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NPJ Vaccines. 2018 Sep 26;3:39. doi: 10.1038/s41541-018-0077-1. eCollection 2018.

A combination of TLR-4 agonist and saponin adjuvants increases antibody diversity and protective efficacy of a recombinant West Nile Virus antigen.

Author information

1
1Infectious Disease Research Institute, 1616 Eastlake Ave E., Suite 400, Seattle, WA 98102 USA.
2
2Pathobiology Program, Department of Global Health, University of Washington, Seattle, WA 98195 USA.
3
Imdaptive Inc., 3010 Northwest 56th Street, Seattle, WA 98107 USA.
4
4Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave, Seattle, WA 98109 USA.
5
5PAI Life Sciences Incorporated, 1616 Eastlake Avenue, Suite 250, Seattle, WA 98102 USA.
6
6Hawaii Biotech Inc., 99-193 Aiea Heights Drive, Aiea, HI 96701 USA.
7
7Leidos Inc., 11951 Freedom Drive, Reston, VA 20190 USA.

Abstract

Members of the Flaviviridae family are the leading causes of mosquito-borne viral disease worldwide. While dengue virus is the most prevalent, the recent Zika virus outbreak in the Americas triggered a WHO public health emergency, and yellow fever and West Nile viruses (WNV) continue to cause regional epidemics. Given the sporadic nature of flaviviral epidemics both temporally and geographically, there is an urgent need for vaccines that can rapidly provide effective immunity. Protection from flaviviral infection is correlated with antibodies to the viral envelope (E) protein, which encodes receptor binding and fusion functions. TLR agonist adjuvants represent a promising tool to enhance the protective capacity of flavivirus vaccines through dose and dosage reduction and broadening of antiviral antibody responses. This study investigates the ability to improve the immunogenicity and protective capacity of a promising clinical-stage WNV recombinant E-protein vaccine (WN-80E) using a novel combination adjuvant, which contains a potent TLR-4 agonist and the saponin QS21 in a liposomal formulation (SLA-LSQ). Here, we show that, in combination with WN-80E, optimized SLA-LSQ is capable of inducing long-lasting immune responses in preclinical models that provide sterilizing protection from WNV challenge, reducing viral titers following WNV challenge to undetectable levels in Syrian hamsters. We have investigated potential mechanisms of action by examining the antibody repertoire generated post-immunization. SLA-LSQ induced a more diverse antibody response to WNV recombinant E-protein antigen than less protective adjuvants. Collectively, these studies identify an adjuvant formulation that enhances the protective capacity of recombinant flavivirus vaccines.

Conflict of interest statement

David E. Clements and Dr. D. Elliot Parks are employees of Hawaii Biotech, a for-profit entity that has provided the antigen used in these studies. Neither had a significant role in the design and execution of the experiments, or in interpretation of the study results. The remaining authors declare no competing interests.

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