Atomic Layering Thermostable Antigen and Adjuvant (ALTA^®) platform provides unique antigen delivery system through...

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^®) platform to impart thermostability upon the N332-GT5 gp140 antigen, a clinically relevant HIV-1 immunogen, indicating the potential for ALTA^® formulation to generate thermostable, single-dose vaccine products.