scholarly journals Calibration of two validated SARS-CoV-2 pseudovirus neutralization assays for COVID-19 vaccine evaluation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yunda Huang ◽  
Oleg Borisov ◽  
Jia Jin Kee ◽  
Lindsay N. Carpp ◽  
Terri Wrin ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
World Health ◽  
United States Government ◽  
Phase 3 ◽  
Efficacy Trials ◽  
Combining Data ◽  
The World ◽  
States Government ◽  
Common Scale ◽  
Aid Decision

AbstractVaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudovirus-based SARS-CoV-2 neutralization assays, with each trial using one of the two assays. Here we describe and compare the nAb titers obtained in the two assays. We observe that one assay consistently yielded higher nAb titers than the other when both assays were performed on the World Health Organization’s anti-SARS-CoV-2 immunoglobulin International Standard, COVID-19 convalescent sera, and mRNA-1273 vaccinee sera. To overcome the challenge this difference in readout poses in comparing/combining data from the two assays, we evaluate three calibration approaches and show that readouts from the two assays can be calibrated to a common scale. These results may aid decision-making based on data from these assays for the evaluation and licensure of new or adapted COVID-19 vaccines.

scholarly journals Calibration of Two Validated SARS-CoV-2 Pseudovirus Neutralization Assays for COVID-19 Vaccine Evaluation

2021 ◽  
Author(s):  
Yunda Huang ◽  
Oleg Borisov ◽  
Jia Jin Kee ◽  
Lindsay Carpp ◽  
Terri Wrin ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
World Health ◽  
United States Government ◽  
Phase 3 ◽  
Efficacy Trials ◽  
Combining Data ◽  
The World ◽  
States Government ◽  
Common Scale ◽  
Aid Decision

Abstract Vaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States Government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudovirus-based SARS-CoV-2 neutralization assays, with each trial using one of the two assays. Here we describe and compare the nAb titers obtained in the two assays. We observe that one assay consistently yielded higher nAb titers than the other when both assays were performed on the World Health Organization’s anti-SARS-CoV-2 immunoglobulin International Standard, COVID-19 convalescent sera, and mRNA-1273 vaccinee sera. To overcome the challenge this difference in readout poses in comparing/combining data from the two assays, we evaluate three calibration approaches and show that readouts from the two assays can be calibrated to a common scale. These results may aid decision-making based on data from these assays for the evaluation and licensure of new or adapted COVID-19 vaccines.

scholarly journals Calibration of Two Validated SARS-CoV-2 Pseudovirus Neutralization Assays for COVID-19 Vaccine Evaluation

2021 ◽  
Author(s):  
Yunda Huang ◽  
Oleg Borisov ◽  
Jia Jin Kee ◽  
Lindsay N. Carpp ◽  
Terri Wrin ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
World Health ◽  
United States Government ◽  
Phase 3 ◽  
Efficacy Trials ◽  
Combining Data ◽  
The World ◽  
States Government ◽  
Common Scale ◽  
Aid Decision

Vaccine-induced neutralizing antibodies (nAbs) are key biomarkers considered to be associated with vaccine efficacy. In United States Government-sponsored phase 3 efficacy trials of COVID-19 vaccines, nAbs are measured by two different validated pseudovirus-based SARS-CoV-2 neutralization assays, with each trial using one of the two assays. Here we describe and compare the nAb titers obtained in the two assays. We observe that one assay consistently yielded higher nAb titers than the other when both assays were performed on the World Health Organization's anti-SARS-CoV-2 immunoglobulin International Standard, COVID-19 convalescent sera, and mRNA-1273 vaccinee sera. To overcome the challenge this difference in readout poses in comparing/combining data from the two assays, we evaluate three calibration approaches and show that readouts from the two assays can be calibrated to a common scale. These results may aid decision-making based on data from these assays for the evaluation and licensure of new or adapted COVID-19 vaccines.

scholarly journals SARS-CoV-2 vaccines strategies: a comprehensive review of phase 3 candidates

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Nikolaos C. Kyriakidis ◽  
Andrés López-Cortés ◽  
Eduardo Vásconez González ◽  
Alejandra Barreto Grimaldos ◽  
Esteban Ortiz Prado
Keyword(s):  
Neutralizing Antibodies ◽  
Large Scale ◽  
Vaccine Development ◽  
Rna Virus ◽  
Protein S ◽  
Effective Vaccine ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Advantages And Disadvantages ◽  
The World

AbstractThe new SARS-CoV-2 virus is an RNA virus that belongs to the Coronaviridae family and causes COVID-19 disease. The newly sequenced virus appears to originate in China and rapidly spread throughout the world, becoming a pandemic that, until January 5th, 2021, has caused more than 1,866,000 deaths. Hence, laboratories worldwide are developing an effective vaccine against this disease, which will be essential to reduce morbidity and mortality. Currently, there more than 64 vaccine candidates, most of them aiming to induce neutralizing antibodies against the spike protein (S). These antibodies will prevent uptake through the human ACE-2 receptor, thereby limiting viral entrance. Different vaccine platforms are being used for vaccine development, each one presenting several advantages and disadvantages. Thus far, thirteen vaccine candidates are being tested in Phase 3 clinical trials; therefore, it is closer to receiving approval or authorization for large-scale immunizations.

Security Council

1963 ◽  
Vol 17 (1) ◽  
pp. 226-230
Keyword(s):  
United States ◽  
Soviet Union ◽  
International Law ◽  
Security Council ◽  
The United States ◽  
United States Government ◽  
The Soviet Union ◽  
The World ◽  
Peace And Security ◽  
States Government

The Security Council discussed this question at its 1022nd–1025th meetings, on October 23–25, 1962. It had before it a letter dated October 22, 1962, from the permanent representative of the United States, in which it was stated that the establishment of missile bases in Cuba constituted a grave threat to the peace and security of the world; a letter of the same date from the permanent representative of Cuba, claiming that the United States naval blockade of Cuba constituted an act of war; and a letter also dated October 22 from the deputy permanent representative of the Soviet Union, emphasizing that Soviet assistance to Cuba was exclusively designed to improve Cuba's defensive capacity and that the United States government had committed a provocative act and an unprecedented violation of international law in its blockade.

A Phase 3, Randomized, Open-label, Noninferiority Trial Evaluating Anti-Rabies Monoclonal Antibody Cocktail (TwinrabTM) Against Human Rabies Immunoglobulin (HRIG)

2020 ◽  
Author(s):  
Kevinkumar Kansagra ◽  
Deven Parmar ◽  
Sanjeev Kumar Mendiratta ◽  
Jatin Patel ◽  
Shuchi Joshi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
World Health ◽  
Human Rabies ◽  
Open Label ◽  
Phase 3 ◽  
Noninferiority Trial ◽  
Rabid Animal ◽  
Antibody Cocktail

Abstract Background Limited supply, cost and potential for severe adverse effects observed with the blood derived rabies immunoglobulin products has led to search for alternative therapies. This issue has been addressed by developing an anti-rabies monoclonal antibody cocktail. Methods This is a phase 3, randomized, open-label, noninferiority trial conducted in patients with World Health Organization (WHO) category III exposure with suspected rabid animal. Eligible patients were assigned to either the test arm, TwinrabTM (docaravimab and miromavimab) or the reference arm, human rabies immunoglobulin (HRIG; Imogam® Rabies-HT), in a ratio of 1:1. The primary endpoint was the comparison of responder rates between the 2 arms assessed as percentage of those with rabies virus neutralizing antibodies titers ≥0.5 IU/mL on day 14. Results A total of 308 patients were equally randomized into the 2 arms. In the per-protocol (PP) population, there were 90.21% responders in the TwinrabTM arm and 94.37% in the HRIG arm. The geometric mean of rapid fluorescent foci inhibition test titers in the PP on day 14 were 4.38 and 4.85 IU/mL, for the TwinrabTM and HRIG arms, respectively. There were no deaths or serious adverse events reported. Conclusions This study confirmed that TwinrabTM is noninferior to HRIG in terms of providing an unbroken window of protection up to day 84. This trial in healthy adults with WHO category III exposure from suspected rabid animal also establishes the safety of TwinrabTM in patients with 1 WHO approved vaccine regimen (Essen). Clinical Trials Registration CTRI/2017/07/009038.

scholarly journals A mixed-method exploration into the experience of members of the FAO/WHO International Food Safety Authorities Network (INFOSAN): study protocol

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e027091 ◽  
Author(s):  
Carmen Joseph Savelli ◽  
Céu Mateus
Keyword(s):  
Food Safety ◽  
Online Survey ◽  
Phase 1 ◽  
Deep Understanding ◽  
Global Network ◽  
World Health ◽  
Ethical Review ◽  
Phase 3 ◽  
Medicine Research ◽  
The World

IntroductionThe International Food Safety Authorities Network (INFOSAN) is a global network of national food safety authorities from 188 countries, managed jointly by the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO), which facilitates the rapid exchange of information during food safety related events. The proposed research will interrogate INFOSAN in order to describe and explore the experiences of members and better understand the role of the network in mitigating the burden of foodborne illness around the world.MethodsExamined through a community of practice lens, a three-phase research design will combine quantitative and qualitative methods (including website analytics in phase 1, online survey administration in phase 2 and semistructured interviews in phase 3) to elicit a broad and deep understanding of the network operation and member experiences.AnalysisIn phases 1 and 2, quantitative data collected from the INFOSAN Community website and the online questionnaires will be analysed using descriptive summary statistics. In phase 3, interpretative phenomenological analysis will be used to engage in a dialogue with study participants to explore and describe their lived experiences regarding participation in activities related to INFOSAN. An important aspect of the overall analysis will be triangulation of the information collected from each phase, including quantitative indicators and qualitative value stories, in order to provide a robust understanding of member experience.Ethics and disseminationThis study has undergone ethical review and has received approval from Lancaster University’s Faculty of Health and Medicine Research Ethics Committee, as well as the ethics review committee of the WHO. Findings from the study will be disseminated as a PhD thesis submitted to Lancaster University. In addition, results of the research shall be submitted for publication to relevant academic or professional conferences and journals or other media, including books or websites.

The Limits of Self-Determination: The Case of the Katanga Secession

1962 ◽  
Vol 56 (2) ◽  
pp. 404-416 ◽  
Author(s):  
René Lemarchand
Keyword(s):  
The United States ◽  
Self Determination ◽  
United States Government ◽  
Small States ◽  
The World ◽  
States Government ◽  
Republic Of The Congo ◽  
The Republic ◽  
The Government ◽  
The Right

Not the least paradoxical aspect of the United Nations mandate in the Congo, as described in the three-power resolution adopted by the Security Council on November 24, 1961, is that it was designed to prevent the exercise of a right which is explicitly recognized by the Charter. In effect, by “completely rejecting the claim of the Katanga as a sovereign independent Nation” and “recognizing the government of the Republic of the Congo as exclusively responsible for the conduct of the external affairs of the Congo,” the authors of the resolution clearly denied the provincial authorities of the Katanga the right to self-determination. Similarly, the support given by the United States government to the resolution, reaffirmed in several official statements, seems hardly compatible with our long-standing moral commitment to the Wilsonian principle that “the small states of the world have a right to enjoy the same respect for their sovereignty and territorial integrity that the great and powerful states expect and insist upon.” Actually, what may at first sight appear to be a sign of inconsistency is rather a reflection of the fundamental ambiguity in the concept of self-determination.

Hitting the Brakes: Toyota in Crisis

2011 ◽  
Vol 7 (2) ◽  
pp. 114-136
Author(s):  
John A. Parnell ◽  
John E. Spillan ◽  
Marlon R. McPhattar ◽  
Donald L. Lester
Keyword(s):  
Quality Control ◽  
The United States ◽  
Poor Quality ◽  
Warning Signs ◽  
United States Government ◽  
Vehicle Safety ◽  
Early Warning Signs ◽  
The World ◽  
States Government ◽  
Negative Publicity

The decade from 2000 until 2010 was a turbulent time for Toyota Motor Company. The carmaker came under significant criticism from the United States government, consumers throughout the world, and media critics amid allegations of poor quality control and vehicle safety concerns. Problems with accelerators and brake systems were found on several of its most popular models, a situation initially exacerbated by the slow and somewhat tentative response from top management. Toyota was accused of not addressing early warning signs that appeared several years before the crisis received intense negative publicity. Toyota struggled to retain the confidence of consumers and governmental regulators, eventually recalling approximately eight million automobiles.

scholarly journals Vaccines against COVID-19 – Catching the Rays of Hope

2021 ◽  
pp. 469-488
Author(s):  
Suresh Kumar Srinivasamurthy ◽  
Laxminarayana Kurady Bairy
Keyword(s):  
Herd Immunity ◽  
Clinical Impact ◽  
Morbidity And Mortality ◽  
Phase 3 ◽  
Vaccine Candidates ◽  
Practical Possibility ◽  
Efficacy Trials ◽  
The World ◽  
The Status ◽  
Early Phase Clinical Trials

COVID-19 pandemic has affected the world in all its dimensions. With herd immunity being a distant and non-practical possibility, vaccination remains most tractable approach to reduce morbidity and mortality. Several early phase clinical trials have proved the immunogenicity of vaccines. The efficacy trials have shown reduction in chance of acquiring COVID-19 disease after vaccination. The vaccines approved for emergency use have reported efficacy above 50% thus making them important public health tool in controlling the pandemic. Nevertheless, several questions remain elusive such as whether these approved vaccines are effective against newer variants of the virus; whether vaccination prevents transmission of the virus in the community; clinical impact of vaccination on morbidity and mortality. This review aims to elucidate the status of vaccine candidates in advanced trials along with the vaccines, which have been granted emergency approvals. Further, we collate the data on vaccines efficacy phase 3 trials and their probability of efficacy against newer variants.

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