Odessa Marks Lacsina, PhD
Nominated From: University of Washington
Research Site: Kenya
Research Area: HIV/AIDS; Vaccination
Primary Mentor: Dr. Carey Farquhar
Immunologic correlates of sustained responsiveness to measles revaccination in a cohort of HIVpositive Kenyan children on antiretroviral therapy
The proposed study is nested within a larger study based at Kenyatta National Hospital, Nairobi, Kenya in which HIVinfected children on ART were revaccinated for measles when their CD4% reached 15% of total T cells. Serum and PBMCs were collected and frozen at the time of revaccination, one month postrevaccination and one year postrevaccination. Viral load, CD4 count, and CD4% of total T cells will be determined at each time point. At the time of this writing, it is estimated that one year postrevaccination samples will be available from at least 182 participants. Measles specific serum IgG have been measured by ELISA at one year postrevaccination to define the groups of longterm revaccination responders and nonresponders, and all experiments described below will compare PBMCs or serum samples between these two groups.
The overall goal of my project is to define the immunologic correlates that distinguish longterm responders versus non responders to measles revaccination after ART. I hypothesize that nonresponders have a reduced population of memory B cells, associated with starting ART at a later age. I propose to test this hypothesis via the following specific aims:
1. Investigate the differences in the B cell and memory B cell populations between measles revaccination responders and nonresponders.
2. Contrast the serum cytokine profiles of revaccination responders and nonresponders, particularly the overall Th1/Th2 bias.
3. Evaluate the relationship between the age at ART initiation and responsiveness to measles revaccination.
The proposed study represents the first effort to characterize the immunologic correlates of nonresponsiveness to measles revaccination in HIVpositive children on ART in SubSaharan Africa. I am particularly interested to explore the hypothesis that initiation of ART earlier in life leads to durable antimeasles immunity after revaccination. This is in accord with randomized controlled trials and systematic reviews that have determined that initiating ART within the first year of life leads to decreased morbidity and mortality. We project that the results from these studies will comprise a key component of the evidence base used by WHO to formulate guidelines on the revaccination of HIVpositive children on ART. Potential future directions based on this work include the design of prospective studies that investigate the effects of varying age of ART initiation on durable responses to revaccination and comparing the efficacy of different empiric revaccination schedules on maintaining protective immunity. Finally, on a local scale, the proposed research will help build research capacity for our local partner, the University of Nairobi, to use flow cytometric tools to assay immune correlates of disease in future research.