Finding vaccine-induced immune response biomarkers that predict vaccine-protection against HIV-1 and other signi?cant pathogen infection, and understanding their role as mechanisms of protection, is an essential part of vaccine research. We distinguish three stages in immune correlates studies. The ?rst stage deals with measurement of immune response and may involve experimental design. The second stage performs preprocessing of immune response variables obtained in the ?rst stage to form composite immune response variables. The third stage examines the association between clinical outcome and immune response variables. We will develop novel statistical methods for each stage in order to increase the signal- to-noise ratio in immune response measurement, create immune response scores with maximum signal diversity, and increase the power of hypothesis testing by using change point regression model.

Public Health Relevance

This project aims to improve the power of immune correlates studies by developing new and improved methods for all three stages of immune correlates studies: measuring immune responses, preprocessing immune response variables, and identifying immune responses associated with HIV-1 infection/transmission.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI122991-02
Application #
9230341
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Gezmu, Misrak
Project Start
2016-03-01
Project End
2021-02-28
Budget Start
2017-03-01
Budget End
2018-02-28
Support Year
2
Fiscal Year
2017
Total Cost
$316,066
Indirect Cost
$136,483
Name
Fred Hutchinson Cancer Research Center
Department
Type
Other Domestic Non-Profits
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Kiyaga, Charles; Urick, Brittany; Fong, Youyi et al. (2018) Where have all the children gone? High HIV prevalence in infants attending nutrition and inpatient entry points. J Int AIDS Soc 21:
Fong, Youyi; Halloran, M Elizabeth; Park, Jin Kyung et al. (2018) Efficacy of a bivalent killed whole-cell cholera vaccine over five years: a re-analysis of a cluster-randomized trial. BMC Infect Dis 18:84
Moodie, Zoe; Juraska, Michal; Huang, Ying et al. (2018) Neutralizing Antibody Correlates Analysis of Tetravalent Dengue Vaccine Efficacy Trials in Asia and Latin America. J Infect Dis 217:742-753
Urick, Brittany; Fong, Youyi; Okiira, Christopher et al. (2018) Rapid Serological Tests Ineffectively Screen for HIV Exposure in HIV-Positive Infants. J Acquir Immune Defic Syndr 77:331-336
Fong, Youyi; Shen, Xiaoying; Ashley, Vicki C et al. (2018) Modification of the Association Between T-Cell Immune Responses and Human Immunodeficiency Virus Type 1 Infection Risk by Vaccine-Induced Antibody Responses in the HVTN 505 Trial. J Infect Dis 217:1280-1288
Fong, Youyi; Huang, Ying; Lemos, Maria P et al. (2018) Rank-based two-sample tests for paired data with missing values. Biostatistics 19:281-294
Mwenda, Reuben; Fong, Youyi; Magombo, Termson et al. (2018) Significant Patient Impact Observed Upon Implementation of Point-of-Care Early Infant Diagnosis Technologies in an Observational Study in Malawi. Clin Infect Dis 67:701-707
Murphy, Sean C; Duke, Elizabeth R; Shipman, Kelly J et al. (2018) A Randomized Trial Evaluating the Prophylactic Activity of DSM265 Against Preerythrocytic Plasmodium falciparum Infection During Controlled Human Malarial Infection by Mosquito Bites and Direct Venous Inoculation. J Infect Dis 217:693-702
McGuire, Erin P; Fong, Youyi; Toote, Christopher et al. (2018) HIV-Exposed Infants Vaccinated with an MF59/Recombinant gp120 Vaccine Have Higher-Magnitude Anti-V1V2 IgG Responses than Adults Immunized with the Same Vaccine. J Virol 92:
Fong, Youyi; Di, Chongzhi; Huang, Ying et al. (2017) Model-robust inference for continuous threshold regression models. Biometrics 73:452-462

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