Efficacy, immunogenicity and stability of a novel intranasal Nanoemulsion-adjuvanted influenza vaccine in a murine model

Abstract

Mutations of influenza virus increase concerns of worldwide epidemics resulting from the newly emergent strains. Current influenza vaccines are inefficient and require annual vaccinations. W805EC adjuvant is an oil-in-water emulsion composed of nanodroplets with an average diameter of approximately 400 nm. The nanoemulsion adjuvant has been used successfully to stimulate the immune response when mixed with several other antigens in animal models. In this study, W805EC nanoemulsion adjuvant activity was evaluated using nasal influenza vaccination in a murine model. Five to twenty percent W805EC adjuvant was used to inactivate influenza A/Puerto Rico/8/34/05 (H1N1). Mice immunized with the nanoemulsion adjuvanted influenza virus intranasally showed a robust specific humoral immune response as demonstrated using ELISA and HAI assays. Serum HAI titers were more than 104 following two vaccinations. Vaccinated mice were also protected against challenge with an LD80 of live influenza virus. Splenocytes from vaccinated mice were assayed for cytokine production following virus stimulation. The cytokine profile demonstrated a robust cellular immune response with enhanced Th1 and Th17 immunity that provided balanced immunity against both intracellular and extracellular forms of the virus. Additionally, the vaccine preparations showed minimal protein degradation but remained potent when stored at 4°C for up to three months. This work demonstrates that W805EC nanoemulsion adjuvant can effectively enhance the immunogenicity of influenza hemagglutinin antigen. The nanoemulsion adjuvant can result in antigen sparing and cross-protection. The potential exists for a nasally administered influenza vaccine that may require little or no refrigerated storage.

Intranasal Immunization of Ferrets with Commercial Trivalent Influenza Vaccines Formulated in a Nanoemulsion-Based Adjuvant

“…W 80 5EC adjuvant was either used to inactivate live A/Puerto Rico/8/34 (H1N1) influenza virus or mixed with ␤-propiolactone-inactivated virus (20). W 80 5EC-adjuvanted vaccine induced a Th17 response that was present in addition to a significantly enhanced Th1 bias (20).…”

“…W 80 5EC adjuvant was either used to inactivate live A/Puerto Rico/8/34 (H1N1) influenza virus or mixed with ␤-propiolactone-inactivated virus (20). W 80 5EC-adjuvanted vaccine induced a Th17 response that was present in addition to a significantly enhanced Th1 bias (20). In other studies, when an NE adjuvant prototype was combined with purified antigens such as recombinant anthrax protective antigen (8) and HIV gp120, it elicited a Th1 systemic response with neutralizing serum antibodies and mucosal IgA when it was administered intranasally to mice or guinea pigs (9).…”

“…These data suggest broad adjuvant activity and an acceptable safety profile for the W 80 5EC adjuvant. NE adjuvant activity resulting in mucosal, systemic, and Th1 and Th17 cellular immunity and in protection against challenge was also seen in mice immunized with influenza virus inactivated with ␤-propiolactone (20).…”

Intranasal nanoemulsion-based inactivated respiratory syncytial virus vaccines protect against viral challenge in cotton rats

“…26 NE adjuvants have been shown to generate robust, protective immune responses in mice and other rodents for a variety of different pathogens, including anthrax, influenza, hepatitis B, vaccinia and RSV. [23][24][25][26][27][28][29][30][31][32][33][34][35] Live RSV is inactivated directly by the NE. The resulting inactivated virus retains the native antigen structure, unlike chemical inactivation which can alter the structure of epitopes critical for mounting an immune response appropriate for the virus.…”

Construction and Immunological Evaluation of Immunostimulatory Nanocomposites with Vaccine Potential

“…Hamouda et al [29,30] developed an influenza vaccine adjuvant oil-in-water nanoemulsion-based adjuvant W805EC, which immunized ferrets or mice by nasal cavity to produce safe and specific cellular and humoral immune responses. The hemagglutination inhibitory antibody produced by the nanoemulsionbased adjuvant vaccine was 19 to 90 times that of without the adjuvant vaccine.…”