Deck R R, DeWitt C M, Donnelly J J, Liu M A, Ulmer J B
Department of Virus and Cell Biology, Merck Research Laboratories, West Point, PA 19486, USA.
Vaccine. 1997 Jan;15(1):71-8. doi: 10.1016/s0264-410x(96)00101-6.
We have examined in detail the characteristics of the humoral immune response and protective efficacy induced by an influenza hemagglutinin (HA) DNA vaccine. In mice injected intramuscularly with HA DNA, the magnitude of the immune responses generated, as measured by ELISA and hemagglutination inhibiting (HI) antibodies, was directly related to the amount of DNA injected and the number of doses administered. The level of anti-HA antibodies in DNA-vaccinated mice was higher than that in convalescent immune mice and was maintained for at least 1.5 years. The immunoglobulin isotype profile of the antibodies was predominantly IgG2a, similar to that induced by live virus infection but in contrast to the relative abundance of IgG1 antibodies observed after inoculation with formalin-inactivated whole virus. The presence of pre-challenge HI antibodies was found to be a good correlate of protection, in that every animal with a detectable HI titer was protected from a lethal challenge. Complete protection from a lethal dose of influenza virus (A/PR/34), as judged by 100% survival and no weight loss, was conferred by as little as 1 microgram of DNA (given twice). Furthermore, mice injected with 10 to 100 micrograms doses, when subsequently challenged with virus, showed no increase in HI titer and no production of antibodies directed against the challenge virus, suggesting a substantial inhibition of virus replication after challenge.
我们已经详细研究了流感血凝素（HA）DNA疫苗诱导的体液免疫反应特征和保护效力。在肌肉注射HA DNA的小鼠中，通过ELISA和血凝抑制（HI）抗体检测到的免疫反应强度与注射的DNA量和给药剂量直接相关。DNA疫苗接种小鼠中的抗HA抗体水平高于恢复期免疫小鼠，并且至少维持1.5年。抗体的免疫球蛋白亚型谱主要为IgG2a，类似于活病毒感染诱导的情况，但与接种福尔马林灭活全病毒后观察到的IgG1抗体相对丰度相反。发现攻击前HI抗体的存在与保护密切相关，即每个具有可检测HI效价的动物都受到致死性攻击的保护。仅1微克DNA（注射两次）就能提供完全保护，免受致死剂量流感病毒（A/PR/34）的攻击，表现为100%存活且无体重减轻。此外，注射10至100微克剂量的小鼠在随后受到病毒攻击时，HI效价没有增加，也没有产生针对攻击病毒的抗体，这表明攻击后病毒复制受到显著抑制。
