Immuno‐stimulatory effects of bacterial‐derived plasmids depend on the nature of the antigen in intramuscular DNA inoculations

Abstract

SUMMARYThe CpG motifs of bacterial-derived plasmids augment antigen-specific immune responses and steer those responses towards the T helper 1 ( Th1) type. In this study, we have addressed the immuno-stimulatory effect of intramuscular co-administration of CpG motifs containing vector DNA on the modulation of immune responses to the haemagglutinin (HA) and the nucleoprotein (NP) proteins of influenza virus. The co-administration of vector DNA with a HA-encoding plasmid DNA showed a significant enhancement in the total IgG response, the generation of cytotoxic T lymphocyte (CTL), and the T-cell proliferative response. In the case of NP-encoding plasmid DNA inoculations, the co-administration of vector DNA slightly decreased the total IgG response, although the IgG2a/IgG1 ratio and the CTL responses to NP were significantly increased. These observations suggest that the immuno-stimulatory effects of bacterial-derived plasmids depend upon the nature of the co-administered antigen.

Biodegradable Particles as Vaccine Delivery Systems: Size Matters

“…A higher proportion of IgG2a antibodies relative to IgG1 antibodies correlates with secretion of a set of cytokines that favor CTL proliferation (4). Thus, the IgG2a:IgG1 ratio reflects the phenotype of Ag specific responses generated as a result of vaccination (34). Irrespective of size, all particulated groups demonstrated significantly greater levels (p<0.05) of OVA-specific IgG2a antibodies than soluble OVA plus CpG.…”

“…Higher proportions of IgG2a antibodies relative to IgG1 antibodies correlate with secretion of a set of cytokines that favor CTL proliferation (4). Thus, a higher IgG2a:IgG1 is desirable to generate an Ag specific cellular response as a result of vaccination (34). To estimate levels of these antibodies in peripheral blood, serum samples were collected via submandibular bleeding.…”

Antipeptide Antibody Responses following Intranasal Immunization: Effectiveness of Mucosal Adjuvants

“…Initially, it was reported that these motifs could induce in vitro production of interleukin-6 (IL-6) and gamma interferon (IFN-␥) by CD4 ϩ T cells, IL-6 and IL-12 by B cells, and IFN-␥ by NK cells (20). Such properties led to the use of CpG ODNs as adjuvants in several experimental models (11,21,22,23) and, indeed, studies published thus far support the view that Th1-type responses dominate after CpG coadministration with an immunogen. The nature of the immune response developed depends on the age of the animals (2,21), the route of antigen delivery (2), and the nature of the antigen (22); nevertheless, the potential of CpG motifs as adjuvants for delivery via the mucosal surfaces is particularly promising (3,25,26,27).…”

Induction of Cell-Mediated Immunity againstMycobacterium tuberculosisUsing DNA Vaccines Encoding Cytotoxic and Helper T-Cell Epitopes of the 38-Kilodalton Protein

“…Improvement of the cellular immune response and protection by the coadministration of different plasmids have also been achieved by other researchers. Lee et al (19), for example, observed an increase in antigen-specific CTL induction, T-cell proliferation, and specific antibody secretion after coadministration of a plasmid encoding the hemagglutinin of influenza A virus with the empty vector DNA.…”