Lee Eun Young, Lee Sena, Rho Semi, Kim Jae-Ouk, Choi Seuk Keun, Lee Young Jin, Park Joo Young, Song Manki, Yang Jae Seung
Clinical Research Laboratory, Sciences Unit, International Vaccine Institute, Seoul, Korea.
EuBiologics Co. Ltd., Chuncheon, Korea.
Clin Exp Vaccine Res. 2018 Jul;7(2):104-110. doi: 10.7774/cevr.2018.7.2.104. Epub 2018 Jul 31.
An oral cholera vaccine (OCV), Euvichol, with thimerosal (TM) as preservative, was prequalified by the World Health Organization (WHO) in 2015. In recent years, public health services and regulatory bodies recommended to eliminate TM in vaccines due to theoretical safety concerns. In this study, we examined whether TM-free Euvichol induces comparable immunogenicity to its TM-containing formulation in animal model.
To evaluate and compare the immunogenicity of the two variations of OCV, mice were immunized with TM-free or TM-containing Euvichol twice at 2-week interval by intranasal or oral route. One week after the last immunization, mice were challenged with O1 and daily monitored to examine the protective immunity against cholera infection. In addition, serum samples were obtained from mice to measure vibriocidal activity and vaccine-specific IgG, IgM, and IgA antibodies using vibriocidal assay and enzyme-linked immunosorbent assay, respectively.
No significant difference in immunogenicity, including vibriocidal activity and vaccine-specific IgG, IgM, and IgA in serum, was observed between mice groups administered with TM-free and -containing Euvichol, regardless of immunization route. However, intranasally immunized mice elicited higher levels of serum antibodies than those immunized via oral route. Moreover, intranasal immunization completely protected mice against challenge but not oral immunization. There was no significant difference in protection between two Euvichol variations.
These results suggested that TM-free Euvichol could provide comparable immunogenicity to the WHO prequalified Euvichol containing TM as it was later confirmed in a clinical study. The pulmonary mouse cholera model can be considered useful to examine the potency of OCVs.
一种以硫柳汞（TM）作为防腐剂的口服霍乱疫苗Euvichol于2015年获得世界卫生组织（WHO）的预认证。近年来，由于理论上的安全担忧，公共卫生服务机构和监管机构建议在疫苗中去除TM。在本研究中，我们在动物模型中检测了不含TM的Euvichol是否能诱导出与其含TM制剂相当的免疫原性。
为了评估和比较两种口服霍乱疫苗的免疫原性，小鼠通过鼻内或口服途径，每隔2周用不含TM或含TM的Euvichol免疫两次。最后一次免疫后1周，用O1对小鼠进行攻毒，并每天监测以检测对霍乱感染的保护性免疫。此外，从小鼠采集血清样本，分别使用杀弧菌试验和酶联免疫吸附试验测量血清中的杀弧菌活性以及疫苗特异性IgG、IgM和IgA抗体。
无论免疫途径如何，给予不含TM和含TM的Euvichol的小鼠组之间，在免疫原性方面均未观察到显著差异，包括血清中的杀弧菌活性以及疫苗特异性IgG、IgM和IgA。然而，鼻内免疫的小鼠产生的血清抗体水平高于口服免疫的小鼠。此外，鼻内免疫能完全保护小鼠免受攻毒，但口服免疫则不能。两种Euvichol变体在保护作用上没有显著差异。
这些结果表明，不含TM的Euvichol能产生与WHO预认证的含TM的Euvichol相当的免疫原性，这一点随后在一项临床研究中得到了证实。肺部小鼠霍乱模型可被认为有助于检测口服霍乱疫苗的效力。
