scholarly journals Polymorphism and Selection Pressure of SARS-CoV-2 Vaccine and Diagnostic Antigens: Implications for Immune Evasion and Serologic Diagnostic Performance

Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 584 ◽  
Author(s):  
Eric Dumonteil ◽  
Claudia Herrera
Keyword(s):  
Test Performance ◽  
Selection Pressure ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Low Frequency ◽  
Genome Sequences ◽  
Serological Tests ◽  
Multiple Regions ◽  
Diagnostic Test Performance ◽  
Protein Conservation

The ongoing SARS-CoV-2 pandemic has triggered multiple efforts for serological tests and vaccine development. Most of these tests and vaccines are based on the Spike glycoprotein (S) or the Nucleocapsid (N) viral protein. Conservation of these antigens among viral strains is critical to ensure optimum diagnostic test performance and broad protective efficacy, respectively. We assessed N and S antigen diversity from 17,853 SARS-CoV-2 genome sequences and evaluated selection pressure. Up to 6–7 incipient phylogenetic clades were identified for both antigens, confirming early variants of the S antigen and identifying new ones. Significant diversifying selection was detected at multiple sites for both antigens. Some sequence variants have already spread in multiple regions, in spite of their low frequency. In conclusion, the N and S antigens of SARS-CoV-2 are well-conserved antigens, but new clades are emerging and may need to be included in future diagnostic and vaccine formulations.

scholarly journals Polymorphism and selection pressure of SARS-CoV-2 vaccine and diagnostic antigens: implications for immune evasion and serologic diagnostic performance

2020 ◽  
Author(s):  
Eric Dumonteil ◽  
Claudia Herrera
Keyword(s):  
Test Performance ◽  
Selection Pressure ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Low Frequency ◽  
Genome Sequences ◽  
Serological Tests ◽  
Multiple Regions ◽  
Diagnostic Test Performance ◽  
Protein Conservation

AbstractThe ongoing SARS-CoV-2 pandemic has triggered multiple efforts for serological tests and vaccine development. Most of these tests and vaccines are based on the Spike glycoprotein (S) or the Nucleocapsid (N) viral protein. Conservation of these antigens among viral strains is critical to ensure optimum diagnostic test performance and broad protective efficacy, respectively. We assessed N and S antigen diversity from 17,853 SARS-CoV-2 genome sequences and evaluated selection pressure. Up to 6-7 incipient phylogenetic clades were identified for both antigens, confirming early variants of the S antigen and identifying new ones. Significant diversifying selection was detected at multiple sites for both antigens. Some sequence variants have already spread in multiple regions, in spite of their low frequency. In conclusion, the N and S antigens of SARS-CoV-2 are well conserved antigens, but new clades are emerging and may need to be included in future diagnostic and vaccine formulations.

scholarly journals Global variation in the SARS-CoV-2 proteome reveals the mutational hotspots in the drug and vaccine candidates

2020 ◽  
Author(s):  
L Ponoop Prasad Patro ◽  
Chakkarai Sathyaseelan ◽  
Patil Pranita Uttamrao ◽  
Thenmalarchelvi Rathinavelan
Keyword(s):  
Nucleocapsid Protein ◽  
Selection Pressure ◽  
Vaccine Development ◽  
Respiratory Syndrome Virus ◽  
Genome Sequences ◽  
Rna Dependent Rna Polymerase ◽  
Positive Selection Pressure ◽  
Vaccine Candidates ◽  
Mutational Hotspots ◽  
Two Phases

ABSTRACTTo accelerate the drug and vaccine development against the severe acute respiratory syndrome virus 2 (SARS-CoV-2), a comparative analysis of SARS-CoV-2 proteome has been performed in two phases by considering manually curated 31389 whole genome sequences from 84 countries. Among the 9 mutations that occur at a high significance (T85I-NPS2, L37F-NSP6, P323L-NSP12, D614G-spike, Q57H-ORF3a, G251V-ORF3a, L84S-ORF8, R203K-nucleocapsid and G204R-nucleocapsid), R203K-nucleocapsid and G204R-nucleocapsid are co-occurring (dependent) mutations and P323L-NSP12 and D614G-spike often appear simultaneously. Other notable variations that appear with a moderate to low significance are, M85-NSP1 deletion, D268-NSP2 deletion, 112 amino acids deletion in ORF8, a phenylalanine insertion amidst F34-F36 (NSP6) and several co-existing (dependent) substitution/deletion (I559V & P585S in NSP2, P504L & Y541C in NSP13, G82 & H83 deletions in NSP1 and K141, S142 & F143 deletions in NSP2) mutations. P323L-NSP12, D614G-spike, L37F-NSP6, L84S-ORF8 and the sequences deficient of the high significant mutations have led to 4 major SARS-CoV-2 clades. The top 5 countries bearing all the high significant and majority of the moderate significant mutations are: USA, England, Wales, Australia and Scotland. Further, the majority of the significant mutations have evolved in the first phase and have already transmitted around the globe indicating the positive selection pressure. Among the 26 SARS-CoV-2 proteins, nucleocapsid protein, ORF3a, ORF8, RNA dependent RNA polymerase and spike exhibit a higher heterogeneity compared with the rest of the proteins. However, NSP9, NSP10, NSP8, the envelope protein and NSP4 are highly resistant to mutations and can be exploited for drug/vaccine development.

scholarly journals Detection of SARS-CoV-2 variants by Abbott molecular, antigen, and serological tests

2021 ◽  
Author(s):  
Mary A Rodgers ◽  
Rahul Batra ◽  
Luke B Snell ◽  
David J Daghfal ◽  
Richard Roth ◽  
...  
Keyword(s):  
Test Performance ◽  
Rapid Test ◽  
Clinical Samples ◽  
Surveillance Program ◽  
Test Device ◽  
Serological Tests ◽  
Virus Variant ◽  
Infectious Dose ◽  
Diagnostic Test Performance ◽  
Tissue Culture Infectious Dose

Background: Viral diversity presents an ongoing challenge for diagnostic tests, which need to accurately detect all circulating variants. The Abbott Global Surveillance program monitors severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants and their impact on diagnostic test performance. Objectives: To evaluate the capacity of Abbott molecular, antigen, and serologic assays to detect the SARS-CoV-2 B.1.1.7, B.1.351 and the P.1 variants. Study design: Virus variant culture stock dilutions (B.1.1.7, BEI NR-54011; B.1.351, BEI NR-54008 and 54009; P.1, BEI NR-54982) and clinical samples from patients with confirmed B.1.1.7 variant infection were run on the Abbott ID NOW COVID-19, m2000 RealTime SARS-CoV-2, Alinity m SARS-CoV-2, and Alinity m Resp-4-Plex molecular assays; the BinaxNOW COVID-19 Ag Card and Panbio COVID-19 Ag Rapid Test Device; and the ARCHITECT/Alinity i SARS-CoV-2 IgG and AdviseDx IgM assays, Panbio COVID-19 IgG assay, and ARCHITECT/Alinity i AdviseDx SARS-CoV-2 IgG II assay. Results: Cultured virus stocks and B.1.1.7 clinical samples were detected with molecular, antigen, and serologic assays in the expected ranges, confirming in silico predictions. The ratio between genome equivalents (GE) and calculated median tissue culture infectious dose (TCID50) were 31- to 83-fold higher for B.1.1.7 cultures compared to B.1.351 and P.1 cultures, demonstrating that GE are more consistent units between cultures than TCID50. Conclusions: Abbott molecular and antigen assays effectively detect B.1.1.7, B.1.351, and P.1 variant infections and Abbott serologic assays detect B.1.1.7 antibodies in patient sera. Future studies with SARS-CoV-2 virus cultures should use quantitative viral load values to compare detection of variants.

scholarly journals Diagnosis of tuberculosis in wildlife: a systematic review

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Jobin Thomas ◽  
Ana Balseiro ◽  
Christian Gortázar ◽  
María A. Risalde
Keyword(s):  
Systematic Review ◽  
Test Performance ◽  
Diagnostic Tests ◽  
Large Scale ◽  
Diagnostic Techniques ◽  
Review Literature ◽  
Meat Industry ◽  
Post Mortem ◽  
Serological Tests ◽  
Ongoing Research

AbstractAnimal tuberculosis (TB) is a multi-host disease caused by members of the Mycobacterium tuberculosis complex (MTC). Due to its impact on economy, sanitary standards of milk and meat industry, public health and conservation, TB control is an actively ongoing research subject. Several wildlife species are involved in the maintenance and transmission of TB, so that new approaches to wildlife TB diagnosis have gained relevance in recent years. Diagnosis is a paramount step for screening, epidemiological investigation, as well as for ensuring the success of control strategies such as vaccination trials. This is the first review that systematically addresses data available for the diagnosis of TB in wildlife following the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The article also gives an overview of the factors related to host, environment, sampling, and diagnostic techniques which can affect test performance. After three screenings, 124 articles were considered for systematic review. Literature indicates that post-mortem examination and culture are useful methods for disease surveillance, but immunological diagnostic tests based on cellular and humoral immune response detection are gaining importance in wildlife TB diagnosis. Among them, serological tests are especially useful in wildlife because they are relatively inexpensive and easy to perform, facilitate large-scale surveillance and can be used both ante- and post-mortem. Currently available studies assessed test performance mostly in cervids, European badgers, wild suids and wild bovids. Research to improve diagnostic tests for wildlife TB diagnosis is still needed in order to reach accurate, rapid and cost-effective diagnostic techniques adequate to a broad range of target species and consistent over space and time to allow proper disease monitoring.

scholarly journals Correlates of SARS-CoV-2 Variants on Deaths, Case Incidence and Case Fatality Ratio among the Continents for the Period of 1 December 2020 to 15 March 2021

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1061
Author(s):  
Wajdy J. Al-Awaida ◽  
Baker Jawabrah Al Hourani ◽  
Samer Swedan ◽  
Refat Nimer ◽  
Foad Alzoughool ◽  
...  
Keyword(s):  
Negative Correlation ◽  
Significant Positive Correlation ◽  
Vaccine Development ◽  
Case Fatality ◽  
Significant Negative Correlation ◽  
Reference Sequence ◽  
Genome Sequences ◽  
Positive Correlation ◽  
Case Fatality Ratio ◽  
Epidemiological Surveys

The outbreak of coronavirus disease 2019 (COVID-19), by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly developed into a worldwide pandemic. Mutations in the SARS-CoV-2 genome may affect various aspects of the disease including fatality ratio. In this study, 553,518 SARS-CoV-2 genome sequences isolated from patients from continents for the period 1 December 2020 to 15 March 2021 were comprehensively analyzed and a total of 82 mutations were identified concerning the reference sequence. In addition, associations between the mutations and the case fatality ratio (CFR), cases per million and deaths per million, were examined. The mutations having the highest frequencies among different continents were Spike_D614G and NSP12_P323L. Among the identified mutations, NSP2_T153M, NSP14_I42V and Spike_L18F mutations showed a positive correlation to CFR. While the NSP13_Y541C, NSP3_T73I and NSP3_Q180H mutations demonstrated a negative correlation to CFR. The Spike_D614G and NSP12_P323L mutations showed a positive correlation to deaths per million. The NSP3_T1198K, NS8_L84S and NSP12_A97V mutations showed a significant negative correlation to deaths per million. The NSP12_P323L and Spike_D614G mutations showed a positive correlation to the number of cases per million. In contrast, NS8_L84S and NSP12_A97V mutations showed a negative correlation to the number of cases per million. In addition, among the identified clades, none showed a significant correlation to CFR. The G, GR, GV, S clades showed a significant positive correlation to deaths per million. The GR and S clades showed a positive correlation to number of cases per million. The clades having the highest frequencies among continents were G, followed by GH and GR. These findings should be taken into consideration during epidemiological surveys of the virus and vaccine development.

scholarly journals 92 Reshaping the Diagnostic Pathways for Investigation of Haematuria During and After The COVID-19 Pandemic: Diagnostic Accuracy of Strategies for Detection of Bladder Cancer from The IDENTIFY Cohort Study

2021 ◽  
Vol 108 (Supplement_2) ◽  
Author(s):  
S Khadhouri ◽  
K Gallagher ◽  
K MacKenzie ◽  
T Shah ◽  
C Gao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cohort Study ◽  
Test Performance ◽  
Bladder Tumour ◽  
Healthcare Services ◽  
Diagnostic Strategies ◽  
Flexible Cystoscopy ◽  
Resource Limited ◽  
Diagnostic Test Performance ◽  
Diagnostic Pathways

Abstract Introduction Diagnostic haematuria services have been reduced due to the COVID-19 pandemic, compromising patient care, and necessitating a more pragmatic pathway. Method The IDENTIFY study was an international, prospective, multicentre cohort study of over 11,000 patients referred to secondary care for investigation of haematuria. Using this data, we developed strategies using combinations of imaging and cytology as triage tests to maximise cancer detection within a pragmatic pathway. Results 8112 patients (74·4%) received an ultrasound or a CT urogram, with or without cytology. 5737 (70·7%) patients had visible haematuria (VH) and 2375 (29·3%) had non-visible haematuria (NVH). Diagnostic test performance was used to determine optimal age cut-offs for four proposed strategies. We recommended proceeding directly to transurethral resection of bladder tumour for patients of any age with positive triage tests for cancer. Patients with negative triage tests under 35-years-old with VH, or under 50-years-old with NVH can safely be discharged without undergoing flexible cystoscopy. The remaining patients may undergo flexible cystoscopy, with a greater priority for older patients to capture high risk bladder cancer. Conclusions We suggest diagnostic strategies in patients with haematuria, which focus on detection of bladder cancer, whilst reducing the burden to healthcare services in a resource-limited setting.

Design of the Recombinant Influenza Neuraminidase Antigen is Crucial for its Biochemical Properties and Protective Efficacy

2021 ◽  
Author(s):  
Jin Gao ◽  
Laura Klenow ◽  
Lisa Parsons ◽  
Tahir Malik ◽  
Je-Nie Phue ◽  
...  
Keyword(s):  
Single Dose ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Biochemical Properties ◽  
Cell System ◽  
Influenza Vaccines ◽  
H1n1 Vaccine ◽  
Protective Properties ◽  
Head Domain ◽  
Tetramerization Domain

Supplementing influenza vaccines with recombinant neuraminidase (rNA) antigens remains a promising approach for improving the suboptimal vaccine efficacy. However, correlations among rNA designs, properties, and protection have not been systematically investigated. Here, we performed a comparative analysis of several rNAs produced using the baculovirus/insect cell system. The rNAs were designed with different tetramerization motifs and NA domains from a recent H1N1 vaccine strain (A/Brisbane/02/2018) and were compared for enzymatic property, antigenicity, stability, and protection in mice. We found that distinct enzymatic properties are associated with rNAs containing the NA head-domain versus the full-ectodomain, formation of higher order rNA oligomers is tetramerization domain-dependent, whereas protective efficacy is more contingent on the combination of the tetramerization and NA domains. Following single-dose immunizations, a rNA possessing the full-ectodomain and the tetramerization motif from the human vasodilator-stimulated phosphoprotein provided much better protection than a rNA with ∼10-fold more enzymatically active molecules that is comprised of the head-domain and the same tetramerization motif. In contrast, these two rNA designs provided comparable protection when the tetramerization motif from the tetrabrachion protein was used instead. These findings demonstrate that individual rNAs should be thoroughly evaluated for vaccine development, as the heterologous domain combination can result in rNAs with similar key attributes but vastly differ in protection. IMPORTANCE For several decades it has been proposed that influenza vaccines could be supplemented with recombinant neuraminidase (rNA) to improve the efficacy. However, some key questions for manufacturing stable and immunogenic rNA remain to be answered. We show here that the tetramerization motifs and NA domains included in the rNA construct design can have a profound impact on the biochemical, immunogenic and protective properties. We also show that the single-dose immunization regimen is more informative for assessing the rNA immune response and protective efficacy, which is surprisingly more dependent on the specific combination of NA and tetramerization domains than common attributes for evaluating NA. Our findings may help to optimize the design of rNAs that can be used to improve or develop influenza vaccines.

Sign in / Sign up

Export Citation Format

Share Document