新型疫苗佐剂研究进展

doi:10.16431/j.cnki.1671-7236.2023.06.030

Abstract

Abstract: Adjuvants are immune stimulators that enhance and regulate the immune response of vaccine antigens.They can produce stronger immune response when used together with antigens.Adjuvants can activate the host's innate immune system.When adjuvants and antigens are injected into the body at the same time or in advance, they can change the shape of antigens and prolong their retention in the body, promote the presentation ability of mononuclear phagocytes to antigens and stimulate the proliferation and differentiation of lymphocytes, thereby enhancing the host's immune response to antigens or changing the type of immune response.Adjuvants have a history of more than 100 years.At present, the most widely used vaccine adjuvant is aluminum adjuvant.Traditional inactivated vaccines rely largely on aluminum salt based compounds as the main adjuvant.However, in recent years, with the rapid development of genetic engineering technology and biotechnology, recombinant vaccines, genetic engineering vector vaccines, nucleic acid vaccines and other novel vaccines have been gradually developed.Compared with traditional vaccines, these novel vaccines often have problems such as poor immune response.Due to the early antigen impurity, the traditional aluminum adjuvant can no longer meet the needs.In order to resolve the problem of poor immunogenicity of novel vaccines, researchers are committed to developing novel broad-spectrum and efficient vaccine adjuvants to enhance the efficacy of novel vaccines.Novel vaccine adjuvants have various types, different functions and complex mechanisms.They can be divided into novel oil emulsion adjuvants, liposome adjuvants, CpG oligonucleotide adjuvants, cytokine adjuvants, nano adjuvants, polysaccharide adjuvants and complex system adjuvants.Therefore, the development history, mechanism of action and classification of novel vaccine adjuvants were analyzed and summarized in this review, which would provide reference for the development of novel vaccine adjuvants.

Key words: vaccine adjuvant; novel adjuvant; immunization; nano adjuvant; chiral adjuvant

CLC Number:

S859.79⁺7

HAN Bing, TANG Siqi, ZHU Dawei, LI Hailing, FENG Yali, SU Chaofan, XU Yina, LENG Haoyu, WANG Yongtao, ZHANG Yuemei, TAI Xiaochun, ZHANG Ying. Research Progress of Novel Vaccine Adjuvants[J]. China Animal Husbandry and Veterinary Medicine, 2023, 50(6): 2460-2467.

References

[1] 曾振, 王海宁, 张志芳, 等.新型疫苗佐剂的研究进展[J].生物工程学报, 2021, 37(1):78-87. ZENG Z, WANG H N, ZHANG Z F, et al.Research progress of new vaccine adjuvants[J].Chinese Journal of Biotechnology, 2021, 37(1):78-87.(in Chinese)
[2] HASSETT K J, COUSINS M C, RABIA L, et al.Stabilization of a recombinant ricin toxin A subunit vaccine through lyophilization[J].European Journal of Pharmaceutics and Biopharmaceutics, 2013, 85(2):279-286.
[3] 夏赟, 武梦玉, 张永辉.免疫佐剂的发展现状与未来趋势[J].中国科学基金, 2020, 34(5):573-580. XIA Y, WU M Y, ZHANG Y H.Current status and future trends of immunologic adjuvants[J].Bulletin of National Natural Science Foundation of China, 2020, 34(5):573-580.(in Chinese)
[4] O'HAGAN D T, OTT G S, NEST G V, et al.The history of MF59^® adjuvant:A phoenix that arose from the ashes[J].Expert Review of Vaccines, 2013, 12(1):13-30.
[5] 于永利.AS系列佐剂[J].微生物学免疫学进展, 2017, 45(1):1-6. YU Y L.AS adjuvants[J].Progress in Microbiology and Immunology, 2017, 45(1):1-6.(in Chinese)
[6] XU L, WANG X, WANG W, et al.Enantiomer-dependent immunological response to chiral nanoparticles[J].Nature, 2022, 601(7893):366-373.
[7] BINNEWIES M, MUJAL A M, POLLACK J L, et al.Unleashing type-2 dendritic cells to drive protective antitumor CD4⁺ T cell immunity[J].Cell, 2019, 177(3):556-571.
[8] 李卓凡, 李卫东.MF59佐剂的研究进展[J].国际检验医学杂志, 2016, 37(18):2596-2598. LI Z F, LI W D.Research progress of MF59 adjuvants[J].International Journal of Laboratory Medicine, 2016, 37(18):2596-2598.(in Chinese)
[9] O'HAGAN D T, RAPPUOLI R, DE GREGORIO E, et al.MF59 adjuvant:The best insurance against influenza strain diversity[J].Expert Review of Vaccines, 2011, 10(4):447-462.
[10] 吴晓鑫, 沈吉友, 李方仲, 等.H7N9禽流感病毒裂解佐剂(MF59)疫苗的长期免疫原性研究[J].微生物学免疫学进展, 2019, 47(5):10-15. WU X X, SHEN J Y, LI F Z, et al.Long-term immunogenicity test for avian influenza A H7N9 split vaccine with MF59 adjuvant[J].Progress in Microbiology and Immunology, 2019, 47(5):10-15.(in Chinese)
[11] DOMNICH A, ARATA L, AMICIZIA D, et al.Effectiveness of MF59-adjuvanted seasonal influenza vaccine in the elderly:A systematic review and meta-analysis[J].Vaccine, 2017, 35(4):513-520.
[12] LANSBURY L E, SMITH S, BEYER W, et al.Effectiveness of 2009 pandemic influenza A(H1N1) vaccines:A systematic review and meta-analysis[J].Vaccine, 2017, 35(16):1996-2006.
[13] ZHANG N, JI Q, LIU Z, et al.Effect of different adjuvants on immune responses elicited by protein-based subunit vaccines against SARS-CoV-2 and its delta variant[J].Viruses, 2022, 14(3):501.
[14] OTSUKA T, NISHIDA S, SHIBAHARA T, et al.CpG ODN (K3)-toll-like receptor 9 agonist-induces Th1-type immune response and enhances cytotoxic activity in advanced lung cancer patients:A phase Ⅰstudy[J].BMC Cancer, 2022, 22(1):744.
[15] 陆晨阳, 张婷, 任超超, 等.添加CpG ODN佐剂对鸭坦布苏弱毒活疫苗免疫效果影响研究[J].中国动物传染病学报, 2022, 30(4):54-60. LU C Y, ZHANG T, REN C C, et al.Evaluation of adjuvant effect of CpG ODN on Duck Tembusu virus live attenuated vaccine[J].Chinese Journal of Animal Infectious Diseases, 2022, 30(4):54-60.(in Chinese)
[16] 王长丽, 黄祯雄, 王胜秋, 等.CpG ODN B对鸡新城疫重组杆状病毒疫苗的免疫增强效应[J].生物技术通讯, 2020, 31(4):409-415. WANG C L, HUANG Z X, WANG S Q, et al.Immune enhancement of CpG ODN B on recombinant Baculovirus vaccine against Newcastle disease in chickens[J].Letters in Biotechnology, 2020, 31(4):409-415.(in Chinese)
[17] 闫江泓, 于鹏程, 陶晓燕, 等.CpG寡聚脱氧核苷酸佐剂对狂犬病疫苗免疫效果的影响[J].中国生物制品学杂志, 2017, 30(6):566-570. YAN J H, YU P C, TAO X Y, et al.Influence of CpG oligodeoxynucleotide adjuvant on immune effect of rabies vaccine[J].Chinese Journal of Biologicals, 2017, 30(6):566-570.(in Chinese)
[18] OUYANG K, HIREMATH J, BINJAWADAGI B, et al.Comparative analysis of routes of immunization of a live Porcine reproductive and respiratory syndrome virus (PRRSV) vaccine in a heterologous virus challenge study[J].Veterinary Research, 2016, 47(1):45.
[19] LU W, CUI C, WANG Y, et al.CpG ODN as an adjuvant arouses the vigor of B cells by relieving the negative regulation of surface TLR9 to enhance the antibody response to vaccine[J].Applied Microbiology and Biotechnology, 2021, 105(10):4213-4224.
[20] COOPER C, MACKIE D.Hepatitis B surface antigen-1018 ISS adjuvant-containing vaccine:A review of HEPLISAV^TM safety and efficacy[J].Expert Review of Vaccines, 2011, 10(4):417-427.
[21] HALPERIN S A, MCNEIL S, LANGLEY J M, et al.Safety and immunogenicity of different two-dose regimens of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in healthy young adults[J].Vaccine, 2012, 30(36):5445-5448.
[22] LIN S Y, YAO B Y, HU C J, et al.Induction of robust immune responses by CpG-ODN-loaded hollow polymeric nanoparticles for antiviral and vaccine applications in chickens[J].International Journal of Nanomedicine, 2020, 11(15):3303-3318.
[23] 徐莉, 李敏.CpG ODN佐剂的研究进展及其药学研究的思考[J].中国生物制品学杂志, 2021, 34(12):1524-1528. XU L, LI M.Research progress of CpG ODN adjuvants and thoughts on pharmaceutical research[J].Chinese Journal of Biologicals, 2021, 34(12):1524-1528.(in Chinese)
[24] KHAYYATI K M, DELIREZH N, AGHEBATI M L.CpG-Containing oligodeoxynucleotides and Freund adjuvant in combination with alum augment the production of monoclonal antibodies against recombinant HBsAg[J].Avicenna Journal of Medical Biotechnology, 2022, 14(2):125-131.
[25] JARCZAK D, NIERHAUS A.Cytokine storm-definition, causes, and implications[J].International Journal of Molecular Sciences, 2022, 23(19):11740.
[26] 吴正锋, 彭钰君, 柏银兰.疫苗佐剂的研究进展[J].微生物学免疫学进展, 2022, 50(5):72-77. WU Z F, PENG Y J, BAI Y L.Advances of adjuvants for vaccines[J].Progress in Microbiology and Immunology, 2022, 50(5):72-77.(in Chinese)
[27] DECKER W K, SAFDAR A.Cytokine adjuvants for vaccine therapy of neoplastic and infectious disease[J].Cytokine and Growth Factor Reviews, 2011, 22(4):177-187.
[28] 那君, 胡婧雯, 杨小茜, 等.细胞因子作为人类疫苗佐剂的研究进展[J].现代免疫学, 2016, 36(4):337-340. NA J, HU J W, YANG X Q, et al.Research progress of cytokines as adjuvants of human vaccines[J].Current Immunology, 2016, 36(4):337-340.(in Chinese)
[29] 匡露寒, 季国荣, 杨灿灿, 等. 基于抗原蛋白Fiber-2及细胞因子佐剂的Ⅰ群4型禽腺病毒亚单位疫苗的开发[J]. 中国兽医科学, 2020, 50(4):452-458. KUANG L H, JI G R, YANG C C, et al. Development of group Ⅰ serotype 4 Fowl adenovirus subunit vaccine based on antigen protein Fiber-2 and cytokine adjuvants[J]. Chinese Veterinary Science, 2020, 50(4):452-458. (in Chinese)
[30] MOHAN T, ZHU W, WANG Y, et al.Applications of chemokines as adjuvants for vaccine immunotherapy[J].Immunobiology, 2018, 223(6-7):477-485.
[31] REZAEI F, KESHVARI H, SHOKRGOZAR M A, et al.Nano-adjuvant based on silk fibroin for the delivery of recombinant hepatitis B surface antigen[J].Biomaterials Science, 2021, 9(7):2679-2695.
[32] XU Y, TANG H, LIU J H, et al.Evaluation of the adjuvant effect of silver nanoparticles both in vitro and in vivo[J].Toxicology Letters, 2013, 219(1):42-48.
[33] ASGARY V, SHOARI A, BAGHBANI-ARANI F, et al.Green synthesis and evaluation of silver nanoparticles as adjuvant in rabies veterinary vaccine[J].International Journal of Nanomedicine, 2016, 11:3597-3605.
[34] RAO K, AZIZ S, ROOME T, et al.Gum acacia stabilized silver nanoparticles based nano-cargo for enhanced anti-arthritic potentials of hesperidin in adjuvant induced arthritic rats[J].Artificial Cells, Nanomedicine, and Biotechnology, 2018, 46(sup1):597-607.
[35] LIU H, XIE Z, ZHENG M.Unprecedented chiral nanovaccines for significantly enhanced cancer immunotherapy[J].ACS Applied Materials & Interfaces, 2022, 14(35):39858-39865.
[36] 曲广波, 江桂斌.手性纳米材料的免疫佐剂效应[J].化学进展, 2022, 34(2):239-240. QU G B, JIANG G B.Immune adjuvant effect of chiral nanomaterials[J].Progress in Chemistry, 2022, 34(2):239-240.(in Chinese)
[37] SUN B, YU S, ZHAO D, et al.Polysaccharides as vaccine adjuvants[J].Vaccine, 2018, 36(35):5226-5234.
[38] DMOUR I, ISLAM N.Recent advances on chitosan as an adjuvant for vaccine delivery[J].International Journal of Biological Macromolecules, 2022, 200:498-519.
[39] ACEVEDO K Y, RENU S, SHANMUGASUNDARAM R, et al.Salmonella chitosan nanoparticle vaccine administration is protective against Salmonella Enteritidis in broiler birds[J].PLoS One, 2021, 16(11):e0259334.
[40] 鲁振国.中药多糖提取方法及其免疫增强效果的初步研究[D].广州:华南农业大学, 2019. LU Z G.Extraction method of Chinese traditional medicine polysaccharide and initial study on its immune enhancement effect[D].Guangzhou:South China Agricultural University, 2019.(in Chinese)
[41] 李慧, 宋杰, 董少忠.复合免疫佐剂在疫苗开发中的应用研究进展[J].国际免疫学杂志, 2020, 2:201-208. LI H, SONG J, DONG S Z.Research progress in the application of compound immune adjuvants in vaccine development[J].International Journal of Immunology, 2020, 2:201-208.(in Chinese)
[42] DIDIERLAURENT A M, LAUPEZE B, DI PASQUALE A, et al.Adjuvant system AS01:Helping to overcome the challenges of modern vaccines[J].Expert Review of Vaccines, 2017, 16(1):55-63.
[43] TAKASHIMA E, TACHIBANNA M, MORITA M, et al.Identification of novel malaria transmission-blocking vaccine candidates[J]. Frontiers in Cellular and Infection Microbiology, 2021, 30(11):805-482.
[44] SCARIA P V, ROWE C G, CHEN B B, et al.Protein-protein conjugation enhances the immunogenicity of SARS-CoV-2 receptor-binding domain (RBD) vaccines[J].iScience, 2022, 25(8):104739.
[45] 林海祥, 俞永新.皮卡佐剂和皮卡狂犬病疫苗的安全性[J].中国生物制品学杂志, 2010, 23(1):98-100. LIN H X, YU Y X.Safeties of PICKCa as an adjuvant and rabies vaccine using the adjuvant[J].Chinese Journal of Biologicals, 2010, 23(1):98-100.(in Chinese)
[46] 王树声.一种新型的皮卡(PIKA)佐剂狂犬病疫苗-抢救生命的治疗性疫苗[J].应用预防医学, 2010, 16(1):1-4. WANG S S.A new rabies vaccine with PIKA adjuvant-A life saving therapeutic vaccine[J].Applied Preventive Medicine, 2010, 16(1):1-4.(in Chinese)

Research Progress of Novel Vaccine Adjuvants

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	TAN Shumin, ZHOU Jizhang. Research Progress on Vaccine Immunization and Treatment of Animal Chlamydiosis [J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(5): 1539-1546.
[2]	XIANG Meng, ZHANG Huanrong, REN Yupeng, ZHANG Keke. Sequencing and Genetic Variation Analysis of the Whole Gene of Epidemic Strain of PEDV in Pengzhou,Sichuan Province [J]. China Animal Husbandry and Veterinary Medicine, 2020, 47(1): 209-220.
[3]	WANG Cuicui, ZHOU Shiying, SHI Hao, JIANG Zhiyao, WANG Jianlin. Study on the Effect of Nasal Drip Immunization on the Trachea Function of SPF Chicken [J]. China Animal Husbandry and Veterinary Medicine, 2019, 46(12): 3733-3739.
[4]	XUAN Xiongzhi, LI Wenjia, LI Shaoyu, WEI Fengxian, XU Bin, LIU Jingen. Advances in the Application of Algae in Pig and Chicken Production [J]. China Animal Husbandry and Veterinary Medicine, 2019, 46(11): 3262-3269.
[5]	CHEN Kaiyun, WEN Zhaohai, ZHAI Shaohua, ZHOU Haiying, HU Yuan, JIAN Zijian. Preliminary Study on Immune Effect of Rabies Virus Vaccine Strain with Gene Rearrangement [J]. , 2019, 46(1): 279-286.
[6]	CHANG Jiang-yan, LI Zhao, FEI Shao-jiang, YANG Jian-fa, ZOU Feng-cai. Application of Nanotechnology in Parasitology [J]. , 2017, 44(11): 3294-3299.
[7]	HUANG Yuan, CHEN Jing, ZHAO Cui-ling, CHEN Jin-liang, XIANG Rong, WANG Xiao-hu, XIANG Hua, HUANG Zhong. Identification of Pseudorabies Virus Variant and Control of Pseudorabies [J]. , 2016, 43(9): 2461-2467.
[8]	ZHANG Ling-ling, YUE Yao-jing, FENG Rui-lin, LI Hong-feng, GUO Ting-ting, YUAN Chao, NIU Chun-e, LIU Jian-bin, SUN Xiao-ping, HAN Ji-long, LIU Shan-bo, YANG Bo-hui. Establishment and Optimization of INH Epitope Peptide Vaccine for Detection of Antibody [J]. , 2016, 43(8): 2156-2163.
[9]	LIU Zhao, CHEN Li-gong, WU Xian-jun, LIU Jia, GUO Li. Effect of Radix rehmanniae Extract on Immune Organ Indexes and H9 Vaccine Immune Efficacy of Chicks [J]. , 2016, 43(7): 1780-1784.
[10]	WANG Chao-qun, FANG Xu, SONG Zi-yu, HUANG Yan, PANG Jie, ZHAO Jian-guo. Study on the Change Rule of Egg Yolk Antibody in Laying Hens after First Immunization by Japanese Encephalitis Virus [J]. , 2016, 43(10): 2786-2791.
[11]	WANG Zhen-hua, CAO Xiao-han, SONG He, WANG Di, ZENG Xian-yin. The Harm and Immunization Strategy of Porcine Reproductive and Respiratory Syndrome Virus [J]. , 2014, 41(2): 239-244.
[12]	YANG Liang，XIONG Ben-hai，LV Jian-qiang. Development and Application of Intelligent Awaking System of Immunization and Disinfection in a Scale-size Pig Farm [J]. , 2014, 41(1): 217-221.
[13]	LIU Xia, DU Wei-hua, ZHU Hua-bin, CAO Wen-guang. The Advance of Gene Gun-mediated Gene Delivery in Animals [J]. , 2013, 40(8): 127-133.
[14]	XU Li-ping, SHI Zhen-dan. Study on Effects of Immunization against Growth Hormone Receptor Extracellular Domain on Chicken Growth Performances [J]. , 2013, 40(12): 132-136.
[15]	LIN Qi-ping, CHEN Rui-ai, HUANG Wen-ke, YAN Jie-zhen. Immunization Program of Newcastle Disease, Infectious Bronchitis and Avian Influenza(H9 Subtype)Vaccine, Inactivated (Strain La Sota +Strain M41 +Strain SS/94) [J]. , 2012, 39(6): 192-196.