Genetic co-transfer of CCR7 ligands enhances immunity and prolongs survival against virulent challenge of pseudorabies virus

• Published in: Immunology and cell biology 2009-01, Vol.87 (1), p.91-99
• Main Authors: Han, Young Woo, Aleyas, Abi G, George, Junu A, Kim, Seon Ju, Kim, Hye Kyung, Yoo, Dong Jin, Kang, Seong Ho, Eo, Seong Kug
• Format: Article
• Language: English
• Subjects: Animals; Antibody Formation; CCR7 ligands; Chemokine CCL19 - genetics; Chemokine CCL19 - immunology; Chemokine CCL21 - genetics; Chemokine CCL21 - immunology; Cytokines - biosynthesis; Cytokines - immunology; dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - virology; DNA vaccine; Female; Mice; Mice, Inbred C57BL; Pseudorabies - immunology; Pseudorabies - prevention & control; Pseudorabies Vaccines - administration & dosage; Pseudorabies Vaccines - genetics; Pseudorabies Vaccines - immunology; Pseudorabies virus; Receptors, CCR7 - immunology; Transfection; Vaccines, DNA - administration & dosage; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Viral Envelope Proteins - immunology
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1038/icb.2008.69

The CC chemokine receptor 7 (CCR7) and cognate CCR7 ligands, CCL19 and CCL21, help establish microenvironments in lymphoid tissue that can facilitate encounters between naive T cells and mature dendritic cells (DCs). This study was conducted to determine if CCR7 ligands can augment the immunogenicity of a DNA vaccine that expresses glycoprotein B (gB) of the pseudorabies virus (PrV). The genetic co‐transfer of CCR7 ligands along with a PrV DNA vaccine increased the levels of serum PrV‐specific immunoglobulin (Ig) G by 2‐ to 2.5‐fold. In addition, the level of PrV‐specific IgG2a isotype was significantly enhanced by co‐injection of CCR7 ligand DNA, which indicates that CCR7 ligand biases the humoral immunity toward the Th1‐type pattern. The co‐injection of CCR7 ligand DNA consistently enhanced the level of Th1‐type cytokines (IL‐2 and IFN‐γ) produced by stimulated immune cells when compared with a group that was vaccinated with the PrV DNA vaccine. Also, the genetic co‐transfer of CCR7 ligand DNAs with PrV DNA vaccine provided prolonged survival against a virulent challenge by PrV. Moreover, the co‐administration of CCR7 ligand DNA increased the number of mature DCs into the secondary lymphoid tissues, which appeared to enhance the proliferation of PrV‐immune CD4+ T cells. Taken together, these findings indicate that CCR7 ligands are an attractive adjuvant for a PrV DNA vaccine that can offer protective immunity against the PrV.