Odessa Marks Lacsina, PhD


Nominated From: University of Washington

Research Site: Kenya

Research Area: HIV/AIDS; Vaccination

Primary Mentor: Dr. Carey Farquhar

Research Project

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.

Research Significance

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.





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