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Principal Investigator: Margaret Juliana McElrath
Organization: FRED HUTCHINSON CANCER CENTER
Fiscal Year: 2024
Award: $28,707,507
Funding agency: National Institute of Allergy and Infectious Diseases
The overall goal of the Laboratory Center (LC) is to provide the leadership, structure, oversight and execution of
high-quality, state-of-the-art laboratory-based research studies on behalf of the HIV Vaccine Trials Network
(HVTN) that will accelerate the development of a safe and efficacious HIV vaccine. Within this framework, the
LC will also contribute to developing other strategies to prevent HIV (e.g., immune prophylaxis), as well as to
advancing vaccines to prevent M. tuberculosis (Mtb) and other infections of public health importance.
For more than a decade, our LC has directed HVTN laboratory studies through the application of innovative
science and a rigorous lab quality management program. We have overseen the clinical and largely performed
the specialized lab studies globally to broadly define the adaptive, and when relevant, the innate and mucosal
immune responses induced by candidate HIV vaccines tested from first-in-human to large-scale efficacy trials.
We have determined how prime-boost combinations, delivery route and schedule can impact these responses.
The development and use of validated and qualified assays have enabled reliable quantitative assessments and
direct comparisons of functions and specificities across different vaccine platforms. This unique capability in the
field has informed go/no-go decision-making and prioritization of vaccine candidates and specific regimens to
advance to large-scale testing. Our HVTN LC has been at the forefront to define experimentally the correlates
of risk and protection induced by vaccination, and potential explanations for failed or modest efficacy in the Step
Study, HVTN 505, and the RV144 Thai Trial. The LC is now poised to lead lab investigations in five ongoing
global phase 2b/3 HVTN vaccine and HVTN/HPTN immune prophylaxis studies. Through these efforts, the LC
has elevated the standards and feasibility of conducting groundbreaking studies in human immunology in the
global setting and enriched its science through a wide network of collaborations.
Over the next seven years, we propose to build upon and enhance our current scientific and operational
infrastructure to execute innovative HVTN studies in a good clinical laboratory practice (GCLP) setting that will
provide unambiguous measurements of vaccine immunogenicity, vaccine and monoclonal antibody efficacy and
insight into correlates of protection (Aims 1, 3, 4) in adults and children (when indicated). To improve monitoring
tools, we will continue to develop, optimize and validate assays that can reveal the broad range and distribution
of immune functions that candidate agents elicit and in additional compartments beyond blood (Aims 2, 5). We
will embrace collaborations among the larger HIV, TB and immunology fields to enhance these efforts (Aim 6)
and will continue to provide leadership and expertise to facilitate investigations with other HIV clinical trials and
vaccine networks. Headquartered at FHCRC, the Laboratory Center will integrate its activities seamlessly with
the HVTN Leadership and Operations Center and the Statistical and Data Management Center, and
cooperatively with the DAIDS Vaccine Clinical Branch.
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