Azevedo Marli S P, Gonzalez Ana Maria, Yuan Lijuan, Jeong Kwang-Il, Iosef Cristiana, Van Nguyen Trang, Lovgren-Bengtsson Karin, Morein Bror, Saif Linda J
Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, OH 44691, USA.
Clin Vaccine Immunol. 2010 Mar;17(3):420-8. doi: 10.1128/CVI.00395-09. Epub 2010 Jan 27.
We determined the impact of mucosal prime/boost regimens and vaccine type (attenuated Wa human rotavirus [AttHRV] or nonreplicating Wa 2/6 rotavirus-like particles [VLP]) on protection and antibody-secreting cell (ASC) responses to HRV in a neonatal gnotobiotic pig disease model. Comparisons of delivery routes for AttHRV and evaluation of nonreplicating VLP vaccines are important as alternative vaccine approaches to overcome risks associated with live oral vaccines. Groups of neonatal gnotobiotic pigs were vaccinated using combinations of oral (PO) and intranasal (IN) inoculation routes as follows: (i) 3 oral doses of AttHRV (AttHRV3xPO); (ii) AttHRV3xIN; (iii) AttHRVPO, then 2/6VLP2xIN; (iv) AttHRVIN, then 2/6VLP2xIN; and (v) mock-inoculated controls. Subsets of pigs from each group were challenged with virulent Wa HRV [P1A(8) G1] (4 weeks post-primary inoculation) to assess protection. The AttHRVPO+2/6VLP2xIN pigs had the highest protection rates against virus shedding and diarrhea (71% each); however, these rates did not differ statistically among the vaccine groups, except for the AttHRVIN+2/6VLPIN group, which had a significantly lower protection rate (17%) against diarrhea. The isotype, magnitude, and tissue distribution of ASCs were analyzed by enzyme-linked immunospot assay. The highest mean numbers of virus-specific IgG and IgA ASCs were observed pre- and postchallenge in both intestinal and systemic lymphoid tissues of the AttHRVPO+2/6VLPIN group. Thus, the AttHRVPO+2/6VLPIN vaccine regimen using immunostimulating complexes (ISCOM) and multiple mucosal inductive sites, followed by AttHRV3xPO or IN regimens, were the most effective vaccine regimens, suggesting that either AttHRVPO+2/6VLPIN or AttHRV3xIN may be an alternative approach to AttHRV3xPO for inducing protective immunity against rotavirus diarrhea.
我们在新生无菌仔猪疾病模型中，确定了黏膜初免/加强免疫方案和疫苗类型（减毒活疫苗Wa株人轮状病毒[AttHRV]或非复制型Wa 2/6轮状病毒样颗粒[VLP]）对轮状病毒（HRV）保护作用及抗体分泌细胞（ASC）应答的影响。比较AttHRV的接种途径及评估非复制型VLP疫苗，作为克服与口服活疫苗相关风险的替代疫苗方法具有重要意义。将新生无菌仔猪分为几组，采用口服（PO）和鼻内（IN）接种途径的组合进行疫苗接种，具体如下：（i）3剂口服AttHRV（AttHRV3xPO）；（ii）3剂鼻内AttHRV（AttHRV3xIN）；（iii）先口服AttHRV，然后2剂鼻内接种2/6VLP（AttHRVPO，then 2/6VLP2xIN）；（iv）先鼻内接种AttHRV，然后2剂鼻内接种2/6VLP（AttHRVIN，then 2/6VLP2xIN）；以及（v） mock接种对照。在初次接种后4周，每组选取部分仔猪用强毒株Wa HRV [P1A(8) G1]进行攻毒，以评估疫苗的保护作用。AttHRVPO + 2/6VLP2xIN组仔猪对病毒排泄和腹泻的保护率最高（均为71%）；然而，除AttHRVIN + 2/6VLPIN组对腹泻的保护率显著较低（17%）外，各疫苗组之间的保护率无统计学差异。通过酶联免疫斑点试验分析ASC的亚型、数量及组织分布。在AttHRVPO + 2/6VLPIN组仔猪的肠道和全身淋巴组织中，攻毒前后均观察到病毒特异性IgG和IgA ASC的平均数量最高。因此，采用免疫刺激复合物（ISCOM）和多个黏膜诱导部位的AttHRVPO + 2/6VLPIN疫苗方案，继以AttHRV3xPO或IN方案，是最有效的疫苗方案，这表明AttHRVPO + 2/6VLPIN或AttHRV3xIN可能是替代AttHRV3xPO诱导抗轮状病毒腹泻保护性免疫的一种方法。
