HIV vaccine research is an essential part of the fight against the global HIV/AIDS pandemic. Finding immune responses that predict vaccine-induced protection, or "immune correlates", has a great impact on the HIV vaccine research, as it sheds light on the mechanism of the protection and helps improve vaccine design. This proposal is composed of two sets of statistical methods for improving the statistical power of identifying immune correlates.
Aim 1 develops methods that will help investigators choose the best immune response positivity criteria. A positivity criterion for an immune response is a set of rules that classifies a subject's response as either negative or positive. A good positivity criteron can be used to help define immune response variables to assess their correlation with infection status. The proposal takes a decision theoretic approach to choosing positivity criteria that balance the false positive rates and the false negative rates.
Aim 2 develops analytical methods for an important technology used to measure immune responses: the multiplex bead array (MBA). A key step in processing MBA data is to fit a concentration-response curve using data from standard samples which contain known amounts of analytes to be measured. Poor curve fits lead to large measurement error, which will dampen the statistical association between the infection status and the observed immune responses. The proposal examines two issues in curve fitting. First, two approaches for handling the mean-variance relationship of the observed fluorescence intensity are compared: weighted least squares and un-weighted least squares on log-transformed fluorescence intensity. Second, three models for the shape of the concentration-response curves are compared: four-parameter logistic model, five-parameter logistic model, and a semi-parametric model.

Public Health Relevance

HIV vaccine research is an essential part of the fight against the global HIV/AIDS pandemic. Finding immune responses that predict vaccine-induced protection has a great impact on the HIV vaccine research, as it sheds light on the mechanism of the protection and helps improve vaccine design. To improve our ability to find immune responses that correlate with vaccine-induced protection, this proposal develops novel statistical methods for the design and analysis of immune-correlates studies in preventative HIV vaccine efficacy trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Research Grants (R03)
Project #
1R03AI104370-01
Application #
8467361
Study Section
HIV/AIDS Vaccines Study Section (VACC)
Program Officer
Gezmu, Misrak
Project Start
2013-01-01
Project End
2014-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
1
Fiscal Year
2013
Total Cost
$88,000
Indirect Cost
$38,000
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Fong, Youyi; Sebestyen, Krisztian; Yu, Xuesong et al. (2013) nCal: an R package for non-linear calibration. Bioinformatics 29:2653-4