Soboll G, Nelson K M, Leuthner E S, Clark R J, Drape R, Macklin M D, Swain W F, Olsen C W, Lunn D P
School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive West, Madison, WI 53706, USA.
Vaccine. 2003 Jun 20;21(21-22):3081-92. doi: 10.1016/s0264-410x(03)00161-0.
We have previously demonstrated that equine influenza virus hemagglutinin (HA) DNA vaccination protects ponies from challenge infection, and induces protective IgGa and IgGb responses. However, this approach does not induce a nasal IgA response. The objective of this study was to examine the value of cholera toxin (CT) administration as an adjuvant for intranasal HA DNA vaccination, and to measure protection 3 months after DNA vaccination. After an immunogenic dose of CT was determined, ponies were immunized on two occasions by intranasal administration of HA DNA and cholera toxin, or HA DNA alone. Ponies in both groups received two additional HA DNA particle mediated vaccinations at skin and mucosal sites. Antibody responses, and protection from challenge infection 3 months after the last vaccination were studied and compared to an influenza virus naive control group. Ponies in both vaccination groups produced virus-specific IgG antibodies in serum following vaccination and showed clinical protection from challenge infection 3 months after the last vaccination. Co-administration of CT plus HA DNA vaccination induced a nasal IgA response. In addition, analysis of antibody titers in nasal secretions indicated local production of nasal IgGb, which was amplified by CT administration.
我们之前已经证明,马流感病毒血凝素(HA)DNA疫苗接种可保护小马免受攻毒感染,并诱导产生保护性IgGa和IgGb反应。然而,这种方法不会诱导鼻腔IgA反应。本研究的目的是检验霍乱毒素(CT)作为鼻内HA DNA疫苗接种佐剂的价值,并在DNA疫苗接种3个月后测定其保护效果。在确定免疫原性剂量的CT后,小马分两次通过鼻内接种HA DNA和霍乱毒素或仅接种HA DNA进行免疫。两组小马在皮肤和黏膜部位额外接受两次HA DNA颗粒介导的疫苗接种。研究了最后一次疫苗接种3个月后的抗体反应和对攻毒感染的保护作用,并与未接触流感病毒的对照组进行比较。两个疫苗接种组的小马在接种疫苗后血清中均产生了病毒特异性IgG抗体,并在最后一次疫苗接种3个月后显示出对攻毒感染的临床保护作用。CT与HA DNA疫苗联合接种诱导了鼻腔IgA反应。此外,对鼻分泌物中抗体滴度的分析表明,鼻腔局部产生了IgGb,CT接种可增强其产生。