senior scientist VitriVax, Inc. Boulder, Colorado, United States
Introduction/Rationale: 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.
