Abstract:
Delayed release of vaccine coupled with a soluble vaccine acts as a primer and a booster with only a single administration, which would be very beneficial to livestock producers. We developed a subdermal pellet consisting of solid-phase pure stearic acid (SA) or palmitic acid (PA) that was used to encapsulate a small volume liquid vaccine consisting of fluorescently labeled *Ovalbumin (Cy5-*OVA) formulated with Emulsigen-D +/- Poly I:C (EMP) adjuvants. Mice were also immunized via the subcutaneous route with Cy5-*OVA-EMP (soluble liquid). The vaccine leached out of the pellet with very little dissolution of the fat itself resulting in the sustained subdermal delivery of antigens and adjuvants. Cy5-*OVA was still visible 60 days post administration in mice immunized with stearic acid-coated or palmitic acid-coated pellets. In these mice, persistently high IgG1 and IgG2a antibody titres were detected as well as significant IFNγ production at least 60 days post-injection. These responses were significantly higher than those observed after a single subcutaneous injection of the vaccine. A repeat trial with the pellets alone +/- the soluble vaccine showed comparable immune responses after surgical implantation of the pellet, suggesting that pellet alone may be sufficient. The PA-coated vaccines led to dermal inflammation in the mice that would limit usefulness of this vehicle, but this was largely absent when SA was used to coat the pellets. These data suggest that the SA-coated adjuvanted vaccine prolonged the release of the vaccine and triggered a comparable immune response to the mice that received the two liquid injections, and a single pellet vaccine should be tested as a novel immunization method for livestock.
摘要:
与可溶性疫苗结合的疫苗的延迟释放仅在单次给药时充当引物和加强剂。这对畜牧业生产者非常有利。我们开发了一种由固相纯硬脂酸(SA)或棕榈酸(PA)组成的皮下颗粒,用于包封小体积的液体疫苗,该疫苗由荧光标记的*卵清蛋白(Cy5-OVA)与乳化剂-D/-聚I:C(EMP)佐剂配制。还通过皮下途径用Cy5-*OVA-EMP(可溶性液体)免疫小鼠。疫苗从颗粒中浸出,脂肪本身很少溶解,导致抗原和佐剂的持续皮下递送。Cy5-*OVA在施用后60天在用硬脂酸包被或棕榈酸包被的小丸免疫的小鼠中仍然可见。在这些老鼠身上,在注射后至少60天检测到持续高的IgG1和IgG2a抗体滴度以及显著的IFNγ产生。这些应答显著高于单次皮下注射疫苗后观察到的应答。单独使用颗粒的重复试验+/-可溶性疫苗在手术植入颗粒后显示出相当的免疫反应,表明单独的颗粒可能就足够了。PA包被的疫苗导致小鼠皮肤炎症,这将限制这种载体的有用性,但是当SA用于包覆颗粒时,这在很大程度上是不存在的。这些数据表明,SA包被的佐剂疫苗延长了疫苗的释放,并引发了与接受两次液体注射的小鼠相当的免疫反应。单颗粒疫苗应作为一种新的牲畜免疫方法进行测试。