Biology subjects

Lehman, D. A.

Publications and source records attributed to Lehman, D. A..

3 recordsLinked to original sources

bioRxiv2026

Modeling HIV infection, treatment, rebound, and intervention in human immune organoids

Targeting the HIV-infected reservoir in lymphoid tissues (LT) will be critical to developing a cure for people living with HIV (PLWH). LT explants used to study HIV infection enable the evaluation of human-specific disease progression and treatment response; however, their short lifespan makes it challenging to assess long-term treatment interventions. We therefore established an immune organoid model of HIV infection using human tonsil or spleen cells, demonstrating productive HIV infection and viral integration into CD4+ T cells. Treatment with a protease inhibitor fully suppressed ongoing viral production, with virologic rebound occurring within days of treatment interruption. The transfer of healthy allogeneic NK cells to target the reservoir upon treatment interruption reduced the number of infected cells, intact viral genomes, and production of de novo infectious viral particles. Adoption of this immune organoid platform will accelerate the evaluation of cure-based strategies to eliminate the HIV reservoir in tissues for PLWH.

immunology↗

bioRxiv2023

Elevated binding and functional antibody responses to SARS-CoV-2 in infants versus mothers

Infant antibody responses to viral infection can differ from those in adults. However, data on the specificity and function of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in infants, and direct comparisons between infants and adults are limited. We characterized antibody binding and functionality in convalescent plasma from postpartum women and their infants infected with SARS-CoV-2 from a vaccine-naive prospective cohort in Nairobi, Kenya. Antibody titers against SARS-CoV-2 Spike, receptor binding domain and N-terminal domain, and Spike-expressing cell-surface staining levels were significantly higher in infants than in mothers. Plasma antibodies from mothers and infants bound to similar regions of the Spike S2 subunit, including the fusion peptide (FP) and stem helix-heptad repeat 2. However, infants displayed higher antibody levels and more consistent antibody escape pathways in the FP region compared to mothers. Finally, infants had significantly higher levels of antibody-dependent cellular cytotoxicity (ADCC), though, surprisingly, neutralization titers between infants and mothers were similar. These results suggest infants develop distinct SARS-CoV-2 binding and functional antibody repertoires and reveal age-related differences in humoral immunity to SARS-CoV-2 infection that could be relevant to protection and COVID-19 disease outcomes.

immunology↗

bioRxiv2022

Distinct antibody responses to endemic coronaviruses pre- and post-SARS-CoV-2 infection in Kenyan infants and mothers

Pre-existing antibodies that bind endemic human coronaviruses (eHCoVs) can cross-react with SARS-CoV-2, the betacoronavirus that causes COVID-19, but whether these responses influence SARS-CoV-2 infection is still under investigation and is particularly understudied in infants. In this study, we measured eHCoV and SARS-CoV-1 IgG antibody titers before and after SARS-CoV-2 seroconversion in a cohort of Kenyan women and their infants. Pre-existing eHCoV antibody binding titers were not consistently associated with SARS-CoV-2 seroconversion in infants or mothers, though we observed a very modest association between pre-existing HCoV-229E antibody levels and lack of SARS-CoV-2 seroconversion in infants. After seroconversion to SARS-CoV-2, antibody binding titers to endemic betacoronaviruses HCoV-OC43 and HCoV-HKU1, and the highly pathogenic betacoronavirus SARS-CoV-1, but not endemic alphacoronaviruses HCoV-229E and HCoV-NL63, increased in mothers. However, eHCoV antibody levels did not increase following SARS-CoV-2 seroconversion in infants, suggesting the increase seen in mothers was not simply due to cross-reactivity to naively generated SARS-CoV-2 antibodies. In contrast, the levels of antibodies that could bind SARS-CoV-1 increased after SARS-CoV-2 seroconversion in both mothers and infants, both of whom are unlikely to have had a prior SARS-CoV-1 infection, supporting prior findings that SARS-CoV-2 responses cross-react with SARS-CoV-1. In summary, we find evidence for increased eHCoV antibody levels following SARS-CoV-2 seroconversion in mothers but not infants, suggesting eHCoV responses can be boosted by SARS-CoV-2 infection when a prior memory response has been established, and that pre-existing cross-reactive antibodies are not strongly associated with SARS-CoV-2 infection risk in mothers or infants.

microbiology↗