Atomic layering thermostable antigen and adjuvant (ALTA®) provides unique, controlled antigen release to improve immune response to vaccination

Prophylactic vaccines commonly require a multi-dose regimen to achieve robust, durable protection against a specific pathogen. However, poor patient adherence to these regimens reduces overall protection and highlights the need to develop single-shot vaccines without compromising efficacy. Utilizing atomic-layer deposition (ALD) to coat spray-dried, thermostable, antigen-containing microparticles with alumina (Al 2 O 3 ) is one strategy that may enable single-shot vaccination. Previous studies have shown that alumina coated vaccine microparticles can elicit stronger humoral responses than traditional vaccine formulations and the immune response kinetics can be controlled by altering the number of ALD cycles applied. However, the in vivo particle release and antigen delivery profiles of ALD-coated vaccines have yet to be determined. Here, we performed longitudinal in vivo imaging in mice to demonstrate that ALD-coated vaccines exhibit tunable, variable-rate release and deliver antigen in a unique, prolonged manner. We found that the humoral responses elicited by ALD-coated vaccines containing two distinct protein subunit antigens, ovalbumin and N332-GT5 gp140, a germline-targeting HIV-1 immunogen, matched or exceeded single- and multi-dose regimens of traditional vaccine formulations. Furthermore, using in vitro analytical methods, we confirmed that formulation within our atomic layering and thermostable antigen and adjuvant (ALTA®) platform imparts thermostability upon N332-GT5 gp140, a clinically relevant HIV-1 immunogen. These studies provide an in-depth characterization of in vivo particle release and antigen delivery from ALD-coated vaccines, supporting the use of ALTA® formulation to generate thermostable, single-shot vaccine products.