in the Fc portion (YTE and LALA) of the antibody on Fc effector function and the ability to alleviate potential antibody-dependent enhancement of disease. These data demonstrate the potential of a combination of two mAbs that target two different epitopes on the SARS-CoV2 spike protein to provide protection against SARS-CoV-2 infection in humans while extending serum half-life and preventing antibody-dependent enhancement of disease.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing , Antibodies, Viral/therapeutic use , COVID-19/drug therapy , Communicable Disease Control , Humans , Pandemics , RNA, Viral , Spike Glycoprotein, Coronavirus
14.
Ann Clin Microbiol Antimicrob ; 21(1): 51, 2022 Nov 19.
Article in English | MEDLINE | ID: covidwho-2139308

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) causes life-threatening pneumonia. Convalescent plasma therapy (CPT) is expected to be the effective COVID-19 treatment for passive immunity. The high neutralizing antibodies titer of CPT is needed to prove the benefit in early developed severe COVID-19. OBJECTIVE: This case-control study evaluated transfusion efficacy and adverse events with high-titer (≥ 1:320) COVID-19 convalescent plasma compared with standard care alone in severe COVID-19 pneumonia. RESULTS: Among 107 severe COVID-19 patients, 55 received CPT plus standard care, and 52 received standard care alone. All-cause mortality was 15.3% in the CPT group compared with 85.4% in the standard care group (p < 0.001). Univariate and multivariate analyses revealed reduced mortality with CPT (HR 0.14; 95% CI 0.07-0.31; p < 0.001 and HR 0.26; 95% CI 0.08-0.79; p = 0.018, respectively). CPT resulted in decreased use of mechanical ventilation, duration of supplemental oxygen, and high-flow oxygen requirement. Clinical and radiological outcomes improved. CONCLUSIONS: Immediate high neutralizing antibody titer CPT is safe and reduces mortality in early developed severe COVID-19 patients. The benefit of CPT in the early course of illness is challenging and requires additional study. Trial registration Thai clinical trials registry (TCTR) no. 20220101003.


Subject(s)
Antibodies, Neutralizing , COVID-19 , Humans , COVID-19/therapy , Case-Control Studies , Immunization, Passive
15.
J Biomed Sci ; 29(1): 37, 2022 Jun 09.
Article in English | MEDLINE | ID: covidwho-2139298

ABSTRACT

BACKGROUND: Calls for the coronavirus to be treated as an endemic illness, such as the flu, are increasing. After achieving high coverage of COVID-19 vaccination, therapeutic drugs have become important for future SARS-CoV-2 variant outbreaks. Although many monoclonal antibodies have been approved for emergency use as treatments for SARS-CoV-2 infection, some monoclonal antibodies are not authorized for variant treatment. Broad-spectrum monoclonal antibodies are unmet medical needs. METHODS: We used a DNA prime-protein boost approach to generate high-quality monoclonal antibodies. A standard ELISA was employed for the primary screen, and spike protein-human angiotensin-converting enzyme 2 blocking assays were used for the secondary screen. The top 5 blocking clones were selected for further characterization, including binding ability, neutralization potency, and epitope mapping. The therapeutic effects of the best monoclonal antibody against SARS-CoV-2 infection were evaluated in a hamster infection model. RESULTS: Several monoclonal antibodies were selected that neutralize different SARS-CoV-2 variants of concern (VOCs). These VOCs include Alpha, Beta, Gamma, Delta, Kappa and Lambda variants. The high neutralizing antibody titers against the Beta variant would be important to treat Beta-like variants. Among these monoclonal antibodies, mAb-S5 displays the best potency in terms of binding affinity and neutralizing capacity. Importantly, mAb-S5 protects animals from SARS-CoV-2 challenge, including the Wuhan strain, D614G, Alpha and Delta variants, although mAb-S5 exhibits decreased neutralization potency against the Delta variant. Furthermore, the identified neutralizing epitopes of monoclonal antibodies are all located in the receptor-binding domain (RBD) of the spike protein but in different regions. CONCLUSIONS: Our approach generates high-potency monoclonal antibodies against a broad spectrum of VOCs. Multiple monoclonal antibody combinations may be the best strategy to treat future SARS-CoV-2 variant outbreaks.


Subject(s)
Antibodies, Monoclonal , COVID-19 , SARS-CoV-2 , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Neutralizing/therapeutic use , Antibodies, Viral/therapeutic use , COVID-19/drug therapy , COVID-19 Vaccines , Cricetinae , Humans , Spike Glycoprotein, Coronavirus/genetics
16.
Commun Biol ; 5(1): 1179, 2022 Nov 04.
Article in English | MEDLINE | ID: covidwho-2133651

ABSTRACT

Understanding the antigenic signatures of all human coronaviruses (HCoVs) Spike (S) proteins is imperative for pan-HCoV epitopes identification and broadly effective vaccine development. To depict the currently elusive antigenic signatures of α-HCoVs S proteins, we isolated a panel of antibodies against the HCoV-229E S protein and characterized their epitopes and neutralizing potential. We found that the N-terminal domain of HCoV-229E S protein is antigenically dominant wherein an antigenic supersite is present and appears conserved in HCoV-NL63, which holds potential to serve as a pan-α-HCoVs epitope. In the receptor binding domain, a neutralizing epitope is captured in the end distal to the receptor binding site, reminiscent of the locations of the SARS-CoV-2 RBD cryptic epitopes. We also identified a neutralizing antibody that recognizes the connector domain, thus representing the first S2-directed neutralizing antibody against α-HCoVs. The unraveled HCoVs S proteins antigenic similarities and variances among genera highlight the challenges faced by pan-HCoV vaccine design while supporting the feasibility of broadly effective vaccine development against a subset of HCoVs.


Subject(s)
COVID-19 , Coronavirus 229E, Human , Humans , Spike Glycoprotein, Coronavirus/genetics , SARS-CoV-2 , Antigens, Viral , Epitopes , Antibodies, Neutralizing
17.
Sci Rep ; 12(1): 20120, 2022 Nov 22.
Article in English | MEDLINE | ID: covidwho-2133636

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Variants of concern (VOCs) such as Delta and Omicron have developed, which continue to spread the pandemic. It has been reported that these VOCs reduce vaccine efficacy and evade many neutralizing monoclonal antibodies (mAbs) that target the receptor binding domain (RBD) of the glycosylated spike (S) protein, which consists of the S1 and S2 subunits. Therefore, identification of optimal target regions is required to obtain neutralizing antibodies that can counter VOCs. Such regions have not been identified to date. We obtained 2 mAbs, NIBIC-71 and 7G7, using peripheral blood mononuclear cells derived from volunteers who recovered from COVID-19. Both mAbs had neutralizing activity against wild-type SARS-CoV-2 and Delta, but not Omicron. NIBIC-71 binds to the RBD, whereas 7G7 recognizes the N-terminal domain of the S1. In particular, 7G7 inhibited S1/S2 cleavage but not the interaction between the S protein and angiotensin-converting enzyme 2; it suppressed viral entry. Thus, the efficacy of a neutralizing mAb targeting inhibition of S1/2 cleavage was demonstrated. These results suggest that neutralizing mAbs targeting blockade of S1/S2 cleavage are likely to be cross-reactive against various VOCs.


Subject(s)
COVID-19 , Spike Glycoprotein, Coronavirus , Humans , Spike Glycoprotein, Coronavirus/chemistry , Leukocytes, Mononuclear , Antibodies, Viral , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Monoclonal
18.
Sci Rep ; 12(1): 20373, 2022 Nov 27.
Article in English | MEDLINE | ID: covidwho-2133622

ABSTRACT

Immune response induced by COVID-19 vaccine booster against delta and omicron variants was assessed in 65 adults (65-84 years old) early aftesr a first booster dose. An increase in SARS-CoV-2 neutralizing antibodies was shown in individuals not previously infected without evidence of an age-related effect, with lower increase in those infected before a single dose of primary vaccination. Of note, humoral response was observed only starting from the 5th day after the boost.


Subject(s)
COVID-19 , Viral Vaccines , Humans , Aged , Aged, 80 and over , Antibodies, Neutralizing , SARS-CoV-2/genetics , Neutralization Tests , Antibodies, Viral , RNA, Messenger , COVID-19/prevention & control , Vaccination
19.
Nat Commun ; 13(1): 7315, 2022 Nov 28.
Article in English | MEDLINE | ID: covidwho-2133436

ABSTRACT

The COVID-19 course and immunity differ in children and adults. We analyzed immune response dynamics in 28 families up to 12 months after mild or asymptomatic infection. Unlike adults, the initial response is plasmablast-driven in children. Four months after infection, children show an enhanced specific antibody response and lower but detectable spike 1 protein (S1)-specific B and T cell responses than their parents. While specific antibodies decline, neutralizing antibody activity and breadth increase in both groups. The frequencies of S1-specific B and T cell responses remain stable. However, in children, one year after infection, an increase in the S1-specific IgA class switch and the expression of CD27 on S1-specific B cells and T cell maturation are observed. These results, together with the enhanced neutralizing potential and breadth of the specific antibodies, suggest a progressive maturation of the S1-specific immune response. Hence, the immune response in children persists over 12 months but dynamically changes in quality, with progressive neutralizing, breadth, and memory maturation. This implies a benefit for booster vaccination in children to consolidate memory formation.


Subject(s)
COVID-19 , Adult , Child , Humans , SARS-CoV-2 , Antibody Formation , Antibodies, Neutralizing , Immunization, Secondary
20.
Clin Lab Med ; 42(1): 57-73, 2022 03.
Article in English | MEDLINE | ID: covidwho-2130427

ABSTRACT

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.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Antibodies, Viral , Enzyme-Linked Immunosorbent Assay , Humans , Pandemics , Sensitivity and Specificity
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