Feline Leukemia Virus DNA Vaccine Efficacy Is Enhanced by Coadministration with Interleukin-12 (IL-12) and IL-18 Expression Vectors

The expectation that cell-mediated immunity is important in the control of feline leukemia virus (FeLV) infection led us to test a DNA vaccine administered alone or with cytokines that favored the development of a Th1 immune response. The vaccine consisted of two plasmids, one expressing the gag/pol genes and the other expressing the env gene of FeLV-A/Glasgow-1. The genetic adjuvants were plasmids encoding the feline cytokines interleukin-12 (IL-12), IL-18, or gamma interferon (IFN-γ). Kittens were immunized by three intramuscular inoculations of the FeLV DNA vaccine alone or in combination with plasmids expressing IFN-γ, IL-12, or both IL-12 and IL-18. Control kittens were inoculated with empty plasmid. Following immunization, anti-FeLV antibodies were not detected in any kitten. Three weeks after the final immunization, the kittens were challenged by the intraperitoneal inoculation of FeLV-A/Glasgow-1 and were then monitored for a further 15 weeks for the presence of virus in plasma and, at the end of the trial, for latent virus in bone marrow. The vaccine consisting of FeLV DNA with the IL-12 and IL-18 genes conferred significant immunity, protecting completely against transient and persistent viremia, and in five of six kittens protecting against latent infection. None of the other vaccines provided significant protection.

细胞介导免疫在猫白血病病毒（feline leukemia virus, FeLV）感染防控中发挥关键作用这一认知，促使我们开展了DNA疫苗的相关测试：该疫苗可单独给药，或与可促进Th1型免疫应答发育的细胞因子联合施用。本次测试的DNA疫苗由两种质粒组成：一种表达FeLV-A/Glasgow-1的gag/pol基因，另一种表达其env基因。所用基因佐剂为编码猫源细胞因子的质粒，分别为白细胞介素-12（interleukin-12, IL-12）、IL-18以及γ干扰素（gamma interferon, IFN-γ）。实验幼猫通过三次肌肉注射进行免疫：分别接种单独的FeLV DNA疫苗，或联合表达IFN-γ、IL-12，或同时表达IL-12与IL-18的质粒；空白对照组幼猫则接种空质粒。免疫后，所有幼猫均未检测到抗FeLV抗体。末次免疫三周后，通过腹腔接种FeLV-A/Glasgow-1对幼猫进行攻毒，随后持续监测15周以检测血浆中的病毒载量，并在实验结束时检测骨髓中的潜伏病毒。联合IL-12与IL-18基因的FeLV DNA疫苗可诱导显著免疫保护：可完全抵御一过性及持续性病毒血症，且在6只幼猫中的5只体内实现了潜伏感染的防控；其余各组疫苗均未提供显著保护效果。