Developing a Vaccine Platform for a Balanced Mucosal Immune Response (CB11446), Project Report: Year 1

Abstract

Mucosal vaccines can elicit protective immune responses at the infection site of respiratory or aerosolized pathogens. Achieving balanced mucosal and systemic responses is a key challenge in the design of mucosal vaccines, especially in terms of developing a broadly applicable vaccine delivery platform amenable to a wide range of subunit vaccine antigens. The overarching goal of the project entitled “Developing a Vaccine Platform for a Balanced Mucosal Immune Response” is to develop a pathogen-agnostic vaccine platform that elicits robust and balanced mucosal immune responses upon intranasal vaccination, in the context of a nanolipoprotein particle (NLP) platform. In year one, we investigated NLP-based vaccine formulations incorporating select immune adjuvants (Monophosphoryl Lipid A (MPLA), FSL-1, L18-muramyl dipeptide (MDP), and cholesterol-tagged ODN2006 (cCpG)) along with antigens relevant to plague (LcrV), tularemia (IglC), and Ebola virus (GP). We demonstrated the ability to prepare, characterize, and quantify these formulations. We then carried out studies in vivo using a BALB/c mouse model, comparing intranasal and intramuscular administration and systematically evaluated the resulting mucosal and systemic immune responses using ELISpot and ELISAs. All proposed tasks (Table 1) were completed within the twelve-month base period, and the established go/no go metric was successfully achieved. Numerous adjuvant:LcrV:NLP formulations were found to have statistically significant increases in IgA titers in serum and/or lung upon IN administration (compared to IM administration), while also producing robust IgG responses in serum. Some formulations also showed significant IFNγ responses using restimulated splenocytes. The data collected during the base period provide valuable insights for the future design of safe and effective mucosal subunit vaccines while also highlighting areas of research that merit further investigation.