Biology subjects

Walters, I. R.

Publications and source records attributed to Walters, I. R..

2 recordsLinked to original sources

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↗

bioRxiv2026

Subunit Vaccination Using Atomic Layering Thermostable Antigen and Adjuvant (ALTA(R)) Platform Elicits Enhanced Humoral and Cellular Immune Responses

AbstractCreating effective and thermostable vaccines is of significant relevance for public health. The Atomic Layering Thermostable Antigen and Adjuvant (ALTA(R)) platform combines spray drying to stabilize antigens in a sugar matrix followed by coating with atomic layer deposition (ALD) for temporal control over in vivo release. While these technologies have shown preliminary promise for different vaccine antigens, further characterizations of the immune response to ALTA(R) formulated antigens are still needed. Here, the immune response to ALTA(R) formulated antigens is described and compared to a set of adjuvanted liquid vaccine formulations that included Alhydrogel(R), AddaVax, and Alhydrogel(R)+CpG. The humoral and cell-mediated responses were measured by ELISA and flow cytometry. Increased and lasting antigen-specific antibody titers following administration of ALTA(R) containing ovalbumin (OVA) demonstrated robust and durable humoral response. Furthermore, ALTA(R) injected mice produced both IgG2c and IgG1 indicating a balanced Th1/Th2 response. Importantly, ALTA(R) OVA elicited robust humoral response at lower doses of aluminum than Alhydrogel(R). The most striking difference between ALTA(R) and the liquid vaccine formulations tested was a greater OVA-specific CD8+ T cell response observed at all antigen doses tested. Mechanistically, antigen encapsulation within ALTA(R) particles was critical for antibody production and CD8+ T cell responses as well as antigen capture by antigen-presenting cells (APCs) at the site of injection and draining lymph nodes. To test these concepts in a more physiological application, protein and polysaccharide vaccine antigens derived from a facultative intracellular bacterium Burkholderia pseudomallei, the causative agent of melioidosis, were formulated using the ALTA(R) platform. Compared to liquid vaccine formulations, ALTA(R) immunized mice showed enhanced antigen-specific antibody production and IFN-{gamma} secreting T cell responses using lower adjuvant doses of aluminum and CpG. Overall, ALTA(R) formulated protein and polysaccharide antigens elicited strong humoral and cell-mediated immunity suggesting potential broad applicability of the platform to vaccines against various diseases, including against cancer and infections from intracellular pathogens.

immunology↗