Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a Krebs cycle intermediate (SDH) in an animal model

Rabies is the most lethal zoonotic, vaccine-preventable viral disease in the world. Its treatment is complicated by insufficient vaccine supply and the requirement for four to five repeated injections, as commercially available inactivated rabies lack adjuvant and have low immunogenicity. In this st...

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Main Authors: Liu Ze, Li Zonglin, Wu Ya’Nan, Song Shaohui, Yang Huijuan, Cai Wei, Weidong Li, Guoyang Liao
Format: Article
Language:English
Published: Taylor & Francis Group 2019-02-01
Series:Human Vaccines & Immunotherapeutics
Subjects:
Online Access:http://dx.doi.org/10.1080/21645515.2018.1531966
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author Liu Ze
Li Zonglin
Wu Ya’Nan
Song Shaohui
Yang Huijuan
Cai Wei
Weidong Li
Guoyang Liao
author_facet Liu Ze
Li Zonglin
Wu Ya’Nan
Song Shaohui
Yang Huijuan
Cai Wei
Weidong Li
Guoyang Liao
author_sort Liu Ze
collection DOAJ
description Rabies is the most lethal zoonotic, vaccine-preventable viral disease in the world. Its treatment is complicated by insufficient vaccine supply and the requirement for four to five repeated injections, as commercially available inactivated rabies lack adjuvant and have low immunogenicity. In this study, we focused on the role of a Krebs cycle intermediate, succinate dehydrogenase (SDH), in the innate immune response to cytokine production. We formulated a novel nanoemulsion adjuvant, Golden03, which stabilizes mouse SDH activity and contains more coenzyme Q10 and succinic acid than the classic MF59 adjuvant. Mice were immunized on days 1, 3, and 7, with seroconversion rate results suggesting that Golden03 significantly enhanced vaccine-stimulated antibody production against the rabies virus. Neutralizing antibody concentration testing by RFFIT indicated that treatment with Golden03 could result in antibody levels of up to 0.74 IU/mL 5 days post infection (DPI). ELISPOT for IFN-γ in mouse spleen cells showed that Golden03 enhanced immune responses at 14 DPI, inducing a rapid and powerful cellular response compared to the control group. Furthermore, the Vaccine-Golden03 group displayed no obvious weight loss or death after intracranial injection with CVS-11. An additional advantage is that Golden03 allowed for a three-quarter reduction in dose, while maintaining its efficacy and rapid stimulation effect. We suggest that Golden03 could be developed as a potential adjuvant for use in human rabies vaccine.
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spelling doaj.art-a55b99f1267c4f09aaa087e2124302bd2023-09-22T08:38:24ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2019-02-0115238839610.1080/21645515.2018.15319661531966Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a Krebs cycle intermediate (SDH) in an animal modelLiu Ze0Li Zonglin1Wu Ya’Nan2Song Shaohui3Yang Huijuan4Cai Wei5Weidong Li6Guoyang Liao7Chinese Academy of Medical Science and Peking Union Medical CollegeChinese Academy of Medical Science and Peking Union Medical CollegeChinese Academy of Medical Science and Peking Union Medical CollegeChinese Academy of Medical Science and Peking Union Medical CollegeChinese Academy of Medical Science and Peking Union Medical CollegeChinese Academy of Medical Science and Peking Union Medical CollegeChinese Academy of Medical Science and Peking Union Medical CollegeChinese Academy of Medical Science and Peking Union Medical CollegeRabies is the most lethal zoonotic, vaccine-preventable viral disease in the world. Its treatment is complicated by insufficient vaccine supply and the requirement for four to five repeated injections, as commercially available inactivated rabies lack adjuvant and have low immunogenicity. In this study, we focused on the role of a Krebs cycle intermediate, succinate dehydrogenase (SDH), in the innate immune response to cytokine production. We formulated a novel nanoemulsion adjuvant, Golden03, which stabilizes mouse SDH activity and contains more coenzyme Q10 and succinic acid than the classic MF59 adjuvant. Mice were immunized on days 1, 3, and 7, with seroconversion rate results suggesting that Golden03 significantly enhanced vaccine-stimulated antibody production against the rabies virus. Neutralizing antibody concentration testing by RFFIT indicated that treatment with Golden03 could result in antibody levels of up to 0.74 IU/mL 5 days post infection (DPI). ELISPOT for IFN-γ in mouse spleen cells showed that Golden03 enhanced immune responses at 14 DPI, inducing a rapid and powerful cellular response compared to the control group. Furthermore, the Vaccine-Golden03 group displayed no obvious weight loss or death after intracranial injection with CVS-11. An additional advantage is that Golden03 allowed for a three-quarter reduction in dose, while maintaining its efficacy and rapid stimulation effect. We suggest that Golden03 could be developed as a potential adjuvant for use in human rabies vaccine.http://dx.doi.org/10.1080/21645515.2018.1531966rabiesadjuvantifn gammasdhactivity
spellingShingle Liu Ze
Li Zonglin
Wu Ya’Nan
Song Shaohui
Yang Huijuan
Cai Wei
Weidong Li
Guoyang Liao
Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a Krebs cycle intermediate (SDH) in an animal model
Human Vaccines & Immunotherapeutics
rabies
adjuvant
ifn gamma
sdh
activity
title Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a Krebs cycle intermediate (SDH) in an animal model
title_full Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a Krebs cycle intermediate (SDH) in an animal model
title_fullStr Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a Krebs cycle intermediate (SDH) in an animal model
title_full_unstemmed Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a Krebs cycle intermediate (SDH) in an animal model
title_short Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a Krebs cycle intermediate (SDH) in an animal model
title_sort application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a krebs cycle intermediate sdh in an animal model
topic rabies
adjuvant
ifn gamma
sdh
activity
url http://dx.doi.org/10.1080/21645515.2018.1531966
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