Randomized phase I trial HIV-CORE 003: Depletion of serum amyloid P component and immunogenicity of DNA vaccination against HIV-1

PloS One
Nicola BorthwickMark B Pepys

Abstract

The failure of DNA vaccination in humans, in contrast to its efficacy in some species, is unexplained. Observational and interventional experimental evidence suggests that DNA immunogenicity may be prevented by binding of human serum amyloid P component (SAP). SAP is the single normal DNA binding protein in human plasma. The drug (R)-1-[6-[(R)-2-carboxypyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC, miridesap), developed for treatment of systemic amyloidosis and Alzheimer's disease, depletes circulating SAP by 95-99%. The proof-of-concept HIV-CORE 003 clinical trial tested whether SAP depletion by CPHPC would enhance the immune response in human volunteers to DNA vaccination delivering the HIVconsv immunogen derived from conserved sub-protein regions of HIV-1. Human volunteers received 3 intramuscular immunizations with an experimental DNA vaccine (DDD) expressing HIV-1-derived immunogen HIVconsv, with or without prior depletion of SAP by CPHPC. All subjects were subsequently boosted by simian (chimpanzee) adenovirus (C)- and poxvirus MVA (M)-vectored vaccines delivering the same immunogen. After administration of each vaccine modality, the peak total magnitudes, kinetics, functionality and memory subsets ...Continue Reading

References

Aug 30, 1991·Clinica Chimica Acta; International Journal of Clinical Chemistry·S R NelsonM B Pepys
Oct 14, 1987·Biochemical and Biophysical Research Communications·M B Pepys, P J Butler
Oct 4, 2007·PloS One·Sven LétourneauTomás Hanke
Nov 18, 2008·Lancet·M Juliana McElrathUNKNOWN Step Study Protocol Team
Feb 1, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yue WangShuhan Sun
Oct 30, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Nicola BorthwickTomáš Hanke
Feb 5, 2014·Expert Opinion on Biological Therapy·Tomáš Hanke
Sep 13, 2016·Molecular Therapy. Methods & Clinical Development·Gaudensia MutuaThe Hiv-Core 004 Study Group

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