雾化疫苗研究进展

doi:10.16431/j.cnki.1671-7236.2024.03.032

Abstract

Abstract: In recent years,with the continuous development of mucosal vaccine and immunization technology,the reports of atomized vaccine and corresponding vaccination technology have gradually increased.Atomized vaccine is a kind of vaccine that makes liquid and solid immunogen into droplets (spray immunization) or aerosol particles (aerosol immunization) through atomizing device,and enters human and animal respiratory tract to induce the protective response.Atomized vaccine can induce mucosal immune response better,and at the same time,avoid the risk of disease transmission and pain caused by injection.Since the 1950s,the research on the spray immunization of Newcastle disease vaccine in chickens has opened the prelude of animal respiratory immunity.After that,the spray vaccination of infectious bronchitis vaccine was carried out.At present,the spray immunization of many poultry vaccines has been widely used.The research on aerosol immunization of swine vaccine started late and was more difficult.Since the end of 1970s,the corresponding aerosol immunization research has been carried out on classical swine fever vaccine,Actinobacillus pleuropneumoniae vaccine and Mycoplasma hyopneumoniae vaccine.Compared with animal vaccines,there are more reports on aerosol immunization of human vaccines,mainly focusing on measles vaccine,tuberculosis vaccine and influenza vaccine.Since 2019,the aerosol immunization of COVID-19 vaccine has developed rapidly,and it has been approved for emergency use in China.In this paper,the research status of atomized vaccines for animal and human is systematically stated,and the physical and chemical parameters,safety,tendency in vivo,local immune response in lung and protection effect of various atomized vaccines were summarized,and the future research on vaccine dosage forms,components,atomization generation devices,quality control,immunization program and effect evaluation were put forward.This review could provide a reference for the further research on respiratory mucosal vaccines.

Key words: atomized vaccine; aerosol; herd immunity; prevention and control of infectious diseases

CLC Number:

S859.79⁺7

WU Wei, HAO Fei, XIE Xing, FENG Zhixin. Research Progress on Atomized Vaccines[J]. China Animal Husbandry & Veterinary Medicine, 2024, 51(3): 1203-1213.

References

[1] 冯志新.疫苗气溶胶免疫技术研究进展[J].中国兽药杂志, 2021, 55(6):53-60. FENG Z X.Research progress of aerosol vaccination technology[J].Chinese Journal of Veterinary Drug, 2021, 55(6):53-60.(in Chinese)
[2] SUDDUTH E R, TRAUTMANN-RODRIGUEZ M, GILL N, et al.Aerosol pulmonary immune engineering[J].Advanced Drug Delivery Reviews, 2023, 199:114831.
[3] GOUGH R E, ALEXANDER D J.The speed of resistance to challenge induced in chickens vaccinated by different routes with a b1 strain of live NDV[J].The Veterinary Record, 1973, 92(21):563-564.
[4] GOUGH R E, ALLAN W H.The potential as an aerosol vaccine of ulster 2c strain, Newcastle disease virus[J].The Veterinary Record, 1974, 95(12):263-265.
[5] KIM S J, SPRADBROW P B.Administration of a vaccine prepared from the australian v4 strain of Newcastle disease virus by aerosol and drinking water[J].Australian Veterinary Journal, 1978, 54(10):486-489.
[6] SCHALKOORT R, SPRADBROW P B.Aerosol vaccination of chickens with the v4 strain of Newcastle disease virus[J].Australian Veterinary Journal, 1980, 56(9):429-433.
[7] MEBRAHTU K, TESHALE S, ESATU W, et al.Evaluation of spray and oral delivery of Newcastle disease i2 vaccine in chicken reared by smallholder farmers in Central Ethiopia[J].BMC Veterinary Research, 2018, 14(1):48.
[8] 李清艳,翟向和,史书军,等.气雾免疫在养禽生产中的应用[J].养禽与禽病防治, 2006, 7:37-38. LI Q Y, ZHAI X H, SHI S J, et al.Application of aerosol immunization in poultry production[J].Poultry Husbandry and Disease Control, 2006, 7:37-38.(in Chinese)
[9] 李济清.鸡新城疫Ⅰ系苗气雾免疫效果好[J].湖南畜牧兽医, 1997, 5:21. LI J Q.The aerosol immunization effect of Newcastle disease Ⅰ vaccine is good[J].Hunan Journal of Animal Science&Veterinary Medicine, 1997, 5:21.(in Chinese)
[10] 魏建平,郭鑫,杨汉春.不同免疫途径对肉鸡新城疫气管粘膜抗体的影响[J].中国禽业导刊, 2004, 16:20-21. WEI J P, GUO X, YANG H C.Effects of different immune routes on tracheal mucosal antibodies against Newcastle disease in broilers[J].Guide to Chinese Poultry, 2004, 16:20-21.(in Chinese)
[11] CORBANIE E A, REMON J P, VAN REETH K, et al.Spray drying of an attenuated live Newcastle disease vaccine virus intended for respiratory mass vaccination of poultry[J].Vaccine, 2007, 25(49):8306-8317.
[12] CORIA M F.Protective effect of an inactivated Avian coronavirus vaccine administered by aerosol[J].Archiv Fur Die Gesamte Virusforschung, 1973, 41(1):66-70.
[13] DEUTER A, SOUTHEE D J, MOCKETT A P.Fowlpox virus:Pathogenicity and vaccination of day-old chickens via the aerosol route[J].Research in Veterinary Science, 1991, 50(3):362-364.
[14] BAGHERI S, MITRA T, PAUDEL S, et al.Aerosol vaccination of chicken pullets with irradiated avian pathogenic Escherichia coli induces a local immunostimulatory effect[J].Frontiers in Immunology, 2023, 14:1185232.
[15] GAVRILOV N, PETKOV P, MERMERSKI K.Use of lapinized "C" vaccine as aerosol in immunoprophylaxis against swine fever[J].Archiv Fur Experimentelle Veterinarmedizin, 1980, 34(1):73-78.
[16] 崔显义.猪瘟气雾免疫研究概况[J].兽医导刊, 1983, 2:36-41. CUI X Y.General situation of aerosol immunization of classical swine fever[J].Veterinary Orientation, 1983, 2:36-41.(in Chinese)
[17] 沈阳市科学技术局.气雾免疫法预防猪瘟[J].新农业, 1976, 8:29. SHENYANG BUREAU OF SCIENCE AND TECHNOLOGY.Prevention of classical swine fever by aerosol immunization[J].Modern Agriculture, 1976, 8:29.(in Chinese)
[18] 沈阳市于洪区畜牧兽医站,辽宁大学生物系,沈阳市蔬菜农场.猪瘟气雾免疫[J].新农业, 1978, 19:27-28. SHENYANG YUHONG DISTRICT ANIMAL HUSBANDRY AND VETERINARY STATION, DEPARTMENT OF BIOLOGY, LIAONING UNIVERSITY, SHENYANG VEGETABLE FARM.Aerosol immunization of classical swine fever[J].Modern Agriculture, 1978, 19:27-28.(in Chinese)
[19] 辽宁省兽医卫生站.猪瘟兔化弱毒细胞苗与猪瘟兔化弱毒疫苗气雾免疫试验报告[J].辽宁畜牧兽医, 1980, 2:4-6. LIAONING PROVINCIAL VETERINARY HEALTH STATION.Experimental report on aerosol immunization of attenuated cell vaccine of classical swine fever and attenuated vaccine of classical swine fever[J].Liaoning Journal of Animal Husbandry and Veterinary Medicine, 1980, 2:4-6.(in Chinese)
[20] 郭全胜,刘深庭,于春叶,等.猪瘟气雾免疫实验研究[J].畜禽业, 2004, 6:39. GUO Q S, LIU S T, YU C Y, et al.Experimental study on aerosol immunity of classical swine fever[J].Livestock and Poultry Industry, 2004, 6:39.(in Chinese)
[21] KATINGER A, LUBITZ W, SZOSTAK M P, et al.Pigs aerogenously immunized with genetically inactivated (ghosts) or irradiated Actinobacillus pleuropneumoniae are protected against a homologous aerosol challenge despite differing in pulmonary cellular and antibody responses[J].Journal of Biotechnology, 1999, 73(2-3):251-260.
[22] MURPHY D, VAN ALSTINE W G, CLARK L K, et al.Aerosol vaccination of pigs against Mycoplasma hyopneumoniae infection[J].American Journal of Veterinary Research, 1993, 54(11):1874-1880.
[23] FENG Z X, WEI Y N, LI G L, et al.Development and validation of an attenuated Mycoplasma hyopneumoniae aerosol vaccine[J].Veterinary Microbiology, 2013, 167(3-4):417-424.
[24] HAO F, BAI Y, XIE X, et al.Phenotypic characteristics and protective efficacy of an attenuated Mycoplasma hyopneumoniae vaccine by aerosol administration[J].Vaccine, 2022, 40(42):6074-6083.
[25] 牛青青.猪肺炎支原体超声雾化活疫苗的发生与初步鉴定[D].太谷:山西农业大学, 2016. NIU Q Q.Development and identification of an attenuated Mycoplasma hyopneumoniae aerosol vaccine produced by the ultrasonic method[D].Taigu:Shanxi Agricultural University, 2016.(in Chinese)
[26] 郑鹏.猪支原体肺炎活疫苗rm48株气雾免疫技术的研究[D].泰安:山东农业大学, 2016. ZHENG P.Research on live vaccine RM48 of MPS using by aerosol immunization technique[D].Tai'an:Shandong Agricultural University, 2016.(in Chinese)
[27] 郝飞,白昀,袁厅,等.猪支原体肺炎活疫苗与灭活疫苗联合免疫效果评价[J].中国动物传染病学报, 2023, 31(4):88-94. HAO F, BAI Y, YUAN T, et al.Evaluation of the prime-boost strategy with attenuated vaccine and inactivated vaccine against Mycoplasma hyopneumoniae[J].Chinese Journal of Animal Infectious Diseases, 2023, 31(4):88-94.(in Chinese)
[28] ZHAI L N, ZHAO Y, SONG X L, et al.Inhalable vaccine of bacterial culture supernatant extract mediates protection against fatal pulmonary anthrax[J].Emerging Microbes&Infections, 2023, 12(1):2191741.
[29] GAN C, LUO W, YU Y, et al.Intratracheal inoculation of ahc vaccine induces protection against aerosolized botulinum neurotoxin a challenge in mice[J].NPJ Vaccines, 2021, 6(1):87.
[30] SONG X, ZHANG W, ZHAI L, et al.Aerosolized intratracheal inoculation of recombinant protective antigen (rPA) vaccine provides protection against inhalational anthrax in B10.D2-Hc⁰ mice[J].Frontiers in Immunology, 2022, 13:819089.
[31] 祁文光,胡平,陈友信,等.四种疫(菌)苗对牦牛联合气雾免疫的研究--1.口蹄疫弱毒IB-RS2猪肾传代细胞疫苗对牦牛气雾免疫试验[J].青海畜牧兽医杂志, 1982, 4:39-45. QI W G, HU P, CHEN Y X, et al.Study on the combined aerosol immunity of four kinds of epidemic (bacterial) vaccines to yak--1.Aerosol immunity test of attenuated foot-and-mouth disease IB-RS2 porcine kidney cell vaccine to yak[J].Chinese Qinghai Journal of Animal and Veterinary Sciences, 1982, 4:39-45.(in Chinese)
[32] MANN D D, BUENING G M, THORNE J G.Efficacy of aerosol, intranasal and intramuscular vaccination against selected bovine viral diseases[J].The Cornell Veterinarian, 1983, 73(4):375-379.
[33] MAINA T W, GREGO E A, BOGGIATTO P M, et al.Applications of nanovaccines for disease prevention in cattle[J].Frontiers in Bioengineering and Biotechnology, 2020, 8:608050.
[34] BASSEL L L, CO C, MACDONALD A, et al.Pulmonary and systemic responses to aerosolized lysate of Staphylococcus aureus and Escherichia coli in calves[J].BMC Veterinary Research, 2020, 16(1):168.
[35] SABIN A B.Immunization against measles by aerosol[J].Reviews of Infectious Diseases, 1983, 5(3):514-523.
[36] CUTTS F T, CLEMENTS C J, BENNETT J V.Alternative routes of measles immunization:A review[J].Biologicals, 1997, 25(3):323-338.
[37] DÍAZ-ORTEGA J L, BENNETT J V, CASTAÑEDA-DESALES D, et al.Booster immune response in children 6-7 years of age, randomly assigned to four groups with two mmr vaccines applied by aerosol or by injection[J].Vaccine, 2014, 32(29):3680-3686.
[38] DILRAJ A, CUTTS F T, DE CASTRO J F, et al.Response to different measles vaccine strains given by aerosol and subcutaneous routes to schoolchildren:A randomised trial[J].Lancet(London, England), 2000, 355(9206):798-803.
[39] DILRAJ A, SUKHOO R, CUTTS F T, et al.Aerosol and subcutaneous measles vaccine:Measles antibody responses 6 years after re-vaccination[J].Vaccine, 2007, 25(21):4170-4174.
[40] GRIFFIN D E.Current progress in pulmonary delivery of measles vaccine[J].Expert Review of Vaccines, 2014, 13(6):751-759.
[41] HIREMATH G S, OMER S B.A meta-analysis of studies comparing the respiratory route with the subcutaneous route of measles vaccine administration[J].Human Vaccines, 2005, 1(1):30-36.
[42] LOW N, KRAEMER S, SCHNEIDER M, et al.Immunogenicity and safety of aerosolized measles vaccine:Systematic review and Meta-analysis[J].Vaccine, 2008, 26(3):383-398.
[43] OMER S B, HIREMATH G S, HALSEY N A.Respiratory administration of measles vaccine[J].Lancet(London, England), 2010, 375(9716):706-708.
[44] WONG-CHEW R M, GARCÍA-LEÓN M L, ESPINOSA-TORRES TORRIJA B, et al.Increasing the time of exposure to aerosol measles vaccine elicits an immune response equivalent to that seen in 9-month-old mexican children given the same dose subcutaneously[J].The Journal of Infectious Diseases, 2011, 204(3):426-432.
[45] DE SWART R L, DE VRIES R D, RENNICK L J, et al.Needle-free delivery of measles virus vaccine to the lower respiratory tract of non-human primates elicits optimal immunity and protection[J].NPJ Vaccines, 2017, 2:22.
[46] LICALSI C, CHRISTENSEN T, BENNETT J V, et al.Dry powder inhalation as a potential delivery method for vaccines[J].Vaccine, 1999, 17(13-14):1796-1803.
[47] LICALSI C, MANIACI M J, CHRISTENSEN T, et al.A powder formulation of measles vaccine for aerosol delivery[J].Vaccine, 2001, 19(17-19):2629-2636.
[48] COHEN B J, PARRY R P, ANDREWS N, et al.Laboratory methods for assessing vaccine potency retained in aerosol outputs from nebulizers:Application to world health organization measles aerosol project[J].Vaccine, 2008, 26(27-28):3534-3539.
[49] REYNARD O, GONZALEZ C, DUMONT C, et al.Nebulized fusion inhibitory peptide protects cynomolgus macaques from Measles virus infection[J].Nature Communications, 2022, 13(1):6439.
[50] AGARKHEDKAR S, KULKARNI P S, WINSTON S, et al.Safety and immunogenicity of dry powder measles vaccine administered by inhalation:A randomized controlled phase Ⅰ clinical trial[J].Vaccine, 2014, 32(50):6791-6797.
[51] EDMONDSON W P JR, ROTHENBERG R, WHITE P W, et al.A comparison of subcutaneous, nasal, and combined influenza vaccination.Ⅱ.Protection against natural challenge[J].American Journal of Epidemiology, 1971, 93(6):480-486.
[52] GRUBER W C, HINSON H P, HOLLAND K L, et al.Comparative trial of large-particle aerosol and nose drop administration of live attenuated influenza vaccines[J].The Journal of Infectious Diseases, 1993, 168(5):1282-1285.
[53] VATZIA E, ALLEN E R, MANJEGOWDA T, et al.Respiratory and intramuscular immunization with ChAdOx2-NPM1-NA induces distinct immune responses in H1N1 pdm09 pre-exposed pigs[J].Frontiers in Immunology, 2021, 12:763912.
[54] MARTINI V, PAUDYAL B, CHRUN T, et al.Simultaneous aerosol and intramuscular immunization with influenza vaccine induces powerful protective local T cell and systemic antibody immune responses in pigs[J].Journal of Immunology(Baltimore, Md:1950), 2021, 206(3):652-663.
[55] MORGAN S B, HEMMINK J D, PORTER E, et al.Aerosol delivery of a candidate universal influenza vaccine reduces viral load in pigs challenged with pandemic H1N1 virus[J].Journal of Immunology(Baltimore, Md:1950), 2016, 196(12):5014-5023.
[56] JEMSKI J V, WALKER J S.Aerosol vaccination of mice with a live, temperature-sensitive recombinant Influenza virus[J].Infection and Immunity, 1976, 13(3):818-824.
[57] SMITH J H, BROOKS P, JOHNSON S, et al.Aerosol vaccination induces robust protective immunity to homologous and heterologous influenza infection in mice[J].Vaccine, 2011, 29(14):2568-2575.
[58] SONG K, BOLTON D L, WEI C J, et al.Genetic immunization in the lung induces potent local and systemic immune responses[J].Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(51):22213-22218.
[59] ROSENTHAL S R, MCENERY J T, RAISYS N.Aerogenic BCG vaccination against tuberculosis in animal and human subjects[J].The Journal of Asthma Research, 1968, 5(4):309-323.
[60] MANJALY THOMAS Z R, SATTI I, MARSHALL J L, et al.Alternate aerosol and systemic immunisation with a recombinant viral vector for tuberculosis, MVA85A:A phase Ⅰ randomised controlled trial[J].PLoS Medicine, 2019, 16(4):e1002790.
[61] MANJALY THOMAS Z R, MCSHANE H.Aerosol immunisation for TB:Matching route of vaccination to route of infection[J].Transactions of the Royal Society of Tropical Medicine and Hygiene, 2015, 109(3):175-181.
[62] BARCLAY W R, BUSEY W M, DALGARD D W, et al.Protection of monkeys against airborne tuberculosis by aerosol vaccination with Bacillus calmette-guerin[J].The American Review of Respiratory Disease, 1973, 107(3):351-358.
[63] NUERMBERGER E L, YOSHIMATSU T, TYAGI S, et al.Paucibacillary tuberculosis in mice after prior aerosol immunization with Mycobacterium bovis BCG[J].Infection and Immunity, 2004, 72(2):1065-1071.
[64] WHITE A D, SIBLEY L, DENNIS M J, et al.Evaluation of the safety and immunogenicity of a candidate tuberculosis vaccine, MVA85A, delivered by aerosol to the lungs of macaques[J].Clinical and Vaccine Immunology, 2013, 20(5):663-672.
[65] SATTI I, MEYER J, HARRIS S A, et al.Safety and immunogenicity of a candidate tuberculosis vaccine MVA85A delivered by aerosol in BCG-vaccinated healthy adults:A phase 1, double-blind, randomised controlled trial[J].The Lancet Infectious Diseases, 2014, 14(10):939-946.
[66] HOKEY D A, WACHHOLDER R, DARRAH P A, et al.A nonhuman primate toxicology and immunogenicity study evaluating aerosol delivery of AERAS-402/AD35 vaccine:Evidence for transient T cell responses in peripheral blood and robust sustained responses in the lungs[J].Human Vaccines&Immunotherapeutics, 2014, 10(8):2199-2210.
[67] JEYANATHAN M, FRITZ D K, AFKHAMI S, et al.Aerosol delivery, but not intramuscular injection, of Adenovirus-vectored tuberculosis vaccine induces respiratory-mucosal immunity in humans[J].JCI Insight, 2022, 7(3):e155655.
[68] GAUTAM U S, ASRICAN R, SEMPOWSKI G D.Targeted dose delivery of Mycobacterium tuberculosis in mice using silicon antifoaming agent via aerosol exposure system[J].PLoS One, 2022, 17(10):e0276130.
[69] WHITE A D, SIBLEY L, SARFAS C, et al.Influence of aerosol delivered BCG vaccination on immunological and disease parameters following SARS-CoV-2 challenge in Rhesus macaques[J].Frontiers in Immunology, 2021, 12:801799.
[70] DAVIES B, PRIER J E, JONES C M, et al.Cutting edge:Tissue-resident memory T cells generated by multiple immunizations or localized deposition provide enhanced immunity[J].Journal of Immunology(Baltimore, Md:1950), 2017, 198(6):2233-2237.
[71] SHIN H, IWASAKI A.A vaccine strategy that protects against genital herpes by establishing local memory T cells[J].Nature, 2012, 491(7424):463-467.
[72] XU F, WU S, YI L, et al.Safety, mucosal and systemic immunopotency of an aerosolized Adenovirus-vectored vaccine against SARS-CoV-2 in rhesus macaques[J].Emerging Microbes & Infections, 2022, 11(1):438-441.
[73] WU S, HUANG J, ZHANG Z, et al.Safety, tolerability, and immunogenicity of an aerosolised Adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCOV) in adults:Preliminary report of an open-label and randomised phase 1 clinical trial[J].The Lancet Infectious Diseases, 2021, 21(12):1654-1664.
[74] ZHONG J, LIU S, CUI T, et al.Heterologous booster with inhaled Adenovirus vector COVID-19 vaccine generated more neutralizing antibodies against different SARS-CoV-2 variants[J].Emerging Microbes&Infections, 2022, 11(1):2689-2697.
[75] WANG F Z, ZHANG C H, TANG L, et al.An observational prospective cohort study of vaccine effectiveness against SARS-CoV-2 infection of an aerosolized, inhaled Adenovirus-type-5-vectored COVID-19 vaccine given as a second booster dose in Guangzhou city, China[J].The Journal of Infectious Diseases, 2023.Doi:10.1093/infdis/jiad338.
[76] WANG F, HUANG B, DENG Y, et al.Neutralizing antibody levels associated with injectable and aerosolized Ad5-nCOV boosters and BA.2 infection[J].BMC Medicine, 2023, 21(1):233.
[77] ROH E H, FROMEN C A, SULLIVAN M O.Inhalable mRNA vaccines for respiratory diseases:A roadmap[J].Current Opinion in Biotechnology, 2022, 74:104-109.
[78] CORBETT M, BOGERS W M, HEENEY J L, et al.Aerosol immunization with NYVAC and MVA vectored vaccines is safe, simple, and immunogenic[J].Proceedings of the National Academy of Sciences of the United States of America, 2008, 105(6):2046-2051.

Research Progress on Atomized Vaccines

PDF (PC)

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 5

Recommended Articles

Metrics

Comments

[1]	HOU Xiaohong, WANG Meng, WU Bo, LONG Xianrong, ZHAO Xiaomin, GAO Jing, DAI Peiqiang, CHAI Tongjie. Infectivity of H9N2 Subtype Avian Influenza Virus SD18 Strain and Comparison of the Effects of Different Routes of Infection [J]. China Animal Husbandry & Veterinary Medicine, 2022, 49(4): 1449-1460.
[2]	LI Zhiguo, YU Huan, ZHANG Xinze, DU Yeye, ZHANG Hongmin, CAO Qiqi, GUO Yao, QIAO Tingting, HUO Nairui, LIU Xingguo, GU Shaopeng. Concentration Variation and Aerodynamic Characteristics of Airborne Fungi in Sheep Houses in Southeastern Shanxi Province [J]. China Animal Husbandry & Veterinary Medicine, 2018, 45(7): 2034-2040.
[3]	LEI Cheng-hong, LUO Qiu-jiang, CHEN Yong, LI Wei-dong, CHENG Zhi-ze. Effect of Aerosol OT and Paraformaldehyde Supplement on the Voluntary Intake, Digestion and Metabolism of Late-pregnant Ewe Fed with Ground Diet [J]. China Animal Husbandry & Veterinary Medicine, 2016, 43(1): 121-127.
[4]	ZHANG Xiao-dan, GAO Li-li, HU Jia-qing, AI Wen-hao, CHAI Tong-jie. Study on Aerotransmission of Escherichia coli Carrying the Plasmid-mediated Quinolone Resistance Genes of Swine [J]. China Animal Husbandry & Veterinary Medicine, 2015, 42(7): 1842-1850.
[5]	LI Hao, LUO Qiu-jiang, PAN Rong, ZHOU Feng-wen, Nijiati·keyimu. The Effect of Supplement of Aerosol OT on the Digestion and Absorption in the Former Stomach and Small Intestine of Small-tail Han Sheep Fed with Concentrate-type Diet [J]. China Animal Husbandry & Veterinary Medicine, 2015, 42(11): 2961-2968.