Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
1,914
result(s) for
"Gilbert, Peter"
Sort by:
Evidence for antibody as a protective correlate for COVID-19 vaccines
A correlate of protection (CoP) is urgently needed to expedite development of additional COVID-19 vaccines to meet unprecedented global demand. To assess whether antibody titers may reasonably predict efficacy and serve as the basis of a CoP, we evaluated the relationship between efficacy and in vitro neutralizing and binding antibodies of 7 vaccines for which sufficient data have been generated. Once calibrated to titers of human convalescent sera reported in each study, a robust correlation was seen between neutralizing titer and efficacy (ρ = 0.79) and binding antibody titer and efficacy (ρ = 0.93), despite geographically diverse study populations subject to different forces of infection and circulating variants, and use of different endpoints, assays, convalescent sera panels and manufacturing platforms. Together with evidence from natural history studies and animal models, these results support the use of post-immunization antibody titers as the basis for establishing a correlate of protection for COVID-19 vaccines.
Journal Article
Sieve analysis to understand how SARS-CoV-2 diversity can impact vaccine protection
Beyond the primary endpoint of symptomatic COVID-19, sieve analyses that focus on SARS-CoV-2 infections will be particularly relevant to characterize the effect of viral variation on vaccine efficacy. Since many infections remain asymptomatic, the emphasis on symptomatic COVID-19 means that the vaccine could show excellent (trial defined) efficacy without blocking all SARS-CoV-2 infections. Current trials typically study vaccine efficacy against SARS-CoV-2 seroconversion at 3 to 6 monthly visits but can miss many infections because of waning nucleoprotein antibody detectability and limited RNA PCR nasal swab testing [6]. [...]it would be valuable for some vaccine efficacy trials to implement strategies to frequently test trial participants for SARS-CoV-2 infections and to sequence infections. [...]frequent screening for asymptomatic infections would allow to study how the protective efficacy of the vaccine against nasal carriage or asymptomatic infection depends on SARS-CoV-2 genetics. The distribution in gray represents the expected distribution in the placebo group, while the distribution in red represents the viruses infecting vaccine participants (after vaccine sieving). Since the vaccine presents the Spike to the immune system of vaccinated individuals, the distribution of hamming distances was restricted to Spike protein sequences to focus on sites relevant to the specificity of vaccine-induced immune responses.
Journal Article
chngpt: threshold regression model estimation and inference
Background
Threshold regression models are a diverse set of non-regular regression models that all depend on change points or thresholds. They provide a simple but elegant and interpretable way to model certain kinds of nonlinear relationships between the outcome and a predictor.
Results
The R package
chngpt
provides both estimation and hypothesis testing functionalities for four common variants of threshold regression models. All allow for adjustment of additional covariates not subjected to thresholding. We demonstrate the consistency of the estimating procedures and the type 1 error rates of the testing procedures by Monte Carlo studies, and illustrate their practical uses using an example from the study of immune response biomarkers in the context of Mother-To-Child-Transmission of HIV-1 viruses.
Conclusion
chngpt
makes several unique contributions to the software for threshold regression models and will make these models more accessible to practitioners interested in modeling threshold effects.
Journal Article
A Covid-19 Milestone Attained — A Correlate of Protection for Vaccines
The rapid identification of a correlate of protection for Covid-19 vaccines — on the basis of several harmonized randomized phase 3 trials using common validated assays — constitutes an important success in vaccinology.
Journal Article
Effect of Dengue Serostatus on Dengue Vaccine Safety and Efficacy
Concerns have been raised about the risk of severe dengue in children who were seronegative before receipt of a recently deployed dengue vaccine. In this study, data from field trials were analyzed to assess the effect of baseline serostatus on subsequent severe illness.
Journal Article
Correlates of Protection, Thresholds of Protection, and Immunobridging among Persons with SARS-CoV-2 Infection
Several studies have shown that neutralizing antibody levels correlate with immune protection from COVID-19 and have estimated the relationship between neutralizing antibodies and protection. However, results of these studies vary in terms of estimates of the level of neutralizing antibodies required for protection. By normalizing antibody titers, we found that study results converge on a consistent relationship between antibody levels and protection from COVID-19. This finding can be useful for planning future vaccine use, determining population immunity, and reducing the global effects of the COVID-19 pandemic.
Journal Article
Predicting neutralization susceptibility to combination HIV-1 monoclonal broadly neutralizing antibody regimens
Combination monoclonal broadly neutralizing antibodies (bnAbs) are currently being developed for preventing HIV-1 acquisition. Recent work has focused on predicting in vitro neutralization potency of both individual bnAbs and combination regimens against HIV-1 pseudoviruses using Env sequence features. To predict in vitro combination regimen neutralization potency against a given HIV-1 pseudovirus, previous approaches have applied mathematical models to combine individual-bnAb neutralization and have predicted this combined neutralization value; we call this the combine-then-predict (CP) approach. However, prediction performance for some individual bnAbs has exceeded that for the combination, leading to another possibility: combining the individual-bnAb predicted values and using these to predict combination regimen neutralization; we call this the predict-then-combine (PC) approach. We explore both approaches in both simulated data and data from the Los Alamos National Laboratory’s Compile, Neutralize, and Tally NAb Panels repository. The CP approach is superior to the PC approach when the neutralization outcome of interest is binary (e.g., neutralization susceptibility, defined as inhibitory 80% concentration < 1 μg/mL). For continuous outcomes, the CP approach performs nearly as well as the PC approach when the individual-bnAb prediction algorithms have strong performance, and is superior to the PC approach when the individual-bnAb prediction algorithms have poor performance. This knowledge may be used when building prediction models for novel antibody combinations in the absence of in vitro neutralization data for the antibody combination; this, in turn, will aid in the evaluation and down-selection of these antibody combinations into prevention efficacy trials.
Journal Article