Building on the skill and expertise of the HVTN Laboratory Center in testing the immunogenicity of HIV vaccines, the McElrath laboratory has initiated collaborations to assess immune responses to candidate malaria and tuberculosis vaccines in conjunction with several partners. The tools and methods developed over the past 15 years by the Laboratory Center readily transfer to assessing these diseases, which are major health burdens in the areas most affected by the HIV epidemic and significantly contribute to morbidity in co-infected patients. Identifying an effective vaccine for these diseases will have a dramatic social, fiscal and health impact in these regions.
The overarching goal of the Scripps Consortium for HIV/AIDS Vaccine Development (CHAVD) is to develop a sequential HIV vaccine regimen that induces sustained protective levels of broadly neutralizing antibodies (bnAbs) in humans. Such antibodies provide complete protection against HIV infection in preclinical models. A second major goal is to generate immunogens that induce protective non-neutralizing antibody (nnAb) responses that can either act alone or augment the protective activity of bnAb responses. To support this translational effort, Dr. McElrath leads the Clinical Trials Sample Analysis Unit within the CHAVD, as well as serving on the scientific steering committee. The McElrath laboratory leverages its expertise in conducting high-quality laboratory studies of HVTN vaccine candidates to conduct selective, specialized immunologic analyses on study participant specimens from clinical trials evaluating CHAVD immunogens in order to accelerate iterative development of HIV vaccine candidates within the consortium.
The Infectious Diseases Clinical Research Consortium (IDCRC) and Vaccine and Treatment Evaluation Units (VTEUs) work in tandem with the National Institute of Allergy and Infectious Diseases (NIAID) as a coordinated national and global network of scientific experts working to develop and test vaccines and other therapies to combat infectious diseases, particularly to respond rapidly to newly emerging infectious disease threats. Dr. McElrath is a member of the IDCRC leadership group and co-director of the IDCRC’s Laboratory Operations Unit (LOU). The LOU links with the VTEUs to provide laboratory services for studies, implements the sharing and distribution of samples and study-related laboratory data across the IDCRC and approved outside partners, and develops and implements ancillary studies to support IDCRC clinical research.
In response to the newly emerging threat of COVID-19, Dr. McElrath quickly moved to establish an observational cohort in the Seattle area to collect samples which could help researchers gain an understanding of how the immune system works in response to COVID. This knowledge will enable us to find better ways to prevent COVID and improve vaccines and treatment.
This cohort focuses on individuals who have already contracted COVID-19 or are at higher risk for exposure, such as people living with someone who has COVID, front-line workers and first responders. It aims to answer two key questions about SARS-CoV-2: How does the immune system react before symptoms develop? And do people who have recovered from COVID-19 develop immunity?
Approximately 5-10% of individuals with documented HIV-1 infection fail to experience CD4+ T-cell depletion, immunosuppression, and opportunistic infections after a decade of diagnosis. These individuals, designated long-term non-progressors (LTNP), are a heterogeneous group in which various genetic, immune and viral factors may delineate long-term prognosis. By recognizing the relative contribution of each of these factors to the LTNP phenotype, we can derive insight into the pathogenic mechanisms of HIV-1 disease and the protective mechanisms that prevent progression. Thus, we are conducting longitudinal, observational studies to examine immune responses in a cohort of LTNP. The goal of these studies is primarily to determine the role of virus-specific cytotoxic T-cell lymphocyte (CTL) activity versus CCR5 expression on viral load, the role of T helper responses in sustaining CTL responses, the patterns of epitope recognition associated with alterations in viral load, and the viral load in mucosal compartments in comparison to peripheral blood. By understanding these mechanisms in LTNP, we can apply this knowledge to designing preventative measures against HIV-1 disease and progression.
Fast facts about the LTNP cohort: