Impact of plasmid supercoiling on the efficacy of a rabies DNA vaccine to protect cats.
As of today, most DNA vaccination trials have been performed with plasmid preparations highly enriched in supercoiled molecules (sc) and the importance of supercoiled versus open circular (oc) plasmid isoforms for vaccine immunogenicity has only received limited attention. This study demonstrated that a single rabies DNA vaccination fully protected cats against a lethal rabies challenge as early as 3 weeks post vaccination provided that the proportion of supercoiled isoform in the vaccinal solution is at least 48%. In contrast, vaccination with a plasmid containing only 20% of supercoiled molecules induced significant but only partial protection. Further, a single rabies DNA vaccination with plasmids containing at least 70% of supercoiled molecules triggered statistically significant specific antibody titers and specific Th-1 oriented cell-based immunity as early as 2 and 3 weeks post vaccination, respectively. It is concluded that the oc isoforms are less efficient than supercoiled isoforms at inducing a complete profile of immune responses. Therefore, it is proposed that the target threshold of supercoiling that must be met by a rabies DNA vaccine to guarantee optimal immune responses and protection, be set at 70% of supercoiled molecules in the vaccine solution.
Cupillard
Lionel
L
Merial S.A.S., Analytical Biodevelopment, 254 rue Marcel Mérieux, 69007 Lyon, France.
Juillard
Véronique
V
Latour
Sophie
S
Colombet
Guy
G
Cachet
N
N
Richard
S
S
Blanchard
S
S
Fischer
Laurent
L
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D002415:Cats; D004278:DNA, Superhelical / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D007115:Immunization Schedule; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000235:genetics*; D011818:Rabies / Q000517:prevention & control* / Q000821:virology; D011819:Rabies Vaccines / Q000235:genetics* / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D004278:DNA, Superhelical; D004279:DNA, Viral; D011819:Rabies Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma