Subunit Vaccination Using Atomic Layering Thermostable Antigen and Adjuvant (ALTA®) Platform Elicits Enhanced Humoral and Cellular Immune Responses 2258445

Abstract

Abstract Introduction Creating effective and thermostable vaccines is of significant relevance for global health. The Atomic Layering Thermostable Antigen and Adjuvant (ALTA®) platform combines spray drying to encapsulate antigens in a sugar matrix for improved thermostability followed by alumina layer coating for temporal control over in vivo release. Given these advantages, understanding the immune response to ALTA® formulated antigens is important. Here, the immune response to ALTA® formulated antigen was described and compared to a set of adjuvanted liquid formulations. In addition, critical attributes of the ALTA® platform driving its immunogenicity were determined. Methods B6 mice were administered OVA antigen formulated with ALTA® platform or liquid adjuvants, including Alhydrogel®, AddaVax™, Alhydrogel®+CpG. The humoral and cell-mediated responses were measured by ELISA and flow cytometry. Fluorescent OVA was utilized to characterize antigen-presenting cells (APCs) at the site of injection and in lymph nodes. Results Increased and lasting antigen-specific antibody titers post administration of ALTA® OVA demonstrated robust and durable humoral response. In contrast to adjuvants, ALTA® injected mice produced both IgG2c and IgG1 indicating a more balanced Th1/Th2 response. Importantly, ALTA® OVA elicited robust humoral response at lower doses of aluminum than Alhydrogel®. At all antigen doses, the magnitude of OVA-specific CD8+ T cell response was significantly higher after ALTA® administration. The adaptive immune response and numbers of OVA+ APCs were lower after injection of placebo ALTA® mixed with OVA in diluent than ALTA® formulated OVA. This result demonstrated that antigen encapsulation contributes to the immunogenicity of the platform. Conclusion ALTA® formulated protein antigen elicits strong humoral and cell-mediated immunity suggesting a potential broad applicability of the platform to vaccines against various diseases, including intracellular infections and cancer. Funding Source The Gates Foundation INV-064824, The Gates Foundation INV-076862 Topic Categories Vaccines and Immunotherapy (VAC)