Pre-Clinical Immunogenicity and Protective Efficacy of a Recombinant Subunit West Nile Virus Vaccine Formulated with Aluminum Hydroxide Adjuvant.

West Nile Virus (WNV) is endemic throughout the world and is a leading cause of mosquito-borne severe and/or fatal encephalitic disease. Although several promising WNV vaccines have been developed, none have been approved for human use. Studies were conducted to evaluate the immunogenicity, protective efficacy, and safety of a recombinant subunit WNV candidate vaccine (WN-80E) formulated with aluminum hydroxide (Alhydrogel™) adjuvant and/or in combination with a semi-synthetic saponin (GPI-0100) adjuvant in mice and hamsters, and for toxicology, immunogenicity and safety in rabbits. Adult mice and hamsters were immunized twice via the intramuscular (IM) route 3 to 4 weeks apart with escalating doses of WN-80E adsorbed to Alhydrogel™. Mice were also immunized with WN-80E in combination with the GPI-0100 adjuvant. All animals were subsequently challenged with a lethal dose of virulent WNV. The rabbits received four IM immunizations 3 weeks apart with WN-80E/Alhydrogel™ that was compared to WN-80E/Alhydrogel™ plus various amounts of GPI-0100. The results of immunogenicity and challenge experiments demonstrated that all WN-80E vaccine formulations with Alhydrogel™ with or without GPI-0100 were immunogenic and afforded complete protection to mice and hamsters against morbidity and mortality following challenge with WNV. Also, the WN-80E/Alhydrogel formulations with or without GPI-0100 were well tolerated and elicited high neutralizing antibody (nAb) titers in rabbits. Cumulatively, because these findings demonstrated that the WN-80E formulated with Alhydrogel™ alone elicited robust antibody responses and protection against viral challenge, this formulation was selected for further evaluation in clinical trials for the prevention of WNV disease in humans.