scholarly journals The importance of time post-vaccination in determining the decrease in vaccine efficacy against SARS-CoV-2 variants of concern

2021 ◽  
Author(s):  
Yinon M. Bar-On ◽  
Elad Noor ◽  
Noam Gottlieb ◽  
Alex Sigal ◽  
Ron Milo
Keyword(s):  
Vaccine Efficacy ◽  
Strong Dependence ◽  
Similar Efficacy ◽  
Mitigation Strategies ◽  
High Efficacy ◽  
Breakthrough Infection ◽  
Post Vaccination ◽  
Open Question ◽  
The Impact ◽  
Efficacy Studies

With the development of high-efficacy vaccines against SARS-CoV-2, an urgent open question is whether currently available vaccines protect with similar efficacy against infection with SARS-CoV-2 variants of concern (VOC). Recent reports quantifying the extent by which VOC can evade vaccine immunity resulted in a range of estimates for the same VOC, which makes them difficult to interpret. One possible explanation for the discrepancies between different studies is an inconsistency in terms of the time post-vaccination of the sampled population. Here we present a model based on the observed correlation between antibody neutralization levels and vaccine efficacy, which demonstrates the impact of time post-vaccination on the comparison of the vaccine efficacy for VOC versus non-VOC infections. Our model predicts and exemplifies several possible consequences for vaccine efficacy in VOC infections: 1) a delay in the onset of vaccine efficacy against VOC; 2) a transient increase in susceptibility to breakthrough infection with VOC compared to non-VOC as a function of time after vaccination. We review preliminary data indicating that such phenomena are observed in studies of the B.1.1.7 and B.1.351 variants. We find that ignoring the strong dependence on the time post-vaccination can lead to contradictory reports of relative efficacy against VOC versus non-VOC, with implications on mitigation strategies against VOC and the design of vaccine efficacy studies.

scholarly journals The Impact of Serotype Cross-Protection on Vaccine Trials: DENVax as a Case Study

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 674
Author(s):  
Maíra Aguiar ◽  
Nico Stollenwerk
Keyword(s):  
Vaccine Efficacy ◽  
Careful Consideration ◽  
Dengue Vaccine ◽  
Serious Adverse Events ◽  
Post Vaccination ◽  
Vaccine Trials ◽  
Long Time ◽  
Health Need ◽  
The Impact ◽  
Over Time

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (CYD-TDV—Sanofi Pasteur) and DENVax (TAK 003—Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. Although Dengvaxia resulted in serious adverse events and had to be restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods of 12 and 18 months. Although better measurement over a long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, such as for Dengvaxia, we also noted, after comparing the VE estimations for 12- and 18-month periods, that vaccine efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, and brings up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.

scholarly journals SARS-CoV-2 vaccine antibody response and breakthrough infections in patients receiving dialysis

2021 ◽  
Author(s):  
Shuchi Anand ◽  
Maria E Montez-Rath ◽  
Jialin Han ◽  
Pablo Garcia ◽  
LinaCel Cadden ◽  
...  
Keyword(s):  
Antibody Response ◽  
Mitigation Strategies ◽  
Breakthrough Infection ◽  
Post Vaccination ◽  
Correlates Of Protection ◽  
Igg Index ◽  
Nested Case Control ◽  
High Throughput Assay ◽  
Prior Infection ◽  
Sentinel Population

Background: Patients receiving dialysis are a sentinel population for groups at high risk for death and disability from COVID-19. Understanding correlates of protection post-vaccination can inform immunization and mitigation strategies. Methods: Monthly since January 2021, we tested plasma from 4791 patients receiving dialysis for antibodies to the receptor-binding domain (RBD) of SARS-CoV-2 using a high-throughput assay. We qualitatively assessed the proportion without a detectable RBD response and among those with a response, semiquantitative median IgG index values. Using a nested case-control design, we matched each breakthrough case to five controls by age, sex, and vaccination-month to determine whether peak and pre-breakthrough RBD IgG index values were associated with risk for infection post-vaccination. Results: Among 2563 vaccinated patients, the proportion without a detectable RBD response increased from 6.6% [95% CI 5.5-8.1] in 14-30 days post-vaccination to 20.2% [95% CI 17.1-23.8], and median index values declined from 92.7 (95% CI 77.8-107.5) to 3.7 (95% CI 3.1-4.3) after 5 months. Persons with SARS-CoV-2 infection prior-to-vaccination had higher peak index values than persons without prior infection, but values equalized by 5 months (p=0.230). Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days pre-breakthrough. Peak and pre-breakthrough RBD values <23 (equivalent to <506 WHO BAU/mL) were associated with higher odds for breakthrough infection (OR: 3.7 [95% CI 2.0-6.8] and 9.8 [95% CI 2.9-32.8], respectively). Conclusions: The antibody response to SARS-CoV-2 vaccination wanes rapidly, and in persons receiving dialysis, the persisting antibody response is associated with risk for breakthrough infection.

scholarly journals The Impact of Serotype Cross-Protection on Vaccine Trials: DENVax as a Case Study

2020 ◽  
Author(s):  
Maíra Aguiar ◽  
Nico Stollenwerk
Keyword(s):  
Vaccine Efficacy ◽  
Careful Consideration ◽  
Dengue Vaccine ◽  
Serious Adverse Events ◽  
Post Vaccination ◽  
Vaccine Trials ◽  
Long Time ◽  
Health Need ◽  
The Impact ◽  
Over Time

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (Sanofi Pasteur) and DENVax (Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. While Dengvaxia resulted in serious adverse events and is restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods. Although better measurement over long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, we also compare the VE estimations for 12 and 18 months and we observe that the efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, bring up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.

scholarly journals The Balancing Role of Distribution Speed against Varying Efficacy Levels of COVID-19 Vaccines under Variants

2021 ◽  
Author(s):  
Daniel Kim ◽  
Pinar Keskinocak ◽  
Pelin Pekgun ◽  
Inci Yildirim
Keyword(s):  
Health Outcomes ◽  
Vaccine Efficacy ◽  
High Efficacy ◽  
Trade Offs ◽  
Before And After ◽  
Key Factor ◽  
Vaccine Distribution ◽  
The Impact ◽  
D Model

Objective: Recent mutations in SARS-CoV-2 raised concerns about diminishing vaccine effectiveness against COVID-19 caused by particular variants. Even with a high initial efficacy, if a vaccine efficacy drops significantly against variants, or if it cannot be distributed quickly, it is uncertain whether the vaccine can provide better health outcomes than other vaccines. Hence, we evaluated the trade-offs between speed of distribution vs. efficacy of multiple vaccines when variants emerge. Methods: We utilized a Susceptible-Infected-Recovered-Deceased (SIR-D) model to simulate the impact of immunization using different vaccines with varying efficacies and assessed the level of infection attack rate (IAR) under different speeds of vaccine distribution. Results: We found that a vaccine with low efficacy both before and after variants may outperform a vaccine with high efficacy if the former can be distributed more quickly. Particularly, a vaccine with 65% and 60% efficacy before and after the variants, respectively, can outperform a vaccine with 95% and 90% efficacy, if its distribution is 46% to 48% faster (with the selected study parameters). Conclusions: Our results show that speed is a key factor to a successful immunization strategy to control the COVID-19 pandemic even when the emerging variants may reduce the efficacy of a vaccine.

A MODELING SYSTEM FOR CLIMATE CHANGE RISK ASSESSMENT, MANAGEMENT AND HEDGING IN COASTAL AREAS

2017 ◽  
Author(s):  
Sergei Soldatenko ◽  
Sergei Soldatenko ◽  
Genrikh Alekseev ◽  
Genrikh Alekseev ◽  
Alexander Danilov ◽  
...  
Keyword(s):  
Climate Change ◽  
Risk Assessment ◽  
Coastal Areas ◽  
Mitigation Strategies ◽  
System Structure ◽  
The Arctic ◽  
Risk Modeling ◽  
Wide Range ◽  
Adverse Weather ◽  
The Impact

Every aspect of human operations faces a wide range of risks, some of which can cause serious consequences. By the start of 21st century, mankind has recognized a new class of risks posed by climate change. It is obvious, that the global climate is changing, and will continue to change, in ways that affect the planning and day to day operations of businesses, government agencies and other organizations and institutions. The manifestations of climate change include but not limited to rising sea levels, increasing temperature, flooding, melting polar sea ice, adverse weather events (e.g. heatwaves, drought, and storms) and a rise in related problems (e.g. health and environmental). Assessing and managing climate risks represent one of the most challenging issues of today and for the future. The purpose of the risk modeling system discussed in this paper is to provide a framework and methodology to quantify risks caused by climate change, to facilitate estimates of the impact of climate change on various spheres of human activities and to compare eventual adaptation and risk mitigation strategies. The system integrates both physical climate system and economic models together with knowledge-based subsystem, which can help support proactive risk management. System structure and its main components are considered. Special attention is paid to climate risk assessment, management and hedging in the Arctic coastal areas.

scholarly journals Psychological and Behavioral Predictors of Vaccine Efficacy: Considerations for COVID-19

2021 ◽  
pp. 174569162198924
Author(s):  
Annelise A. Madison ◽  
M. Rosie Shrout ◽  
Megan E. Renna ◽  
Janice K. Kiecolt-Glaser
Keyword(s):  
Risk Factors ◽  
Side Effects ◽  
Vaccine Efficacy ◽  
Psychological Factors ◽  
Behavioral Interventions ◽  
Vulnerable Groups ◽  
Behavioral Risk Factors ◽  
Behavioral Risk ◽  
Vaccine Response ◽  
The Impact

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidates are being evaluated, with the goal of conferring immunity on the highest percentage of people who receive the vaccine as possible. It is noteworthy that vaccine efficacy depends not only on the vaccine but also on characteristics of the vaccinated. Over the past 30 years, a series of studies has documented the impact of psychological factors on the immune system’s vaccine response. Robust evidence has demonstrated that stress, depression, loneliness, and poor health behaviors can impair the immune system’s response to vaccines, and this effect may be greatest in vulnerable groups such as the elderly. Psychological factors are also implicated in the prevalence and severity of vaccine-related side effects. These findings have generalized across many vaccine types and therefore may be relevant to the SARS-CoV-2 vaccine. In this review, we discuss these psychological and behavioral risk factors for poor vaccine responses, their relevance to the COVID-19 pandemic, as well as targeted psychological and behavioral interventions to boost vaccine efficacy and reduce side effects. Recent data suggest these psychological and behavioral risk factors are highly prevalent during the COVID-19 pandemic, but intervention research suggests that psychological and behavioral interventions can increase vaccine efficacy.

scholarly journals Improving Drought Tolerance in Mungbean (Vigna radiata L. Wilczek): Morpho-Physiological, Biochemical and Molecular Perspectives

Agronomy ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1534
Author(s):  
Chandra Mohan Singh ◽  
Poornima Singh ◽  
Chandrakant Tiwari ◽  
Shalini Purwar ◽  
Mukul Kumar ◽  
...  
Keyword(s):  
Drought Stress ◽  
Drought Tolerance ◽  
Crop Production ◽  
Mitigation Strategies ◽  
Theoretical Research ◽  
Whole Genome Sequence ◽  
Complex Nature ◽  
Drought Tolerant ◽  
Breeding Programmes ◽  
The Impact

Drought stress is considered a severe threat to crop production. It adversely affects the morpho-physiological, biochemical and molecular functions of the plants, especially in short duration crops like mungbean. In the past few decades, significant progress has been made towards enhancing climate resilience in legumes through classical and next-generation breeding coupled with omics approaches. Various defence mechanisms have been reported as key players in crop adaptation to drought stress. Many researchers have identified potential donors, QTLs/genes and candidate genes associated to drought tolerance-related traits. However, cloning and exploitation of these loci/gene(s) in breeding programmes are still limited. To bridge the gap between theoretical research and practical breeding, we need to reveal the omics-assisted genetic variations associated with drought tolerance in mungbean to tackle this stress. Furthermore, the use of wild relatives in breeding programmes for drought tolerance is also limited and needs to be focused. Even after six years of decoding the whole genome sequence of mungbean, the genome-wide characterization and expression of various gene families and transcriptional factors are still lacking. Due to the complex nature of drought tolerance, it also requires integrating high throughput multi-omics approaches to increase breeding efficiency and genomic selection for rapid genetic gains to develop drought-tolerant mungbean cultivars. This review highlights the impact of drought stress on mungbean and mitigation strategies for breeding high-yielding drought-tolerant mungbean varieties through classical and modern omics technologies.

scholarly journals Contributions of lipopolysaccharide and the type IVB secretion system to Coxiella burnetii vaccine efficacy and reactogenicity

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Carrie M. Long ◽  
Paul A. Beare ◽  
Diane C. Cockrell ◽  
Jonathan Fintzi ◽  
Mahelat Tesfamariam ◽  
...  
Keyword(s):  
Phase I ◽  
Coxiella Burnetii ◽  
Vaccine Efficacy ◽  
Q Fever ◽  
Secretion System ◽  
Cell Vaccine ◽  
Post Vaccination ◽  
Whole Cell Vaccine ◽  
Type Ivb Secretion ◽  
Type Ivb Secretion System

AbstractCoxiella burnetii is the bacterial causative agent of the zoonosis Q fever. The current human Q fever vaccine, Q-VAX®, is a fixed, whole cell vaccine (WCV) licensed solely for use in Australia. C. burnetii WCV administration is associated with a dermal hypersensitivity reaction in people with pre-existing immunity to C. burnetii, limiting wider use. Consequently, a less reactogenic vaccine is needed. Here, we investigated contributions of the C. burnetii Dot/Icm type IVB secretion system (T4BSS) and lipopolysaccharide (LPS) in protection and reactogenicity of fixed WCVs. A 32.5 kb region containing 23 dot/icm genes was deleted in the virulent Nine Mile phase I (NMI) strain and the resulting mutant was evaluated in guinea pig models of C. burnetii infection, vaccination-challenge, and post-vaccination hypersensitivity. The NMI ∆dot/icm strain was avirulent, protective as a WCV against a robust C. burnetii challenge, and displayed potentially altered reactogenicity compared to NMI. Nine Mile phase II (NMII) strains of C. burnetii that produce rough LPS, were similarly tested. NMI was significantly more protective than NMII as a WCV; however, both vaccines exhibited similar reactogenicity. Collectively, our results indicate that, like phase I LPS, the T4BSS is required for full virulence by C. burnetii. Conversely, unlike phase I LPS, the T4BSS is not required for vaccine-induced protection. LPS length does not appear to contribute to reactogenicity while the T4BSS may contribute to this response. NMI ∆dot/icm represents an avirulent phase I strain with full vaccine efficacy, illustrating the potential of genetically modified C. burnetii as improved WCVs.

scholarly journals Potential Impact of the Current and Future Climate on the Yield, Quality, and Climate Suitability for Tea [Camellia sinensis (L.) O. Kuntze]: A Systematic Review

Agronomy ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 619
Author(s):  
Sadeeka Layomi Jayasinghe ◽  
Lalit Kumar
Keyword(s):  
Climate Change ◽  
Future Climate ◽  
Mitigation Strategies ◽  
Extreme Weather Events ◽  
Impact Of Climate Change ◽  
Advantages And Disadvantages ◽  
Tea Quality ◽  
Climate Suitability ◽  
Yield Quality ◽  
The Impact

Even though climate change is having an increasing impact on tea plants, systematic reviews on the impact of climate change on the tea system are scarce. This review was undertaken to assess and synthesize the knowledge around the impacts of current and future climate on yield, quality, and climate suitability for tea; the historical roots and the most influential papers on the aforementioned topics; and the key adaptation and mitigation strategies that are practiced in tea fields. Our findings show that a large number of studies have focused on the impact of climate change on tea quality, followed by tea yield, while a smaller number of studies have concentrated on climate suitability. Three pronounced reference peaks found in Reference Publication Year Spectroscopy (RYPS) represent the most significant papers associated with the yield, quality, and climate suitability for tea. Tea yield increases with elevated CO2 levels, but this increment could be substantially affected by an increasing temperature. Other climatic factors are uneven rainfall, extreme weather events, and climate-driven abiotic stressors. An altered climate presents both advantages and disadvantages for tea quality due to the uncertainty of the concentrations of biochemicals in tea leaves. Climate change creates losses, gains, and shifts of climate suitability for tea habitats. Further studies are required in order to fill the knowledge gaps identified through the present review, such as an investigation of the interaction between the tea plant and multiple environmental factors that mimic real-world conditions and then studies on its impact on the tea system, as well as the design of ensemble modeling approaches to predict climate suitability for tea. Finally, we outline multifaceted and evidence-based adaptive and mitigation strategies that can be implemented in tea fields to alleviate the undesirable impacts of climate change.

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