Biology subjects

Saouaf, O.

Publications and source records attributed to Saouaf, O..

3 recordsLinked to original sources

bioRxiv2026

Sustained Delivery of a Shingles Subunit Vaccine Overcomes Age-Related Declines in Humoral and Cellular Immunity Relative to Shingrix

The global aging population faces heightened vulnerability to infectious diseases due to immunosenescence, which diminishes the potency, durability, and breadth of vaccine-induced immunity. While the leading shingles vaccine, Shingrix(R), provides protection against herpes zoster virus for adults aged 50 and older, it is often associated with severe local and systemic reactogenicity, which limits vaccine compliance. Here, we report an injectable polymer-nanoparticle (PNP) hydrogel platform for the sustained delivery of a shingles subunit vaccine to enhance immune responses while mitigating reactogenicity in aged mice. Hydrogel-based vaccination elicited significantly more potent and durable humoral immune responses than Shingrix(R), while inflammatory cytokine levels remained below the limit of detection. Moreover, aged mice vaccinated with the hydrogel-based vaccine exhibited robust antigen-specific cellular immune responses. These findings demonstrate that controlling the temporal presentation of vaccine components can overcome age-associated declines in immune responsiveness without inducing excessive inflammatory signaling. By decoupling immunogenicity from reactogenicity, our hydrogel-based delivery strategy offers a promising approach to improve both the efficacy and tolerability of subunit vaccines for the elderly and may be broadly applicable to other vaccines targeting aging populations.

immunology↗

bioRxiv2023

Saponin Nanoparticle Adjuvants Incorporating Toll-Like Receptor Agonists Improve Vaccine Immunomodulation

Over the past few decades, the development of potent and safe immune-activating adjuvant technologies has become the heart of intensive research in the constant fight against highly mutative and immune evasive viruses such as influenza, SARS-CoV-2, and HIV. Herein, we developed a highly modular saponin-based nanoparticle platform incorporating toll-like receptor agonists (TLRas) including TLR1/2a, TLR4a, TLR7/8a adjuvants and their mixtures. These various TLRa-SNP adjuvant constructs induce unique acute cytokine and immune-signaling profiles, leading to specific Th-responses that could be of interest depending on the target disease for prevention. In a murine vaccine study, the adjuvants greatly improved the potency, durability, breadth, and neutralization of both COVID-19 and HIV vaccine candidates, suggesting the potential broad application of these adjuvant constructs to a range of different antigens. Overall, this work demonstrates a modular TLRa-SNP adjuvant platform which could improve the design of vaccines for and dramatically impact modern vaccine development. TeaserSaponin-TLRa nanoadjuvants provide distinct immune signatures and drive potent, broad, durable COVID-19 and HIV vaccine responses.

bioengineering↗

bioRxiv2021

Injectable Nanoparticle-Based Hydrogels Enable the Safe and Effective Deployment of Immunostimulatory CD40 Agonist Antibodies

When properly deployed, the immune system can eliminate deadly pathogens, eradicate metastatic cancers, and provide long-lasting protection from diverse diseases. Unfortunately, realizing these remarkable capabilities is inherently risky as disruption to immune homeostasis can elicit dangerous complications or autoimmune disorders. While current research is continuously expanding the arsenal of potent immunotherapeutics, there is a technological gap when it comes to controlling when, where, and how long these drugs act on the body. Here, we explore the ability of a slow-releasing injectable hydrogel depot to reduce the problematic dose-limiting toxicities of immunostimulatory CD40 agonist (CD40a) while maintaining their potent anti-cancer efficacy. We leverage a previously described polymer-nanoparticle (PNP) hydrogel system that exhibits shear-thinning and yield-stress properties that we hypothesized would improve locoregional delivery of the CD40a immunotherapy. Using PET imaging, we demonstrate that prolonged hydrogel-based delivery redistributes CD40a exposure to the tumor and the tumor draining lymph node (TdLN), thereby reducing weight loss, hepatotoxicity, and cytokine storm associated with standard treatment. Moreover, CD40a-loaded hydrogels mediate improved local cytokine induction in the TdLN and improve treatment efficacy in the B16F10 melanoma model. PNP hydrogels, therefore, represent a facile, drug-agnostic method to ameliorate immune-related adverse effects and explore locoregional delivery of immunostimulatory drugs.

bioengineering↗