Biology subjects

Heredia, A.

Publications and source records attributed to Heredia, A..

3 recordsLinked to original sources

bioRxiv2024

A Comprehensive Engineering Strategy Improves Potency and Manufacturability of a Near Pan-neutralizing Antibody Against HIV

Anti-HIV envelope broadly neutralizing antibodies (bnAbs) are alternatives to conventional antiretrovirals with the potential to prevent and treat infection, reduce latent reservoirs, and/or mediate a functional cure. Clinical trials with "first generation" bnAbs used alone or in combination show promising antiviral effects but also highlight that additional engineering of "enhanced" antibodies will be required for optimal clinical utility, while preserving or enhancing cGMP manufacturing capability. Here we report the engineering of an anti-CD4 binding-site (CD4bs) bnAb, N49P9.3, purified from the plasma of an HIV elite-neutralizer. Through a series of rational modifications we produced a variant that demonstrates: enhanced potency; superior antiviral activity in combination with other bnAbs; low polyreactivity; and longer circulating half-life. Additional engineering for manufacturing produced a final variant, eN49P9, with properties conducive to cGMP production. Overall, these efforts demonstrate the feasibility of developing enhanced anti-CD4bs bnAbs with greatly improved antiviral properties as well as potential translational value.

bioengineering↗

bioRxiv2024

Genetic signatures in the highly virulent subtype B HIV-1 conferring immune escape to V1/V2 and V3 broadly neutralizing antibodies

HIV-1 is considered to become less susceptible to existing neutralizing antibodies over time. Our study on the virulent B (VB) HIV-1 identified genetic signatures responsible for immune escape from broadly neutralizing antibodies (bNAbs) targeting V1/V2 and V3 glycan epitopes. We found that the absence of N295 and N332 glycans in the high mannose patch, which are crucial for neutralization by V3 glycan bNAbs and are typically conserved in subtype B HIV-1, is a notable feature in more than half of the VB variants. Neutralization assays confirmed that the loss of these two glycans in VB HIV-1 leads to escape from V3 glycan bNAbs. Additionally, all VB variants we investigated have an insertion in V2, contributing to immune escape from V1/V2 bNAbs PG9 and PG16. These findings suggest potential co-evolution of HIV-1 virulence and antigenicity, underscoring the need to monitor both the pathogenicity and neutralization susceptibility of newly emerged HIV-1 strains.

microbiology↗

bioRxiv2022

3D (x-y-t) Raman imaging of tomato fruit cuticle: microchemistry during development

The cuticle of tomato fruits was studied in-situ using Confocal Raman Microscopy. Microsections from cuticles isolated at different developmental stages were scanned to reveal the distribution of cuticle components with a spatial resolution of 342 nm by univariate and multivariate data analysis. From the three main components, cutin, polysaccharides and aromatics, the latter one exhibit the strongest Raman scattering intensity. Therefore, Raman imaging opened the view on phenolic acids and flavonoids within the cuticle and resulted in three schematic cuticle models depicting development. At the earliest stage of development, which corresponded to the procuticle layer, phenolic acids were found across the entire cuticle. Based on a mixture analysis with reference component spectra, the phenolic acids were identified as mainly esterified p-coumaric acid together with free p-hydroxybenzoic acid. Later in development, during the cell expansion period of growth, phenolic acids accumulated in an outermost layer of the cuticle and in the middle region of the pegs. In these stages of development cellulose and pectin were appeared towards the epidermal layer, where later during ripening the flavonoid impregnation started. In the first ripening stage chalconaringenin was observed, while methoxylated chalcones were chosen by the algorithm to fit the mature cuticle spectra. The co-location with carbohydrates and esterified p-coumaric acid and methoxylated chalconaringenin suggest that they link polysaccharide and cutin domains. Within the cutin matrix, aromatics confer mechanical and thermal functions, while the outermost phenolic acid layer displays UV-B protection of the plant tissue. One-sentence summaryNew insights into the distribution of cutin, carbohydrates and phenolics along cross sections of green and mature tomato fruit cuticles by Raman mapping and multivariate data analysis.

biophysics↗