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

Abstract

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.