scholarly journals A method to estimate probability of disease and vaccine efficacy from clinical trial immunogenicity data

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Julie Dudášová ◽  
Regina Laube ◽  
Chandni Valiathan ◽  
Matthew C. Wiener ◽  
Ferdous Gheyas ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Vaccine Efficacy ◽  
Vaccine Development ◽  
Current Effort ◽  
Standard Case ◽  
Clinical Trial Simulations ◽  
Case Count ◽  
Standard Estimate ◽  
Response Biomarker ◽  
Biomarker Data

AbstractVaccine efficacy is often assessed by counting disease cases in a clinical trial. A new quantitative framework proposed here (“PoDBAY,” Probability of Disease Bayesian Analysis), estimates vaccine efficacy (and confidence interval) using immune response biomarker data collected shortly after vaccination. Given a biomarker associated with protection, PoDBAY describes the relationship between biomarker and probability of disease as a sigmoid probability of disease (“PoD”) curve. The PoDBAY framework is illustrated using clinical trial simulations and with data for influenza, zoster, and dengue virus vaccines. The simulations demonstrate that PoDBAY efficacy estimation (which integrates the PoD and biomarker data), can be accurate and more precise than the standard (case-count) estimation, contributing to more sensitive and specific decisions than threshold-based correlate of protection or case-count-based methods. For all three vaccine examples, the PoD fit indicates a substantial association between the biomarkers and protection, and efficacy estimated by PoDBAY from relatively little immunogenicity data is predictive of the standard estimate of efficacy, demonstrating how PoDBAY can provide early assessments of vaccine efficacy. Methods like PoDBAY can help accelerate and economize vaccine development using an immunological predictor of protection. For example, in the current effort against the COVID-19 pandemic it might provide information to help prioritize (rank) candidates both earlier in a trial and earlier in development.

scholarly journals Additional evidence on the efficacy of different Akirin vaccines assessed on Anopheles arabiensis (Diptera: Culicidae)

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Blaženka D. Letinić ◽  
Marinela Contreras ◽  
Yael Dahan-Moss ◽  
Ingrid Linnekugel ◽  
José de la Fuente ◽  
...  
Keyword(s):  
Vector Control ◽  
Aedes Albopictus ◽  
Malaria Vector ◽  
Vaccine Efficacy ◽  
Anopheles Arabiensis ◽  
Vaccine Development ◽  
Target Antigen ◽  
Control Methods ◽  
Protective Response ◽  
Current Vector

Abstract Background Anopheles arabiensis is an opportunistic malaria vector that rests and feeds outdoors, circumventing current indoor vector control methods. Furthermore, this vector will readily feed on both animals and humans. Targeting this vector while feeding on animals can provide an additional intervention for the current vector control activities. Previous results have displayed the efficacy of using Subolesin/Akirin ortholog vaccines for the control of multiple ectoparasite infestations. This made Akirin a potential antigen for vaccine development against An. arabiensis. Methods The efficacy of three antigens, namely recombinant Akirin from An. arabiensis, recombinant Akirin from Aedes albopictus, and recombinant Q38 (Akirin/Subolesin chimera) were evaluated as novel interventions for An. arabiensis vector control. Immunisation trials were conducted based on the concept that mosquitoes feeding on vaccinated balb/c mice would ingest antibodies specific to the target antigen. The antibodies would interact with the target antigen in the arthropod vector, subsequently disrupting its function. Results All three antigens successfully reduced An. arabiensis survival and reproductive capacities, with a vaccine efficacy of 68–73%. Conclusions These results were the first to show that hosts vaccinated with recombinant Akirin vaccines could develop a protective response against this outdoor malaria transmission vector, thus providing a step towards the development of a novel intervention for An. arabiensis vector control. Graphic Abstract

Equitable Access to Research Benefits: Considerations for COVID-19 Vaccine Development and Clinical Trial Crossover

2021 ◽  
Vol 21 (3) ◽  
pp. 86-88
Author(s):  
Danish Zaidi ◽  
Jennifer Miller ◽  
Tanvee Varma ◽  
Dowin Boatright ◽  
Phoebe Friesen
Keyword(s):  
Clinical Trial ◽  
Vaccine Development ◽  
Equitable Access

scholarly journals Intention to Be Vaccinated for COVID-19 among Italian Nurses during the Pandemic

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 500
Author(s):  
Marco Trabucco Aurilio ◽  
Francesco Saverio Mennini ◽  
Simone Gazzillo ◽  
Laura Massini ◽  
Matteo Bolcato ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Online Survey ◽  
Vaccine Development ◽  
Vaccine Coverage ◽  
World Health ◽  
Vaccine Hesitancy ◽  
Effective Vaccine ◽  
Online Questionnaire ◽  
Cross Sectional ◽  
Female Sex

Background: While the COVID-19 pandemic has spread globally, health systems are overwhelmed by both direct and indirect mortality from other treatable conditions. COVID-19 vaccination was crucial to preventing and eliminating the disease, so vaccine development for COVID-19 was fast-tracked worldwide. Despite the fact that vaccination is commonly recognized as the most effective approach, according to the World Health Organization (WHO), vaccine hesitancy is a global health issue. Methods: We conducted a cross-sectional online survey of nurses in four different regions in Italy between 20 and 28 December 2020 to obtain data on the acceptance of the upcoming COVID-19 vaccination in order to plan specific interventions to increase the rate of vaccine coverage. Results: A total of 531 out of the 5000 nurses invited completed the online questionnaire. Most of the nurses enrolled in the study (73.4%) were female. Among the nurses, 91.5% intended to accept vaccination, whereas 2.3% were opposed and 6.2% were undecided. Female sex and confidence in vaccine efficacy represent the main predictors of vaccine intention among the study population using a logistic regression model, while other factors including vaccine safety concerns (side effects) were non-significant. Conclusions: Despite the availability of a safe and effective vaccine, intention to be vaccinated was suboptimal among nurses in our sample. We also found a significant number of people undecided as to whether to accept the vaccine. Contrary to expectations, concerns about the safety of the vaccine were not found to affect the acceptance rate; nurses’ perception of vaccine efficacy and female sex were the main influencing factors on attitudes toward vaccination in our sample. Since the success of the COVID-19 immunization plan depends on the uptake rate, these findings are of great interest for public health policies. Interventions aimed at increasing employee awareness of vaccination efficacy should be promoted among nurses in order to increase the number of vaccinated people.

scholarly journals Quantifying the Impact of Natural Immunity on Rotavirus Vaccine Efficacy Estimates: A Clinical Trial in Dhaka, Bangladesh (PROVIDE) and a Simulation Study

2018 ◽  
Vol 217 (6) ◽  
pp. 861-868 ◽  
Author(s):  
Elizabeth T Rogawski ◽  
James A Platts-Mills ◽  
E Ross Colgate ◽  
Rashidul Haque ◽  
K Zaman ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Simulation Study ◽  
Vaccine Efficacy ◽  
Natural Immunity ◽  
Rotavirus Vaccine ◽  
The Impact

scholarly journals Application of the matched nested case-control design to the secondary analysis of trial data

2020 ◽  
Author(s):  
Christopher Partlett ◽  
Nigel J Hall ◽  
Alison Leaf ◽  
Edmund Juszczak ◽  
Louise Linsell
Keyword(s):  
Clinical Trial ◽  
Case Control Study ◽  
Secondary Analysis ◽  
Control Design ◽  
Case Control ◽  
Necrotising Enterocolitis ◽  
Trial Data ◽  
Standard Case ◽  
Nested Case Control ◽  
Control Study

Abstract Background A nested case-control study is an efficient design that can be embedded within an existing cohort study or randomised trial. It has a number of advantages compared to the conventional case-control design, and has the potential to answer important research questions using untapped prospectively collected data. Methods We demonstrate the utility of the matched nested case-control design by applying it to a secondary analysis of the Abnormal Doppler Enteral Prescription Trial. We investigated the role of milk feed type and changes in milk feed type in the development of necrotising enterocolitis in a group of 398 high risk growth-restricted preterm infants. Results Using matching, we were able to generate a comparable sample of controls selected from the same population as the cases. In contrast to the standard case-control design, exposure status was ascertained prior to the outcome event occurring and the comparison between the cases and matched controls could be made at the point at which the event occurred. This enabled us to reliably investigate the temporal relationship between feed type and necrotising enterocolitis. Conclusions A matched nested case-control study can be used to identify credible associations in a secondary analysis of clinical trial data where the exposure of interest was not randomised, and has several advantages over a standard case-control design. This method offers the potential to make reliable inferences in scenarios where it would be unethical or impractical to perform a randomised clinical trial.

scholarly journals Recognition of conserved antigens by Th17 cells provides broad protection against pulmonaryHaemophilus influenzaeinfection

2018 ◽  
Vol 115 (30) ◽  
pp. E7149-E7157 ◽  
Author(s):  
Wenchao Li ◽  
Xinyun Zhang ◽  
Ying Yang ◽  
Qingqin Yin ◽  
Yan Wang ◽  
...  
Keyword(s):  
Th17 Cells ◽  
Antigenic Variation ◽  
Vaccine Development ◽  
Community Acquired Pneumonia ◽  
Chronic Obstructive ◽  
Current Effort ◽  
Obstructive Pulmonary Disease ◽  
Th17 Response ◽  
Homologous Strain ◽  
Different Strains

NontypeableHaemophilus influenzae(NTHi) is a major cause of community acquired pneumonia and exacerbation of chronic obstructive pulmonary disease. A current effort in NTHi vaccine development has focused on generating humoral responses and has been greatly impeded by antigenic variation among the numerous circulating NTHi strains. In this study, we showed that pulmonary immunization of mice with killed NTHi generated broad protection against lung infection by different strains. While passive transfer of immune antibodies protected only against the homologous strain, transfer of immune T cells conferred protection against both homologous and heterologous strains. Further characterization revealed a strong Th17 response that was cross-reactive with different NTHi strains. Responding Th17 cells recognized both cytosolic and membrane-associated antigens, while immune antibodies preferentially responded to surface antigens and were highly strain specific. We further identified several conserved proteins recognized by lung Th17 cells during NTHi infection. Two proteins yielding the strongest responses were tested as vaccine candidates by immunization of mice with purified proteins plus an adjuvant. Immunization induced antigen-specific Th17 cells that recognized different strains and, upon adoptive transfer, conferred protection. Furthermore, immunized mice were protected against challenge with not only NTHi strains but also a fully virulent, encapsulated strain. Together, these results show that the immune mechanism of cross-protection against pneumonia involves Th17 cells, which respond to a broad spectrum of antigens, including those that are highly conserved among NTHi strains. These mechanistic insights suggest that inclusion of Th17 antigens in subunit vaccines offers the advantage of inducing broad protection and complements the current antibody-based approaches.

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