Chikungunya Virus-Like Particle Immunogenicity: Alum as a Dose-Sparing and Stability-Inducing Agent Lo Vang, Carla Uranga, Ben Guenther, Jason Mendy, Danielle Thompson, Elena Betancourt, Amit Jain, Payal Gala, Amish Patel, Paul Shabram, Jon Smith, and Jeff Alexander PaxVax, San Diego, CA 92121, USA
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes an acute febrile disease often associated with prolonged arthritic complications. It is spread by Aedes mosquitos, and has emerged throughout most tropical areas of the world where these vectors are prevalent. Endemic areas of chikungunya virus are expanding due to globalization factors and changing weather patterns that enable further spread of the Aedes vectors. There are currently no licensed vaccines available for chikungunya, although studies in animals indicate that induction of neutralizing antibody appears to be sufficient for protection against infection. A virus-like particle (VLP) vaccine has been developed for chikungunya, and has been tested in phase 1 and phase 2 clinical studies without adjuvant.
Aluminum Hydroxide (alum) has been successfully used in protein-based vaccines to enhance immunogenicity, increase the duration of immune responses, and to promote product stability. We evaluated the VLP binding capacity of alum (Alhydrogel®) and demonstrated that over 85% of CHIKV VLPs were adsorbed in 15 minutes. Electron microscopy, micro BCA, and Gyros assays were used to monitor the adsorption and stability of CHIKV VLP adsorbed to alum. We also evaluated the effect of alum on the immunogenicity of the VLP vaccine by immunization of C57Bl6 x Balb/c mice in dose titration studies with or without adsorption to alum. We demonstrated in these studies that alum provided a significant dose-sparing effect and increased CHIKV-specific neutralizing antibody titers approximately five-fold as compared to non-adjuvanted CHIKV VLPs. The stability of the CHIKV VLPs absorbed to alum was maintained for 12 months at 2-8°C as demonstrated by immunogenicity in mice. These results indicate that alum provides a significant adjuvant effect on the immunogenicity of the CHIK VLP vaccine, and provides a stable product at 2-8C. Based in part on these studies, a Phase 2b clinical trial is ongoing which will evaluate the effects of alum on CHIKV VLP immunogenicity in humans.
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