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评估重组糖蛋白基 Chandipura 疫苗与市售 DPT 疫苗联合使用的免疫原性。

Evaluation of the immunogenicity of a recombinant glycoprotein-based Chandipura vaccine in combination with commercially available DPT vaccine.

机构信息

Hepatitis Division, National Institute of Virology, Microbiological Containment Complex, Sus Road, Pashan, Pune 411021, India.

出版信息

Vaccine. 2010 Feb 10;28(6):1463-7. doi: 10.1016/j.vaccine.2009.11.072. Epub 2009 Dec 14.

DOI:10.1016/j.vaccine.2009.11.072
PMID:20005854
Abstract

Chandipura virus (CHPV) belongs to family Rhabdovoridae and has emerged as an encephalitis causing pathogen with high mortality among pediatric population from three Indian states. The recombinant glycoprotein (rGp) was shown to be an excellent vaccine candidate as evaluated in a murine model. As the disease is predominantly rural, to ensure maximum coverage for Chandipura vaccine, an attempt was made to evaluate combination of rGp and a commercially available DPT vaccine (CHP-DPT). When CHP-DPT was used for immunization of mice, 90% seroconversion against rGp with high antibody titers (1:1200 by ELISA and 1:320 by neutralization test) was observed and did not differ from mice immunized with rGp alone (P>0.05). Similarly seroconversions and antibody titers against DPT were comparable in mice immunized with DPT alone or in combination with rGp. Seroconversions and antibody titers ranged from 90 to 100% and 1:1200 to 1:2400 respectively. Intracerebral challenge with homologous CHPV strain resulted in 90% survival in rGp alone and CHP-DPT groups. Lymphocyte proliferative responses were also comparable. Thus, neither components of the candidate combination vaccine inhibited immune response to the other component. Substantial decrease of CHPV RNA and absence of histopathological changes in the brains of surviving immunized mice after challenge than the unimmunized controls further confirm efficacy of the vaccine even after intracerebral challenge. In conclusion, a combination vaccine seems feasible for use in a restricted area where the disease is endemic and should be subjected to additional studies required for future use in humans.

摘要

钱德普拉病毒(CHPV)属于 Rhabdovoridae 科,已成为导致印度三个邦儿科人群死亡率高的脑炎病原体。在小鼠模型中评估表明,重组糖蛋白(rGp)是一种出色的疫苗候选物。由于该疾病主要发生在农村地区,为确保 Chandipura 疫苗的最大覆盖率,尝试评估 rGp 与市售 DPT 疫苗(CHP-DPT)的联合使用。当使用 CHP-DPT 对小鼠进行免疫接种时,观察到 90%的 rGp 血清转化率,抗体滴度高(ELISA 为 1:1200,中和试验为 1:320),与单独使用 rGp 免疫的小鼠无差异(P>0.05)。同样,单独或与 rGp 联合免疫的小鼠对 DPT 的血清转化率和抗体滴度也相似。血清转化率和抗体滴度分别为 90%至 100%和 1:1200 至 1:2400。用同源 CHPV 株进行脑内攻毒后,rGp 单独和 CHP-DPT 组的存活率均为 90%。淋巴细胞增殖反应也相当。因此,候选联合疫苗的成分均未抑制对另一种成分的免疫反应。与未免疫对照相比,攻毒后存活免疫小鼠的脑中 CHPV RNA 大量减少且没有组织病理学变化进一步证实了疫苗的功效,即使在脑内攻毒后也是如此。总之,对于疾病流行的有限地区,联合疫苗似乎是可行的,应该进行更多研究,以用于未来的人类使用。

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