| 160 | 0 | 50 |
| 下载次数 | 被引频次 | 阅读次数 |
在前期研究中，我们构建了表达HIV-1 AEgp145的多种载体疫苗，包括质粒p VR、5型35型嵌合型腺病毒载体（Ad5F35）及修饰的痘苗病毒安卡拉株载体（MVA），在小鼠体内单独免疫两次或多种疫苗联合均显示良好的免疫原性。本研究主要探讨上述疫苗单独及与表达HIV-1 gag基因的Ad5-HIVgag疫苗联合单次免疫的效果。首先对上述疫苗进行了验证，三种疫苗分别单次免疫小鼠，另设Ad5F35-AEgp145及r MVA-AEgp145分别与Ad5-HIVgag同时免疫。结果显示，免疫后2周各疫苗组AEgp145特异性细胞免疫反应均达峰值，以Ad5F35-AEgp145组及Ad5F35-AEgp145联合Ad5-HIVgag组最强，显著高于其他组，在免疫后24周仍维持较高水平。这两个实验组在免疫后2周HIV-1 gp120特异性结合抗体可被检出，之后一直维持在较高的水平；并于4～16周检测到AE亚型中和抗体，其他疫苗组抗体水平较低或检测不出。以上结果提示，Ad5F35-AEgp145单独或与Ad5-HIVgag联合单次免疫能在小鼠体内诱导强而持久的特异性细胞和体液免疫应答。
Abstract：In previous studies, a series of vector vaccines expressing HIV-1 AEgp145 were constructed,including the plasmid pVR, a chimeric adenovirus type 5 vector containing the fiber protein of adenovirus type35(Ad5F35), and a recombinant modified vaccinia virus Ankara vector(rMVA). These vaccinesdemonstrated high immunogenicity in mice following either two administrations alone or combined immunizationwith multiple vaccines. In this study, we evaluated the immunogenicity of a single-dose immunization using eachvaccine individually or in combination with the Ad5-HIVgag vaccine. First, the expression of the target antigenby each vaccine was confirmed. Subsequently, mice were immunized with a single dose of each vaccine alone orco-immunized with Ad5F35-AEgp145 or rMVA-AEgp145 together with Ad5-HIVgag. Two weeks post-immunization, AEgp145-specific cellular immune responses peaked in all vaccine groups, with the strongestresponses observed in the Ad5F35-AEgp145 group and the Ad5F35-AEgp145 combined with Ad5-HIVgaggroup, both significantly higher than those in other groups. These elevated cellular responses were sustained upto 24 weeks post-vaccination. HIV-1 gp120-specific binding antibodies were detectable in both Ad5F35 groupsfrom 2 weeks post-immunization and remained at high levels thereafter. Anti-AE subtype neutralizing antibodieswere detected between 4 and 16 weeks post-immunization, whereas antibody levels in other vaccine groupswere low or undetectable. These findings suggest that a single dose of Ad5F35-AEgp145, either alone orcombined with Ad5-HIVgag, can induce robust and durable HIV-1-specific cellular and humoral immuneresponses in mice.
[1] Chen CW, Saubi N, Joseph-MunnéJ. Design concepts of virus-like particle-based HIV-1 vaccines[J]. Front Immunol, 2020, 11:573157. DOI:10. 3389/fimmu. 2020. 573157.
[2] Volberding PA, Deeks SG. Antiretroviral therapy and management of HIV infection[J]. Lancet, 2010, 376(9734):49-62. DOI:10. 1016/S0140-6736(10)60676-9.
[3] Excler JL, Robb ML, Kim JH. HIV-1 vaccines:challenges and new perspectives[J]. Hum Vaccin Immunother, 2014, 10(6):1734-1746. DOI:10. 4161/hv. 28462.
[4] Kwong PD, Mascola JR. HIV-1 vaccines based on antibody identification, B cell ontogeny, and epitope structure[J]. Immunity, 2018, 48(5):855-871. DOI:10. 1016/j. immuni. 2018. 04. 029.
[5] Hao J, Zheng S, Gan M, et al. Changing proportions of HIV-1 subtypes and transmitted drug resistance among newly diagnosed HIV/AIDS individuals-China, 2015and 2018[J]. China CDC Wkly, 2021, 3(53):1133-1138. DOI:10. 46234/ccdcw2021. 251.
[6] Arunachalam PS, Charles TP, Joag V, et al. T cellinducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers[J].Nat Med, 2020, 26(6):932-940. DOI:10. 1038/s41591-020-0858-8.
[7] Larijani MS, Ramezani A, Sadat SM. Updated studies on the development of HIV therapeutic vaccine[J]. Curr HIV Res, 2019, 17(2):75-84. DOI:10. 2174/1570162X17666190618160608.
[8] Burton DR. Advancing an HIV vaccine; advancing vaccinology[J]. Nat Rev Immunol, 2019, 19(2):77-78. DOI:10. 1038/s41577-018-0103-6.
[9] Faurez F, Dory D, Le Moigne V, et al. Biosafety of DNA vaccines:New generation of DNA vectors and current knowledge on the fate of plasmids after injection[J]. Vaccine, 2010, 28(23):3888-3895. DOI:10. 1016/j. vaccine. 2010. 03. 040.
[10]Stickl H, Hochstein-Mintzel V, Mayr A, et al. MVAstufenimpfung Gegen pocken[J]. Dtsch Med Wochenschr, 1974, 99(47):2386-2392. DOI:10. 1055/s-0028-1108143.
[11]Stickl HA. Smallpox vaccination and its consequences:first experiences with the highly attenuated smallpox vaccine“MVA”[J]. Prev Med, 1974, 3(1):97-101.DOI:10. 1016/0091-7435(74)90066-8.
[12]Ramírez JC, Gherardi MM, Esteban M. Biology of attenuated modified vaccinia virus Ankara recombinant vector in mice:virus fate and activation of B-and T-cell immune responses in comparison with the Western Reserve strain and advantages as a vaccine[J]. J Virol,2000, 74(2):923-933. DOI:10. 1128/jvi. 74. 2. 923-933. 2000.
[13]陈丹瑛，汪孟冉，何小周，et al. HIV-1中国流行株CRF01_AE env基因改造及其重组DNA疫苗的构建[J].中华实验和临床病毒学杂志，2014, 28(3):227-229 DOI:10. 3760/cma. j. issn. 1003-9279. 2014. 03. 023.
[14]冯霞，余双庆，刘红梅，等. HIV-1 B亚型gag基因密码子优化及其免疫原性的研究[J].病毒学报，2008,24(3):190-195. DOI:10. 3321/j. issn:1000-8721. 2008. 03. 005.
[15]何小周，杨靖，李红霞，等.重组HIV-AEgp145和SIV-envT基因的rAAV8在小鼠体内的免疫原性研究[J].病毒学报，2021, 37(3):613-620. DOI:10. 13242/j.cnki. bingduxuebao. 003971.
[16]余双庆，冯霞，刘红梅，等.重组HIV-1 gp120 AAV2/1在小鼠和恒河猴体内的免疫原性[J].病毒学报，2010, 26(2):115-120. DOI:10. 13242/j. cnki.bingduxuebao. 002066.
[17]刘红梅，余双庆，冯霞，et al. 1型和2型外壳蛋白构建的AAV载体携带HIV-1 gag诱导免疫反应的比较研究[J].病毒学报，2007(03):177-182 DOI.
[18]Crank MC, Wilson EMP, Novik L, et al. Safety and immunogenicity of a rAd35-EnvA prototype HIV-1vaccine in combination with rAd5-EnvA in healthy adults(VRC 012)[J]. PLoS One, 2016, 11(11):e0166393. DOI:10. 1371/journal. pone. 0166393.
[19]Keefer MC, Gilmour J, Hayes P, et al. A phase I double blind, placebo-controlled, randomized study of a multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults[J]. PLoS One, 2012, 7(8):e41936. DOI:10. 1371/journal. pone. 0041936.
[20]Ma Q, Yang J, Zhang X, et al. Immunogenicity of HIV-1 Env mRNA and Env-gag VLP mRNA vaccines in mice[J]. Vaccines(Basel), 2025, 13(1):84. DOI:10. 3390/vaccines13010084.
[21]He X, Chen D, Ma Q, et al. Decade-long sustained cellular immunity induced by sequential and repeated vaccination with four heterologous HIV vaccines in Rhesus macaques[J]. Vaccines, 2025, 13(4):338.DOI:10. 3390/vaccines13040338.
基本信息:
DOI：10.13242/j.cnki.bingduxuebao.250106
中图分类号:R392
引用信息:
[1]郝彦哲,马琦,杨靖,等.基于HIV-1 AEgp145基因的多载体疫苗在小鼠体内单独及与gag基因疫苗联合免疫研究[J].病毒学报,2025,41(03):784-791.DOI:10.13242/j.cnki.bingduxuebao.250106.
基金信息:
艾滋病和病毒性肝炎等重大传染病防治科技重大专项（项目号：2018ZX10731101-002-010）,题目：MVA及Ad5载体疫苗联合应用的临床前研究~~
2025-03-23
2025
2025-04-08
2025-05-06
2025
1
2025-05-08
2025-05-08
2025-05-08