scholarly journals Correlates of Vaccine-Induced Protection against SARS-CoV-2

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 238
Author(s):  
Till Koch ◽  
Sibylle C. Mellinghoff ◽  
Parichehr Shamsrizi ◽  
Marylyn M. Addo ◽  
Christine Dahlke
Keyword(s):  
Economic Recession ◽  
European Medicines Agency ◽  
Comprehensive Overview ◽  
Vaccine Candidates ◽  
Clinical Phase ◽  
Efficacy Trials ◽  
Generation Vaccine ◽  
Efficacy Measures ◽  
Infection Disease ◽  
One Year

We are in the midst of a pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). SARS-CoV-2 has caused more than two million deaths after one year of the pandemic. The world is experiencing a deep economic recession. Safe and effective vaccines are needed to prevent further morbidity and mortality. Vaccine candidates against COVID-19 have been developed at an unprecedented speed, with more than 200 vaccine candidates currently under investigation. Among those, 20 candidates have entered the clinical Phase 3 to evaluate efficacy, and three have been approved by the European Medicines Agency. The aim of immunization is to act against infection, disease and/or transmission. However, the measurement of vaccine efficacy is challenging, as efficacy trials need to include large cohorts with verum and placebo cohorts. In the future, this will be even more challenging as further vaccine candidates will receive approval, an increasing number of humans will receive vaccinations and incidence might decrease. To evaluate novel and second-generation vaccine candidates, randomized placebo-controlled trials might not be appropriate anymore. Correlates of protection (CoP) could be an important tool to evaluate novel vaccine candidates, but vaccine-induced CoP have not been clearly defined for SARS-CoV-2 vaccines. In this review, we report on immunogenicity against natural SARS-CoV-2 infection, vaccine-induced immune responses and discuss immunological markers that can be linked to protection. By discussing the immunogenicity and efficacy of forerunner vaccines, we aim to give a comprehensive overview of possible efficacy measures and CoP.

scholarly journals Current Status of Zika Virus Vaccines: Successes and Challenges

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 266 ◽  
Author(s):  
Aryamav Pattnaik ◽  
Bikash R. Sahoo ◽  
Asit K. Pattnaik
Keyword(s):  
Zika Virus ◽  
Viral Infections ◽  
Current Status ◽  
Effective Vaccine ◽  
Congenital Diseases ◽  
Vaccine Candidates ◽  
Efficacy Trials ◽  
Nucleic Acid Vaccines ◽  
Funding Agencies ◽  
Inactivated Vaccines

The recently emerged Zika virus (ZIKV) spread to the Americas, causing a spectrum of congenital diseases including microcephaly in newborn and Guillain-Barré syndrome (GBS) in adults. The unprecedented nature of the epidemic and serious diseases associated with the viral infections prompted the global research community to understand the immunopathogenic mechanisms of the virus and rapidly develop safe and efficacious vaccines. This has led to a number of ZIKV vaccine candidates that have shown significant promise in human clinical trials. These candidates include nucleic acid vaccines, inactivated vaccines, viral-vectored vaccines, and attenuated vaccines. Additionally, a number of vaccine candidates have been shown to protect animals in preclinical studies. However, as the epidemic has waned in the last three years, further development of the most promising vaccine candidates faces challenges in clinical efficacy trials, which is needed before a vaccine is brought to licensure. It is important that a coalition of government funding agencies and private sector companies is established to move forward with a safe and effective vaccine ready for deployment when the next ZIKV epidemic occurs.

scholarly journals Progress and challenges in TB vaccine development

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 199 ◽  
Author(s):  
Gerald Voss ◽  
Danilo Casimiro ◽  
Olivier Neyrolles ◽  
Ann Williams ◽  
Stefan H.E. Kaufmann ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Vaccine Development ◽  
Scientific Progress ◽  
Human Infection ◽  
Experimental Medicine ◽  
Vaccine Platform ◽  
Vaccine Candidates ◽  
Clinical Endpoints ◽  
Immune Correlates ◽  
Efficacy Trials

The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our “failed” trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development.

Short- and long-term immunogenicity and protection induced by non-replicating smallpox vaccine candidates in mice and comparison with the traditional 1st generation vaccine

Vaccine ◽  
2008 ◽  
Vol 26 (14) ◽  
pp. 1794-1804 ◽  
Author(s):  
Audrey Ferrier-Rembert ◽  
Robert Drillien ◽  
Jean-Nicolas Tournier ◽  
Daniel Garin ◽  
Jean-Marc Crance
Keyword(s):  
Smallpox Vaccine ◽  
Vaccine Candidates ◽  
Generation Vaccine ◽  
Short And Long Term

Interferon beta failure predicted by EMA criteria or isolated MRI activity in multiple sclerosis

2013 ◽  
Vol 20 (5) ◽  
pp. 566-576 ◽  
Author(s):  
Luca Prosperini ◽  
Chiara Rosa Mancinelli ◽  
Laura De Giglio ◽  
Floriana De Angelis ◽  
Valeria Barletta ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Interferon Beta ◽  
European Medicines Agency ◽  
First Year ◽  
Resonance Imaging ◽  
T2 Lesions ◽  
Increased Risk ◽  
Magnetic Resonance Imaging Mri ◽  
One Year

Objective: The objective of this paper is to investigate four-year outcomes of interferon beta (IFNB)-treated patients with multiple sclerosis (MS) according to their clinical or magnetic resonance imaging (MRI) activity status at first year of treatment. Methods: A total of 370 patients with MS duration ≤5 years before IFNB start were followed-up for four years. The optimal threshold for one-year MRI activity that more accurately predicted subsequent relapses or disability worsening was identified. The risk of relapses and disability worsening after the first year was then estimated by propensity score (PS)-adjusted analyses in patients fulfilling European Medicines Agency (EMA) criteria for second-line escalation and in those with isolated MRI activity. Results: A total of 192 (51.9%) patients relapsed, and 66 (17.8%) worsened in disability from year 1 to 4 of follow-up. The more accurate threshold for one-year MRI activity was the occurrence of ≥1 enhancing or ≥2 new T2-lesions. An increased risk of relapses and disability worsening was found in either patients fulfilling EMA criteria (hazard ratio (HR) = 3.69, and HR = 6.02) and in those experiencing isolated MRI activity (HR = 3.15, and HR = 5.31) at first year of treatment, when compared with stable patients (all p values <0.001). Conclusion: The four-year outcomes of patients with isolated MRI activity did not differ from those fulfilling EMA criteria at first year of IFNB treatment.

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.

scholarly journals Validation and automation of a high-throughput multi-targeted method for semi-quantification of endogenous metabolites from different biological matrices using tandem mass spectrometry

2018 ◽  
Author(s):  
Jatin Nandania ◽  
Gopal Peddinti ◽  
Alberto Pessia ◽  
Meri Kokkonen ◽  
Vidya Velagapudi
Keyword(s):  
Biomarker Discovery ◽  
R Package ◽  
Epidemiological Studies ◽  
European Medicines Agency ◽  
Biological Matrices ◽  
Research Fields ◽  
Wide Range ◽  
Cross Platform ◽  
One Year ◽  
Endogenous Metabolites

AbstractThe use of metabolomics profiling to understand metabolism under different physiological states has increased in recent years, which created the need for robust analytical platforms. Here, we present a validated method for targeted and semi-quantitative analysis of 102 polar metabolites that covers major metabolic pathways from 24 classes in a single 17.5-min assay. The method has been optimized for a wide range of biological matrices from various organisms, and involves automated sample preparation, and data processing using in-house developed R package. To ensure reliability, the method was validated for accuracy, precision, selectivity, specificity, linearity, recovery, and stability according to European Medicines Agency guidelines. We demonstrated excellent repeatability of the retention times (CV<4%), calibration curves (R2≥0.980) in their respective wide dynamic concentration ranges (CV<3%), and concentrations (CV<25%) of quality control samples interspersed within 25 batches analyzed over a period of one-year. The robustness was demonstrated through high correlation between metabolite concentrations measured using our method and NIST reference values (R2=0.967), including cross-platform comparability against the BIOCRATES AbsoluteIDQp180 kit (R2=0.975) and NMR analyses (R2=0.884). We have shown that our method can be successfully applied in many biomedical research fields and clinical trials, including epidemiological studies for biomarker discovery. In summary, a thorough validation demonstrated that our method is reproducible, robust, reliable, and suitable for metabolomics studies.

scholarly journals Development of a TB vaccine trial site in Africa and lessons from the Ebola experience.

2020 ◽  
Author(s):  
Grace Kaguthi ◽  
Videlis Nduba ◽  
Prisca Rabuogi ◽  
Douglas Okelloh ◽  
Samuel G. Ouma ◽  
...  
Keyword(s):  
United States ◽  
Disease Incidence ◽  
Vaccine Trial ◽  
The United States ◽  
European Medicines Agency ◽  
Concerted Effort ◽  
Trial Site ◽  
Vaccine Candidates ◽  
Limited Efficacy ◽  
Global Threat

Abstract Tuberculosis is the deadliest infection of our time. In contrast, about 11,000 people died of Ebola between 2014 and 2016. Despite this manifest difference in mortality, there is now a vaccine licensed in the United States and by the European Medicines Agency, with up to 100% efficacy against Ebola. The developments that led to the trialing of the Ebola vaccine were historic and unprecedented. The single licensed TB vaccine (BCG) has limited efficacy. There is a dire need for a more efficacious TB vaccine. To deploy such vaccines, trials are needed in sites that combine high disease incidence and research infrastructure. We describe our twelve-year experience building a TB vaccine trial site in contrast to the process in the recent Ebola outbreak. There are additional differences. Relative to the Ebola pipeline, TB vaccines have fewer trials and a paucity of government and industry led trials. While pathogens have varying levels of difficulty in the development of new vaccine candidates, there yet appears to be greater interest in funding and coordinating Ebola interventions. TB is a global threat that requires similar concerted effort for elimination.

scholarly journals Robust immune responses after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2 experienced individuals

2021 ◽  
Author(s):  
Marie I. Samanovic ◽  
Amber R. Cornelius ◽  
Sophie L. Gray-Gaillard ◽  
Joseph Richard Allen ◽  
Trishala Karmacharya ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Efficacy ◽  
Vaccine Dose ◽  
Prior History ◽  
Vaccine Candidates ◽  
Antibody Secreting Cell ◽  
Cell Responses ◽  
Efficacy Trials ◽  
History Of ◽  
Humoral Responses

ABSTRACTThe use of COVID-19 vaccines will play a major role in helping to end the pandemic that has killed millions worldwide. COVID-19 vaccine candidates have resulted in robust humoral responses and protective efficacy in human trials, but efficacy trials excluded individuals with prior diagnosis of COVID-19. As a result, little is known about how immune responses induced by mRNA vaccine candidates differ in individuals who recovered from COVID-19. Here, we evaluated longitudinal immune responses to two-dose BNT162b2 mRNA vaccination in 13 adults who recovered from COVID-19, compared to 19 adults who did not have prior COVID-19 diagnosis. Consistent with prior studies of mRNA vaccines, we observed robust cytotoxic CD8 T cell responses in both cohorts. Furthermore, SARS-CoV-2-naive individuals had progressive increases in humoral and antigen-specific antibody-secreting cell (ASC) responses following each dose of vaccine, whereas SARS-CoV-2-experienced individuals demonstrated strong humoral and antigen-specific ASC responses to the first dose but muted responses to the second dose of the vaccine for the time points studied. Together, these data highlight the relevance of immunological history for understanding vaccine immune responses and may have significant implications for personalizing mRNA vaccination regimens used to prevent COVID-19.One Sentence SummaryPrior history of COVID-19 affects adaptive immune responses to mRNA vaccination.

scholarly journals COVID-19 vaccines that reduce symptoms but do not block infection need higher coverage and faster rollout to achieve population impact

2020 ◽  
Author(s):  
David A. Swan ◽  
Chloe Bracis ◽  
Holly Janes ◽  
Mia Moore ◽  
Laura Matrajt ◽  
...  
Keyword(s):  
No Reduction ◽  
King County ◽  
Vaccine Candidates ◽  
Symptomatic Disease ◽  
Population Impact ◽  
Susceptibility To Infection ◽  
Infection Susceptibility ◽  
Asymptomatic Infections ◽  
One Year ◽  
The U.S

AbstractBackgroundSeveral COVID-19 vaccine candidates are in the final stage of testing. Interim trial results for two vaccines suggest at least 90% efficacy against symptomatic disease (VEDIS). It remains unknown whether this efficacy is mediated predominately by lowering SARS-CoV-2 infection susceptibility (VESUSC) or development of symptoms after infection (VESYMP). A vaccine with high VESYMP but low VESUSC has uncertain population impact.MethodsWe developed a mathematical model of SARS-CoV-2 transmission, calibrated to demographic, physical distancing and epidemic data from King County, Washington. Different rollout scenarios starting December 2020 were simulated assuming different combinations of VESUSC and VESYMP resulting in up to 100% VEDIS with constant vaccine effects over 1 year. We assumed no further increase in physical distancing despite expanding case numbers and no reduction of infectivity upon infection conditional on presence of symptoms. Proportions of cumulative infections, hospitalizations and deaths prevented over 1 year from vaccination start are reported.ResultsRollouts of 1M vaccinations (5,000 daily) using vaccines with 50% VEDIS are projected to prevent 30%-58% of infections and 38%-58% of deaths over one year. In comparison, vaccines with 90% VEDIS are projected to prevent 47%-78% of the infections and 58%-77% of deaths over one year. In both cases, there is a greater reduction if VEDIS is mediated mostly by VESUSC. The use of a “symptom reducing” vaccine will require twice as many people vaccinated than a “susceptibility reducing” vaccine with the same 90% VEDIS to prevent 50% of the infections and death over one year. Delaying the start of the vaccination by 3 months decreases the expected population impact by approximately 40%.ConclusionsVaccines which prevent COVID-19 disease but not SARS-CoV-2 infection, and thereby shift symptomatic infections to asymptomatic infections, will prevent fewer infections and require larger and faster vaccination rollouts to have population impact, compared to vaccines that reduce susceptibility to infection. If uncontrolled transmission across the U.S. continues, then expected vaccination in Spring 2021 will provide only limited benefit.

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