D'Angelo, H. | Search bioRxiv

bioRxiv2026

Atomic Layering Thermostable Antigen and Adjuvant (ALTA(R)) platform provides unique antigen delivery system through controlled release to improve immune response to vaccination

Prophylactic vaccines are commonly delivered using a multi-dose regimen with the goal of generating potent, durable protection against a specific pathogen. However, the requirement for multiple administrations can impede patient adherence and reduce overall protection. Designing a single-shot vaccine without compromising efficacy could significantly improve vaccine adherence and performance. Previously, it has been shown that atomic-layer deposition (ALD) of alumina (Al2O3) can be applied to spray dried, thermostabilized antigen-containing powders to produce alumina-coated vaccine particles that, when compared to a liquid control, elicit improved humoral immunity with response kinetics controlled by ALD-coat thickness. However, previous studies have not defined the particle release/antigen delivery profile of ALD-coated vaccines. The studies in this manuscript were designed to investigate how the kinetics of antigen release from ALD-coated vaccines impacts the timing and magnitude of the immune response relative to single- and multi-dose liquid vaccine regimens using two distinct antigens, Ovalbumin and the HIV-1 envelope trimer, N332-GT5 gp140. By combining longitudinal in vivo imaging and immunological readouts, we demonstrate that ALD-coated vaccines exhibit tunable, variable-rate release and deliver antigen in a unique, prolonged manner that results in an improved immune response to single-shot vaccination for difficult to target pathogens, such as HIV-1. Furthermore, using in vitro analytical methods, we confirmed the ability of our Atomic Layering and Thermostable Antigen and Adjuvant (ALTA(R)) platform to impart thermostability upon the N332-GT5 gp140 antigen, a clinically relevant HIV-1 immunogen, indicating the potential for ALTA(R) formulation to generate thermostable, single-dose vaccine products. Highlights- ALTA(R) microparticles provide sustained antigen delivery with variable release rates, which can be controlled by altering ALD-coat thickness - Sustained antigen release from thermostable, spray-dried ALTA(R) vaccine products impacts kinetics of humoral and cellular responses, and improves antigen-specific immunogenicity compared to single administration of liquid vaccine - ALTA(R) formulation imparts vaccine thermostability through spray-drying and ALD-coating to clinically relevant HIV-1 Env antigen, N332-GT5 gp140

immunology↗

bioRxiv2021

Preconditioning by voluntary wheel running attenuates later neuropathic pain via Nrf2 antioxidant signaling in rats

Animal and human studies have shown that exercise prior to nerve injury prevents later chronic pain, but the mechanisms of such preconditioning remain elusive. Given that exercise acutely increases formation of free radicals, triggering antioxidant compensation, we hypothesized that voluntary running preconditioning would attenuate neuropathic pain by supporting redox homeostasis after sciatic nerve injury in male and female rats. We show that 6 weeks of voluntary wheel running suppresses neuropathic pain development induced by chronic constriction injury (CCI) across both sexes. This protection was associated with reduced nitrotyrosine immunoreactivity--a marker for peroxynitrite--at the sciatic nerve injury site. Our data suggest that prior voluntary wheel running does not reduce production of peroxynitrite precursors, as expression levels of inducible nitric oxide synthase and NADPH oxidase 2 were unchanged. Instead, voluntary wheel running increased superoxide scavenging by elevating expression of superoxide dismutases 1 and 2. Prevention of neuropathic pain was further associated with activation of the master transcriptional regulator of the antioxidant response, nuclear factor E2-related factor 2 (Nrf2). Six weeks of prior voluntary wheel running increased Nrf2 nuclear translocation at the sciatic nerve injury site; in contrast, 3 weeks of prior wheel running, which failed to prevent neuropathic pain, had no effect on Nrf2 nuclear translocation. The protective effects of prior voluntary wheel running were mediated by Nrf2, as suppression was abolished across both sexes when Nrf2 activation was blocked during the running phase. This study provides insight into the mechanisms by which physical activity may prevent neuropathic pain.

neuroscience↗