HIV

 

Human Immunodeficiency Virus

Barbara Lohman-Payne, Ph.D., Assistant Research Professor
Dr. Lohman-Payne’s team is particularly interested in understanding how in utero Human Immunodeficiency Virus (HIV) exposure affects the immune system in early life. Dr. Lohman-Payne has long-standing collaborations with investigators at the University of Nairobi (Link to UoN-Ruth Nduati’s page) and University of Washington (Link to UW-Grace John Stewart’s page) where a groundbreaking randomized controlled trial was conducted that determined the risk of HIV acquisition attributable to breast milk and that, despite ingestion of gallons of HIV-infected milk, 70% of breastfeeding infants remain HIV uninfected, even in the absence of antiretroviral therapy. As availability of antiretroviral treatment increases globally, more HIV-1 infected women will have access to drugs to prevent mother-to-child transmission and the numbers of HIV-1 exposed uninfected (HIV EU) children will continue to increase.

 

HIV EU infants make up a unique population within the broader category of HIV exposed individuals. The majority of HIV EU individuals are adults and who remain persistently HIV seronegative after repeated exposure to HIV-1 from their seropositive partner or from commercial sex work. HIV EU infants, in contrast, have prolonged antigen exposure in utero to maternal HIV as well as to other chronic infectious diseases such as cytomegalovirus, tuberculosis and malaria. This in utero exposure is concomitant with thymic T cell development. After birth, the infant is immunized with a series of standardized vaccines, and exposed to a wide array of environmental antigens. Infants born to HIV-1 infected women are at increased risk of morbidity and mortality the first years of life compared to infants born to HIV uninfected women. What component of this increased risk is due to being born into an HIV-affected household, and how much is due to immunologic modeling in utero is the subject of continued research in the LVIP lab.

One avenue of our translational research aims to determine the impact of in utero HIV-1 exposure on infant immunity to vaccinations and co-infections by dissecting the infant immune repertoire present at birth in the context of maternal HIV-1 infection and how the infant T cell repertoire changes following early life exposures compared to infants born to the HIV-1 uninfected women of similar socio-economic status. Infant T cell repertoire analysis combines quantitative PCR to determine relative frequency of T cell receptor  chain families with deep sequencing (LINK TO URI GSC) of the CDR3 region to evaluate clonal diversity within each family. Potential correlates of TCR diversity under evaluation include the cytokine milieu and T cell activation state present at birth and the early responses to birth vaccines.

Barbara
Rui Liu, Assistant Research Professor
We recently discover a new immune escape mechanism that may help viruses escape from immune detection, which might compromise vaccine efficacy. Viruses that cause chronic infection in human contain higher numbers of T cell epitopes whose TCR-facing amino acids are identical to those of numerous peptides from the human proteome.  We postulate that viruses that incorporate such human-like epitopes may exploit host tolerance to avoid or suppress effector responses. In order to predict these human-like epitopes, we developed an immunoinformatics tool, JanusMatrix.

 

Using JanusMatrix, we have identified T cell epitopes in H7N9 influenza HA protein that are highly conserved with human genome epitopes, and these epitopes possess low immunogenicity, activate natural Tregs and suppress bystander effector T cell responses in vitro. The human like T cell epitopes may contribute to the delayed, low titer of H7N9 hemagglutination inhibiting antibody responses and diminished seroconversion rates that have been observed in human infections and unadjuvanted H7 HA vaccination clinical trials. We also turned our attention to HIV-1 and found several such epitopes in the envelope (Env) protein of HIV-1, one of which was included in both the HIV-1 E and HIV-1 B Env antigens that were used in the ‘moderately effective’ HIV RV144 trial in Thailand. Validation of the immunological role of these epitopes is in the process.

Rui

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  • February 19, 2016

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    This past week at iCubed, Dr. Barbara Lohman Payne received a new title of Associate Research Professor. Barbara joined iCubed and URI as a Research Assistant Professor in 2013, with the Laboratory of Viral Immunity and Pathogenesis. Dr. Lohman-Payne’s area of research is viral immunopathology, with special interest in the impact of HIV exposure in ...
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