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Recombinant Ov-ASP-1, a Th1-Biased Protein Adjuvant Derived from the Helminth Onchocerca volvulus, Can Directly Bind and Activate Antigen-Presenting Cells

Yuxian He^1,2,*,, Sophie J. Barker^1,,, Angus J. MacDonald^1,3,*,, Yu Yu^*, Long Cao^*, Jingjing Li^*, Ranjit Parhar^*, Susanne Heck^*, Susanne Hartmann^¶, Douglas T. Golenbock^||, Shibo Jiang^*, Nathan A. Libri, Amanda E. Semper, William M. Rosenberg^,# and Sara Lustigman^*

^* Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065; Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Beijing, China; iQur, Southampton General Hospital, Southampton, U.K.; Liver Group, Division of IIR Southampton University, Southampton General Hospital, Southampton, U.K.; ^¶ Molecular Parasitology, Humboldt University, Germany; ^|| Department of Medicine, Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, MA 01655.; and ^# Center for Hepatology, University College London, London, U.K.

We previously reported that rOv-ASP-1, a recombinant Onchocerca volvulus activation associated protein-1, was a potent adjuvant for recombinant protein or synthetic peptide-based Ags. In this study, we further evaluated the adjuvanticity of rOv-ASP-1 and explored its mechanism of action. Consistently, recombinant full-length spike protein of SARS-CoV or its receptor-binding domain in the presence of rOv-ASP-1 could effectively induce a mixed but Th1-skewed immune response in immunized mice. It appears that rOv-ASP-1 primarily bound to the APCs among human PBMCs and triggered Th1-biased proinflammatory cytokine production probably via the activation of monocyte-derived dendritic cells and the TLR, TLR2, and TLR4, thus suggesting that rOv-ASP-1 is a novel potent innate adjuvant.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Y.H., S.J.B., and A.J.MacD. contributed equally to this work.

² Address correspondence and reprint requests to Dr. Yuxian He, Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th Street, New York, NY 10065. E-mail address: yhe{at}nybloodcenter.org

³ Current address: Wyeth Research, Aberdeen, Scotland.

⁴ Abbreviations used in this paper: PAMP, pathogen associated molecular pattern; ASP, activation-associated secreted protein; Ov-ASP-1, Onchocerca volvulus activation associated protein-1; SARS-CoV, severe acute respiratory syndrome coronavirus; S, spike protein; RBD, receptor-binding domain; DC, dendritic cell; MoDC, monocyte-derived DC; CBA, cytometric bead array; CAT, chloramphenicol acetyl transferase; NHD, normal healthy donor; wt, wild type; CHO, Chinese hamster ovary; HEK, human embryonic kidney cell; MPL, monophosphoryl lipid A; TDM, trehalose dicorynomycolate; HCV, hepatitis C virus.