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1.
Frontiers in medicine ; 9, 2022.
Article in English | EuropePMC | ID: covidwho-1877431

ABSTRACT

Background Currently, promoted vaccinations against SARS-CoV-2 are being given out globally. However, the occurrence of numerous COVID-19 variants has hindered the goal of rapid mitigation of the COVID-19 pandemic by effective mass vaccinations. The real-word effectiveness of the current vaccines against COVID-19 variants has not been assessed by published reviews. Therefore, our study evaluated the overall effectiveness of current vaccines and the differences between the various vaccines and variants. Methods PubMed, Embase, Cochrane Library, medRxiv, bioRxiv, and arXiv were searched to screen the eligible studies. The Newcastle–Ottawa scale and the Egger test were applied to estimate the quality of the literature and any publication bias, respectively. The pooled incident rates of different variants after vaccination were estimated by single-arm analysis. Meanwhile, the pooled efficacies of various vaccines against variants were evaluated by two-arm analysis using odds ratios (ORs) and vaccine effectiveness (VE). Results A total of 6,118 studies were identified initially and 44 articles were included. We found that the overall incidence of variants post first/second vaccine were 0.07 and 0.03, respectively. The VE of the incidence of variants post first vaccine between the vaccine and the placebo or unvaccinated population was 40% and post second vaccine was 96%, respectively. The sub-single-arm analysis showed a low prevalence rate of COVID-19 variants after specific vaccination with the pooled incidence below 0.10 in most subgroups. Meanwhile, the sub-two-arm analysis indicated that most current vaccines had a good or moderate preventive effect on certain variants considering that the VE in these subgroups was between 66 and 95%, which was broadly in line with the results of the sub-single-arm analysis. Conclusion Our meta-analysis shows that the current vaccines that are used globally could prevent COVID-19 infection and restrict the spread of variants to a great extent. We would also support maximizing vaccine uptake with two doses, as the effectiveness of which was more marked compared with one dose. Although the mRNA vaccine was the most effective against variants according to our study, specific vaccines should be taken into account based on the local dominant prevalence of variants.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308922

ABSTRACT

COVID-19 has spread worldwide. However, SARS-CoV-2 serological markers, which usually important indicators of disease progression, remains to be studied. To determine serological patterns during infection and their corresponding influencing factors, we conducted a cohort study including 115 patients with COVID-19 from 41 hospitals. The study included measuring IgM, IgG, and neutralizing antibodies (NAb) in serum, conducting epidemiological survey of the subjects, and retrieving clinical indicators from electronic medical records. We found NAb had the highest seroconversion rate (79.61%), followed by IgG (60.42%), and IgM (26.56%). Seroconversion rate peaked 20–40 d post-infection with NAb reaching 100%. The Geometric mean of NAb ID 50 is 201 (30 to 6271). The NAb titer was positively correlated with duration of infection (p = 0), IgM (p = 0.016), and IgG (p = 0). Compared with IgM or IgG, NAb has better diagnostic sensitivity and serological patterns are valuable for clinical diagnosis and disease monitoring.

4.
Cell Res ; 32(3): 269-287, 2022 03.
Article in English | MEDLINE | ID: covidwho-1634806

ABSTRACT

The emergence of SARS-CoV-2 variants and potentially other highly pathogenic sarbecoviruses in the future highlights the need for pan-sarbecovirus vaccines. Here, we discovered a new STING agonist, CF501, and found that CF501-adjuvanted RBD-Fc vaccine (CF501/RBD-Fc) elicited significantly stronger neutralizing antibody (nAb) and T cell responses than Alum- and cGAMP-adjuvanted RBD-Fc in mice. Vaccination of rabbits and rhesus macaques (nonhuman primates, NHPs) with CF501/RBD-Fc elicited exceptionally potent nAb responses against SARS-CoV-2 and its nine variants and 41 S-mutants, SARS-CoV and bat SARSr-CoVs. CF501/RBD-Fc-immunized hACE2-transgenic mice were almost completely protected against SARS-CoV-2 challenge, even 6 months after the initial immunization. NHPs immunized with a single dose of CF501/RBD-Fc produced high titers of nAbs. The immunized macaques also exhibited durable humoral and cellular immune responses and showed remarkably reduced viral load in the upper and lower airways upon SARS-CoV-2 challenge even at 108 days post the final immunization. Thus, CF501/RBD-Fc can be further developed as a novel pan-sarbecovirus vaccine to combat current and future outbreaks of sarbecovirus diseases.


Subject(s)
COVID-19 , Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Macaca mulatta , Mice , Rabbits , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , T-Lymphocytes
5.
Emerg Microbes Infect ; 11(1): 18-29, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1532383

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 variants have continued to emerge in diverse geographic locations with a temporal distribution. The Lambda variant containing multiple mutations in the spike protein, has thus far appeared mainly in South America. The variant harbours two mutations in the receptor binding domain, L452Q and F490S, which may change its infectivity and antigenicity to neutralizing antibodies. In this study, we constructed 10 pseudoviruses to study the Lambda variant and each individual amino acid mutation's effect on viral function, and used eight cell lines to study variant infectivity. In total, 12 monoclonal antibodies, 14 convalescent sera, and 23 immunized sera induced by mRNA vaccines, inactivated vaccine, and adenovirus type 5 vector vaccine were used to study the antigenicity of the Lambda variant. We found that compared with the D614G reference strain, Lambda demonstrated enhanced infectivity of Calu-3 and LLC-MK2 cells by 3.3-fold and 1.6-fold, respectively. Notably, the sensitivity of the Lambda variant to 5 of 12 neutralizing monoclonal antibodies, 9G11, AM180, R126, X593, and AbG3, was substantially diminished. Furthermore, convalescent- and vaccine-immunized sera showed on average 1.3-2.5-fold lower neutralizing titres against the Lambda variant. Single mutation analysis revealed that this reduction in neutralization was caused by L452Q and F490S mutations. Collectively, the reduced neutralization ability of the Lambda variant suggests that the efficacy of monoclonal antibodies and vaccines may be compromised during the current pandemic.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Antibodies, Monoclonal/chemistry , Antibodies, Neutralizing/chemistry , Binding Sites , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Cell Line , Host-Pathogen Interactions , Humans , Immune Sera , Models, Molecular , Mutation , Neutralization Tests , Protein Binding , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Structure-Activity Relationship
6.
Signal Transduct Target Ther ; 6(1): 346, 2021 09 24.
Article in English | MEDLINE | ID: covidwho-1437668

ABSTRACT

Antibody-dependent cellular cytotoxicity (ADCC) responses to viral infection are a form of antibody regulated immune responses mediated through the Fc fragment. Whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered ADCC responses contributes to COVID-19 disease development is currently not well understood. To understand the potential correlation between ADCC responses and COVID-19 disease development, we analyzed the ADCC activity and neutralizing antibody response in 255 individuals ranging from asymptomatic to fatal infections over 1 year post disease. ADCC was elicited by 10 days post-infection, peaked by 11-20 days, and remained detectable until 400 days post-infection. In general, patients with severe disease had higher ADCC activities. Notably, patients who had severe disease and recovered had higher ADCC activities than patients who had severe disease and deceased. Importantly, ADCC activities were mediated by a diversity of epitopes in SARS-COV-2-infected mice and induced to comparable levels against SARS-CoV-2 variants of concern (VOCs) (B.1.1.7, B.1.351, and P.1) as that against the D614G mutant in human patients and vaccinated mice. Our study indicates anti-SARS-CoV-2 ADCC as a major trait of COVID-19 patients with various conditions, which can be applied to estimate the extra-neutralization level against COVID-19, especially lethal COVID-19.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antibody-Dependent Cell Cytotoxicity , COVID-19/immunology , SARS-CoV-2/immunology , Adult , Aged , Animals , Cell Line, Tumor , Female , Humans , Male , Mice , Middle Aged
7.
Vaccine ; 39(41): 6050-6056, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1386708

ABSTRACT

The development of an effective vaccine to control the global coronavirus disease-2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus- 2 (SARS-CoV-2) is of utmost importance. In this study, a synthetic DNA-based vaccine candidate, known as pSV10-SARS-CoV-2, expressing the SARS-CoV-2 spike protein was designed and tested in 39 BALB/c mice with BC01, an adjuvant derived from unmethylated CpG motif-containing DNA fragments from the Bacillus Calmette-Guerin genome. Mice vaccinated with pSV10-SARS-CoV-2 with BC01 produced early neutralizing antibodies and developed stronger humoral and cellular immune responses compared to mice that received the DNA vaccine only. Moreover, sera from mice vaccinated with pSV10-SARS-CoV-2 with BC01 can neutralize certain variants, including 614G, 614G + 472 V, 452R, 483A, 501Y.V2, and B.1.1.7. The results of this study demonstrate that the addition of BC01 to a DNA-vaccine for COVID-19 could elicit more effective neutralizing antibody titers for disease prevention.


Subject(s)
COVID-19 , Vaccines, DNA , Animals , Antibodies, Neutralizing , Antibodies, Viral , BCG Vaccine , COVID-19 Vaccines , DNA , Genomics , Humans , Immunity, Cellular , Mice , Mice, Inbred BALB C , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
8.
Cell Discov ; 7(1): 53, 2021 Jul 20.
Article in English | MEDLINE | ID: covidwho-1319024

ABSTRACT

Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 3.8 million deaths to date. Neutralizing antibodies are effective therapeutic measures. However, many naturally occurring mutations at the receptor-binding domain (RBD) have emerged, and some of them can evade existing neutralizing antibodies. Here, we utilized RenMab, a novel mouse carrying the entire human antibody variable region, for neutralizing antibody discovery. We obtained several potent RBD-blocking antibodies and categorized them into four distinct groups by epitope mapping. We determined the involved residues of the epitope of three representative antibodies by cryo-electron microscopy (Cryo-EM) studies. Moreover, we performed neutralizing experiments with 50 variant strains with single or combined mutations and found that the mixing of three epitope-distinct antibodies almost eliminated the mutant escape. Our study provides a sound basis for the rational design of fully human antibody cocktails against SARS-CoV-2 and pre-emergent coronaviral threats.

9.
Virol Sin ; 36(5): 934-947, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1293454

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high-affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446-S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351, and reacted with mutations of N501Y, E484K, and L452R, indicated that it may also neutralize the recent India endemic strain B.1.617. The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants, which mitigated the risk of viral escape. Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-CoV-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-CoV-2 variants.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Neutralizing , Humans , Spike Glycoprotein, Coronavirus
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