scholarly journals Diagnostics and spread of SARS-CoV-2 in Western Africa: An observational laboratory-based study from Benin

2020 ◽  
Author(s):  
Anges Yadouleton ◽  
Anna-Lena Sander ◽  
Andres Moreira-Soto ◽  
Carine Tchibozo ◽  
Gildas Hounkanrin ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Fold Increase ◽  
Epidemiological Studies ◽  
Antibody Responses ◽  
Surveillance Systems ◽  
Rt Pcr ◽  
African Countries ◽  
Western Africa ◽  
Public Data ◽  
Diagnostic Capacity

AbstractInformation on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spread in Africa is limited by fragile surveillance systems and insufficient diagnostic capacity.We assessed the coronavirus disease-19 (COVID-19)-related diagnostic workload in Benin, Western Africa, characterized SARS-CoV-2 genomes from 12 acute cases of COVID-19, used those together with public data to estimate SARS-CoV-2 transmission dynamics in a Bayesian framework, validated a widely used diagnostic dual target RT-PCR kit donated to African countries, and conducted serological analyses in 68 sera from confirmed COVID-19 cases and from febrile patients sampled before the predicted SARS-CoV-2 introduction.We found a 15-fold increase in the monthly laboratory workload due to COVID-19. Genomic surveillance showed introductions of three distinct SARS-CoV-2 lineages. SARS-CoV-2 genome-based analyses yielded an R0 estimate of 4.4 (95% confidence interval: 2.0-7.7), suggesting intense spread of SARS-CoV-2 in Africa. RT-PCR-based tests were highly sensitive but showed variation of internal controls and between diagnostic targets. Commercially available SARS-CoV-2 ELISAs showed up to 25% false-positive results depending on antigen and antibody types, likely due to unspecific antibody responses elicited by acute malaria according to lack of SARS-CoV-2-specific neutralizing antibody responses and relatively higher parasitemia in those sera.We confirm an overload of the diagnostic capacity in Benin and provide baseline information on the usability of genome-based surveillance in resource-limited settings. Sero-epidemiological studies needed to assess SARS-CoV-2 spread may be put at stake by low specificity of tests in tropical settings globally. The increasing diagnostic challenges demand continuous support of national and supranational African stakeholders.FundingThis work was supported by the Deutsche Gesellschaft für Internationale Zusammenarbeit (GIZ) GmbH.

scholarly journals Conformational diversity facilitates antibody mutation trajectories and discrimination between foreign and self-antigens

2020 ◽  
Vol 117 (36) ◽  
pp. 22341-22350 ◽  
Author(s):  
Deborah L. Burnett ◽  
Peter Schofield ◽  
David B. Langley ◽  
Jennifer Jackson ◽  
Katherine Bourne ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Fold Increase ◽  
Cross Reactivity ◽  
Antibody Responses ◽  
X Ray ◽  
X Ray Crystallography ◽  
Conformational Diversity ◽  
High Discrimination ◽  
Complementarity Determining Regions ◽  
Self Antigen

Conformational diversity and self-cross-reactivity of antigens have been correlated with evasion from neutralizing antibody responses. We utilized single cell B cell sequencing, biolayer interferometry and X-ray crystallography to trace mutation selection pathways where the antibody response must resolve cross-reactivity between foreign and self-proteins bearing near-identical contact surfaces, but differing in conformational flexibility. Recurring antibody mutation trajectories mediate long-range rearrangements of framework (FW) and complementarity determining regions (CDRs) that increase binding site conformational diversity. These antibody mutations decrease affinity for self-antigen 19-fold and increase foreign affinity 67-fold, to yield a more than 1,250-fold increase in binding discrimination. These results demonstrate how conformational diversity in antigen and antibody does not act as a barrier, as previously suggested, but rather facilitates high affinity and high discrimination between foreign and self.

scholarly journals Glycosylation of Immunodominant Linear Epitopes in the Carboxy-Terminal Region of the Caprine Arthritis-Encephalitis Virus Surface Envelope Enhances Vaccine-Induced Type-Specific and Cross-Reactive Neutralizing Antibody Responses

2004 ◽  
Vol 78 (17) ◽  
pp. 9190-9202 ◽  
Author(s):  
J. D. Trujillo ◽  
N. M. Kumpula-McWhirter ◽  
K. J. Hötzel ◽  
M. Gonzalez ◽  
W. P. Cheevers
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Fold Increase ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Type ◽  
Virus Surface ◽  
Antibody Titers ◽  
Linear Epitopes ◽  
Carboxy Terminal

ABSTRACT This study evaluated type-specific and cross-reactive neutralizing antibodies induced by immunization with modified surface glycoproteins (SU) of the 63 isolate of caprine arthritis-encephalitis lentivirus (CAEV-63). Epitope mapping of sera from CAEV-infected goats localized immunodominant linear epitopes in the carboxy terminus of SU. Two modified SU (SU-M and SU-T) and wild-type CAEV-63 SU (SU-W) were produced in vaccinia virus and utilized to evaluate the effects of glycosylation or the deletion of immunodominant linear epitopes on neutralizing antibody responses induced by immunization. SU-M contained two N-linked glycosylation sites inserted into the target epitopes by R539S and E542N mutations. SU-T was truncated at 518A, upstream from the target epitopes, by introduction of termination codons at 519Y and 521Y. Six yearling Saanen goats were immunized subcutaneously with 30 μg of SU-W, SU-M, or SU-T in Quil A adjuvant and boosted at 3, 7, and 16 weeks. SU antibody titers determined by indirect enzyme-linked immunosorbent assay demonstrated anamnestic responses after each boost. Wild-type and modified SU-induced type-specific CAEV-63 neutralizing antibodies and cross-reactive neutralizing antibodies against CAEV-Co, a virus isolate closely related to CAEV-63, and CAEV-1g5, an isolate geographically distinct from CAEV-63, were determined. Immunization with SU-T resulted in altered recognition of SU linear epitopes and a 2.8- to 4.6-fold decrease in neutralizing antibody titers against CAEV-63, CAEV-Co, and CAEV-1g5 compared to titers of SU-W-immunized goats. In contrast, immunization with SU-M resulted in reduced recognition of glycosylated epitopes and a 2.4- to 2.7-fold increase in neutralizing antibody titers compared to titers of SU-W-immunized goats. Thus, the glycosylation of linear immunodominant nonneutralization epitopes, but not epitope deletion, is an effective strategy to enhance neutralizing antibody responses by immunization.

scholarly journals Neutralizing antibody titres in SARS-CoV-2 infections

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eric H. Y. Lau ◽  
Owen T. Y. Tsang ◽  
David S. C. Hui ◽  
Mike Y. W. Kwan ◽  
Wai-hung Chan ◽  
...  
Keyword(s):  
Severe Disease ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Global Public Health ◽  
Rt Pcr ◽  
Asymptomatic Patients ◽  
Antibody Titres ◽  
Observational Cohort ◽  
Public Health Challenge ◽  
Asymptomatic Infections

AbstractThe SARS-CoV-2 pandemic poses the greatest global public health challenge in a century. Neutralizing antibody is a correlate of protection and data on kinetics of virus neutralizing antibody responses are needed. We tested 293 sera from an observational cohort of 195 reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections collected from 0 to 209 days after onset of symptoms. Of 115 sera collected ≥61 days after onset of illness tested using plaque reduction neutralization (PRNT) assays, 99.1% remained seropositive for both 90% (PRNT90) and 50% (PRNT50) neutralization endpoints. We estimate that it takes at least 372, 416 and 133 days for PRNT50 titres to drop to the detection limit of a titre of 1:10 for severe, mild and asymptomatic patients, respectively. At day 90 after onset of symptoms (or initial RT-PCR detection in asymptomatic infections), it took 69, 87 and 31 days for PRNT50 antibody titres to decrease by half (T1/2) in severe, mild and asymptomatic infections, respectively. Patients with severe disease had higher peak PRNT90 and PRNT50 antibody titres than patients with mild or asymptomatic infections. Age did not appear to compromise antibody responses, even after accounting for severity. We conclude that SARS-CoV-2 infection elicits robust neutralizing antibody titres in most individuals.

scholarly journals Protection against SARS-CoV-2 Beta Variant in mRNA-1273 Boosted Nonhuman Primates

2021 ◽  
Author(s):  
Kizzmekia S. Corbett ◽  
Matthew Gagne ◽  
Danielle Wagner ◽  
Sarah O'Connell ◽  
Sandeep R. Narpala ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Geometric Mean ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Fold Increase ◽  
Primary Response ◽  
Antibody Responses ◽  
Lower Airway ◽  
Memory Time ◽  
High Level

Neutralizing antibody responses gradually wane after vaccination with mRNA-1273 against several variants of concern (VOC), and additional boost vaccinations may be required to sustain immunity and protection. Here, we evaluated the immune responses in nonhuman primates that received 100 μg of mRNA-1273 vaccine at 0 and 4 weeks and were boosted at week 29 with mRNA-1273 (homologous) or mRNA-1273.β (heterologous), which encompasses the spike sequence of the B.1.351 (beta or β) variant. Reciprocal ID50 pseudovirus neutralizing antibody geometric mean titers (GMT) against live SARS-CoV-2 D614G and the β variant, were 4700 and 765, respectively, at week 6, the peak of primary response, and 644 and 553, respectively, at a 5-month post-vaccination memory time point. Two weeks following homologous or heterologous boost β-specific reciprocal ID50 GMT were 5000 and 3000, respectively. At week 38, animals were challenged in the upper and lower airway with the β variant. Two days post-challenge, viral replication was low to undetectable in both BAL and nasal swabs in most of the boosted animals. These data show that boosting with the homologous mRNA-1273 vaccine six months after primary immunization provides up to a 20-fold increase in neutralizing antibody responses across all VOC, which may be required to sustain high-level protection against severe disease, especially for at-risk populations.

scholarly journals An Observational Laboratory-Based Assessment of SARS-CoV-2 Molecular Diagnostics in Benin, Western Africa

mSphere ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Anna-Lena Sander ◽  
Anges Yadouleton ◽  
Andres Moreira-Soto ◽  
Carine Tchibozo ◽  
Gildas Hounkanrin ◽  
...  
Keyword(s):  
Genomic Diversity ◽  
Clinical Samples ◽  
Central Laboratory ◽  
Rt Pcr ◽  
Target Domain ◽  
African Countries ◽  
Protein Variant ◽  
Clinical Sensitivity ◽  
Western Africa

ABSTRACT Information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread in Africa is limited by insufficient diagnostic capacity. Here, we assessed the coronavirus disease (COVID-19)-related diagnostic workload during the onset of the pandemic in the central laboratory of Benin, Western Africa; characterized 12 SARS-CoV-2 genomes from returning travelers; and validated the Da An RT-PCR-based diagnostic kit that is widely used across Africa. We found a 15-fold increase in the monthly laboratory workload due to COVID-19, dealt with at the cost of routine activities. Genomic surveillance showed near-simultaneous introduction of distinct SARS-CoV-2 lineages termed A.4 and B.1, including the D614G spike protein variant potentially associated with higher transmissibility from travelers from six different European and African countries during March-April 2020. We decoded the target regions within the ORF1ab and N genes of the Da An dual-target kit by MinION-based amplicon sequencing. Despite relatively high similarity between SARS-CoV-2 and endemic human coronaviruses (HCoVs) within the ORF1ab target domain, no cross-detection of high-titered cell culture supernatants of HCoVs was observed, suggesting high analytical specificity. The Da An kit was highly sensitive, detecting 3.2 to 9.0 copies of target-specific in vitro transcripts/reaction. Although discrepant test results were observed in low-titered clinical samples, clinical sensitivity of the Da An kit was at least comparable to that of commercial kits from affluent settings. In sum, virologic diagnostics are achievable in a resource-limited setting, but unprecedented pressure resulting from COVID-19-related diagnostics requires rapid and sustainable support of national and supranational stakeholders addressing limited laboratory capacity. IMPORTANCE Months after the start of the COVID-19 pandemic, case numbers from Africa are surprisingly low, potentially because the number of SARS-CoV-2 tests performed in Africa is lower than in other regions. Here, we show an overload of COVID-19-related diagnostics in the central laboratory of Benin, Western Africa, with a stagnating average number of positive samples irrespective of daily sample counts. SARS-CoV-2 genomic surveillance confirmed a high genomic diversity in Benin introduced by travelers returning from Europe and other African countries, including early circulation of the D614G spike mutation associated with potentially higher transmissibility. We validated a widely used RT-PCR kit donated by the Chinese Jack Ma Foundation and confirmed high analytical specificity and clinical sensitivity equivalent to tests used in affluent settings. Our assessment shows that although achievable in an African setting, the burden from COVID-19-related diagnostics on national reference laboratories is very high.

scholarly journals 453. Neutralizing Antibody Responses to SARS-CoV-2 in Professional Soccer Players

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S327-S328
Author(s):  
Jorge Pagura ◽  
Clovis Arns de Cunha ◽  
Roberto Nishimura ◽  
Sergio Wey ◽  
André Pedrinelli ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Test ◽  
Antibody Responses ◽  
Soccer Players ◽  
P Value ◽  
Rt Pcr ◽  
Professional Soccer ◽  
Antibody Levels ◽  
Pcr Test

Abstract Background The Brazilian Football Confederation (CBF) protocol to control the spread of COVID-19 among professional soccer players is based on four cornerstone measures: (1) Tracing all symptomatic and asymptomatic COVID-19 cases by clinical monitoring and nasal swab SARS-CoV-2 RT-PCR testing up to 3 days before the soccer games; (2) Respiratory isolation of all SARS-CoV-2 positive players for at least 10 days, regardless symptoms; (3) All player with clinical suspicion of COVID-19 were immediately quarantined; (4) If a player became SARS-CoV-2 positive after the game, the other players were allowed to play the next game, if they remained asymptomatic and SARS-CoV-2 RT-PCR negative. Understanding how antibody responses to SARS-CoV-2 evolve can provide insights into therapeutic and testing approaches for COVID-19. In the present study we profile the antibody responses of players up to nine months from a SARS-CoV-2 positive RT-PCR test. Methods Serum samples were obtained from 955 soccer players, and analyzed at the same laboratory in São Paulo city, in the Hospital Israelita Albert Einstein. It was used the cPas Technology, the sVNT kit for detecting and measuring circulating neutralizing antibodies against the SARS-CoV-2 virus. Results Neutralizing antibody was positive for 416 samples (416/955=44%; C.I. 95%= [40%; 47%]). From the 955 soccer players, 454 had RT-PCR+ previously, up to nine months until the neutralizing antibody tests. From this 454 players, 172 (38%) had neutralizing antibody below 20% (C.I. 95% = [34%; 42%]), 30 (7%) between 20% and 30% (C.I. 95% = [5%; 9%]), and e 252 (56%) above 30% (C.I. 95% =[51%; 60%]). Antibody responses to SARS-CoV-2 were significantly higher in individuals RT-PCR+ (Table 1). There was no difference between the neutralizing antibody responses status to SARS-CoV-2 and the time between the RT-PCR+ and the neutralizing antibody test (p-value = 0.423; Figures 1 and 2, Table 2). Table 1. Neutralizing antibody responses to SARS-CoV-2. Figure 1. Scatter plot with Time between RT-PCR+ and neutralizing antibody (days) versus Neutralizing antibody levels. Table 2. Time between RT-PCR+ and neutralizing antibody (days) versus Neutralizing antibody levels. Conclusion This study found neutralizing activity of infection against SARS-CoV-2 in 63% RT-PCR+ individuals, but only in 26% in RT-PCR(-) players. Level of neutralizing antibody responses maintained stable until up to nine months after a RT-PCR+. Figure 2. Percentage of soccer players at each antibody level (below 20%, between 20% and 30%, and above 30%) versus time between the positive RT-PCR test and neutralizing antibody test (days). Disclosures All Authors: No reported disclosures

Crowdsourcing Covid-19 signals in sub-Saharan Africa: Leveraging digital contributor networks for participatory surveillance of Covid-19 symptoms and deaths (Preprint)

2020 ◽  
Author(s):  
Ngozi A Erondu ◽  
Sagal A Ali ◽  
Mohamed Ali ◽  
Schadrac C Agbla
Keyword(s):  
Public Health ◽  
Sub Saharan Africa ◽  
Specific Information ◽  
Surveillance Systems ◽  
Health Seeking ◽  
African Countries ◽  
Cross Sectional Survey ◽  
Local Networks ◽  
The World ◽  
Sub Saharan

BACKGROUND In sub-Saharan Africa, underreporting of cases and deaths has been attributed to various factors including, weak disease surveillance, low health-seeking behaviour of flu like symptoms, and stigma of Covid-19. There is evidence that SARS-CoV-2 spread mimics transmission patterns of other countries across the world. Since the Covid-19 pandemic has changed the way research can be conducted and in light of restrictions on travel and risks to in-person data collection, innovative approaches to collecting data must be considered. Nearly 50% of Africa’s population is a unique mobile subscriber and it is one of the fastest growing smart-phone marketplaces in the world; hence, mobile phone platforms should be considered to monitor Covid-19 trends in the community. OBJECTIVE We demonstrate the use of digital contributor platforms to survey individuals about cases of flu-like symptoms and instances of unexplained deaths in Ethiopia, Kenya, Nigeria, Somalia, and Zimbabwe. METHODS Rapid cross-sectional survey of individuals with severe flu and pneumonia symptoms and unexplained deaths in Ethiopia, Kenya, Nigeria, Somalia and Zimbabwe RESULTS Using a non-health specific information platform, we found COVID-19 signals in five African countries, specifically: •Across countries, nearly half of the respondents (n=739) knew someone who had severe flu or pneumonia symptoms in recent months. •One in three respondents from Somalia and one in five from Zimbabwe respondents said they knew more than five people recently displaying flu and/or pneumonia symptoms. •In Somalia there were signals that a large number of people might be dying outside of health facilities, specifically in their homes or in IDP or refugee camps. CONCLUSIONS Existing digital contributor platforms with local networks are a non-traditional data source that can provide information from the community to supplement traditional government surveillance systems and academic surveys. We demonstrate that using these distributor networks to for community surveys can provide periodic information on rumours but could also be used to capture local sentiment to inform public health decision-making; for example, these insights could be useful to inform strategies to increase confidence in Covid19 vaccine. As Covid-19 continues to spread somewhat silently across sub-Saharan Africa, regional and national public health entities should consider expanding event-based surveillance sources to include these systems.

scholarly journals Bacteremia Among Febrile Patients Attending Selected Healthcare Facilities in Ibadan, Nigeria

2019 ◽  
Vol 69 (Supplement_6) ◽  
pp. S466-S473 ◽  
Author(s):  
Oluwafemi Popoola ◽  
Aderemi Kehinde ◽  
Veronica Ogunleye ◽  
Oluwafemi J Adewusi ◽  
Trevor Toy ◽  
...  
Keyword(s):  
Antimicrobial Susceptibility ◽  
Bacterial Infections ◽  
Common Species ◽  
Epidemiological Studies ◽  
Multidrug Resistant ◽  
African Countries ◽  
Healthcare Facilities ◽  
Relative Contribution ◽  
Polymerase Chain ◽  
Ibadan Nigeria

Abstract Background The relative contribution of bacterial infections to febrile disease is poorly understood in many African countries due to diagnostic limitations. This study screened pediatric and adult patients attending 4 healthcare facilities in Ibadan, Nigeria, for bacteremia and malaria parasitemia. Methods Febrile patients underwent clinical diagnosis, malaria parasite testing, and blood culture. Bacteria from positive blood cultures were isolated and speciated using biochemical and serological methods, and Salmonella subtyping was performed by polymerase chain reaction. Antimicrobial susceptibility was tested by disk diffusion. Results A total of 682 patients were recruited between 16 June and 16 October 2017; 467 (68.5%) were <18 years of age. Bacterial pathogens were cultured from the blood of 117 (17.2%) patients, with Staphylococcus aureus (69 [59.0%]) and Salmonella enterica (34 [29.1%]) being the most common species recovered. Twenty-seven (79.4%) of the Salmonella isolates were serovar Typhi and the other 7 belonged to nontyphoidal Salmonella serovarieties. Thirty-four individuals were found to be coinfected with Plasmodium falciparum and bacteria. Five (14.7%) of these coinfections were with Salmonella, all in children aged <5 years. Antimicrobial susceptibility testing revealed that most of the Salmonella and Staphylococcus isolates were multidrug resistant. Conclusions The study demonstrates that bacteria were commonly recovered from febrile patients with or without malaria in this location. Focused and extended epidemiological studies are needed for the introduction of typhoid conjugate vaccines that have the potential to prevent a major cause of severe community-acquired febrile diseases in our locality.

scholarly journals A Single Immunization with Spike-Functionalized Ferritin Vaccines Elicits Neutralizing Antibody Responses against SARS-CoV-2 in Mice

2021 ◽  
Author(s):  
Abigail E. Powell ◽  
Kaiming Zhang ◽  
Mrinmoy Sanyal ◽  
Shaogeng Tang ◽  
Payton A. Weidenbacher ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses
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