In vivo targeting of porcine reproductive and respiratory syndrome virus antigen through porcine DC-SIGN to dendritic cells elicits antigen-specific CD4T cell immunity in pigs

Sakthivel Subramaniam, Pablo Piñeyro, Debin Tian, Christopher Overend, Danielle M. Yugo, Shannon R. Matzinger, Adam J. Rogers, Mary Etna R Haac, Qian Cao, C. Lynn Heffron, Nicholas Catanzaro, Scott P. Kenney, Yao Wei Huang, Tanja Opriessnig, Xiang Jin Meng

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Immunogenicity of protein subunit vaccines may be dramatically improved by targeting them through antibodies specific to c-type lectin receptors (CLRs) of dendritic cells in mice, cattle, and primates. This novel vaccine development approach has not yet been explored in pigs or other species largely due to the lack of key reagents. In this study, we demonstrate that porcine reproductive and respiratory syndrome virus (PRRSV) antigen was targeted efficiently to dendritic cells through antibodies specific to a porcine CLR molecule DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) in pigs. A recombinant PRRSV antigen (shGP45M) was constructed by fusing secretory-competent subunits of GP4, GP5 and M proteins derived from genetically-shuffled strains of PRRSV. In vaccinated pigs, when the PRRSV shGP45M antigen was delivered through a recombinant mouse-porcine chimeric antibody specific to the porcine DC-SIGN (pDC-SIGN) neck domain, porcine dendritic cells rapidly internalized them in vitro and induced higher numbers of antigen-specific interferon-γ producing CD4T cells compared to the pigs receiving non-targeted PRRSV shGP45M antigen. The pDC-SIGN targeting of recombinant antigen subunits may serve as an alternative or complementary strategy to existing vaccines to improve protective immunity against PRRSV by inducing efficient T cell responses.

Original languageEnglish (US)
Pages (from-to)6768-6775
Number of pages8
JournalVaccine
Volume32
Issue number50
DOIs
StatePublished - Nov 28 2014
Externally publishedYes

Keywords

  • DC-SIGN
  • Dendritic cell targeting
  • Porcine reproductive and respiratory syndrome virus (PRRSV)
  • Subunit vaccine
  • T cell immunity

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

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