Biology subjects

Jimenez, L. E.

Publications and source records attributed to Jimenez, L. E..

3 recordsLinked to original sources

bioRxiv2026

Title: Combinatorial bnAb and T Cell Immunization Enhances Post-Infection Control of SHIVSF162p3 Viremia in Rhesus Macaques

An ideal HIV-1 vaccine should provide broad protection against most HIV-1 variants, control early dissemination of infected cells after virus acquisition, and avoid the risk that vaccine-induced, HIV-specific CD4+ T cells serve as targets for viral transmission. In this study, we modeled this complex host-virus interaction in rhesus macaques challenged with a single high dose of SHIVSF162p3. Specifically, we evaluated the impact of T cell immunization with a human adenovirus-5-based candidate vaccine encoding an SIV Gag-Tat fusion (AdHu5SIVGag/Tat) alongside a partially protective, limiting dose of the broadly neutralizing antibody (bnAb) PGT121. Immunization with AdHu5SIVGag/Tat elicited Gag-specific CD4+ and CD8+ T cell responses in PBMC and mucosal tissue. T cell vaccination did not affect PGT121-mediated protection against SHIVSF162p3 acquisition. However, independently of vaccination, constitutively activated CD4+4{beta}7+Ki-67+ T cells in rectal tissue attenuated PGT121-mediated protection. Crucially, a unique pattern of post-infection control of SHIVSF162p3 viremia emerged in AdHu5SIVGag/Tat-immunized, PGT121-treated animals, characterized by an increased eclipse phase, lower peak viremia, and a late-phase decay in steady-state viremia. These results suggest potential synergy between bnAbs and AdHu5SIVGag/Tat-induced antiviral T cell responses, with significant implications for HIV-1 vaccine development and early interventions following infection.

immunology↗

bioRxiv2022

Complex scaffold remodeling in plant triterpene biosynthesis

Triterpenes with complex scaffold modifications are widespread in plants yet little is known regarding biosynthesis. Limonoids are an exemplary family that includes the bitter taste in citrus (e.g., limonin) and the active constituents in neem oil, a widely used bioinsecticide (e.g., azadirachtin). Despite limonoid commercial value, a complete biosynthetic route has not been described. Here, we report the discovery of 22 enzymes that catalyze 12 unique reactions including the 4-carbon scission and furan installation that are a signature of the limonoid family and a pair of sterol isomerases previously unknown in plants. This gene set is then used for the total biosynthesis of kihadalactone A and azadirone in a heterologous plant. These results enable access to valuable limonoids and provide a template for discovery and reconstitution of triterpene biosynthetic pathways in plants that require multiple skeletal rearrangements and oxidations.

biochemistry↗

bioRxiv2021

Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM

In BriefHerein, we evaluated the immunogenicity of several BG505 SOSIP-based HIV Env immunogens in the rhesus macaque animal model using a combination of serology and biophysical approaches. We applied electron cryo-microscopy for high-resolution mapping of elicited polyclonal antibody responses, which provided detailed insights into the binding modes of the most common classes of antibodies elicited by BG505 SOSIP immunogens as well as the critical differences in immunogenicity that can occur as a consequence of engineered stabilizing mutations and partial glycan occupancy at different sites. SummaryEngineered ectodomain trimer immunogens based on BG505 envelope glycoprotein are widely utilized as components of HIV vaccine development platforms. In this study, we used rhesus macaques to evaluate the immunogenicity of several stabilized BG505 SOSIP constructs both as free trimers and presented on a nanoparticle. We applied a cryoEM-based method for high-resolution mapping of polyclonal antibody responses elicited in immunized animals (cryoEMPEM). Mutational analysis coupled with neutralization assays were used to probe the neutralization potential at each epitope. We demonstrate that cryoEMPEM data can be used for rapid, high-resolution analysis of polyclonal antibody responses without the need for monoclonal antibody isolation. This approach allowed to resolve structurally distinct classes of antibodies that bind overlapping sites. In addition to comprehensive mapping of commonly targeted neutralizing and non-neutralizing epitopes in BG505 SOSIP immunogens, our analysis revealed that epitopes comprising engineered stabilizing mutations and of partially occupied glycosylation sites can be immunogenic. Graphical abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

immunology↗