Human Immunodeficiency Virus
Barbara Lohman-Payne, Ph.D., Assistant Research Professor
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.
Rui Liu, Assistant Research Professor
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.