{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:45:40Z","timestamp":1767869140378,"version":"3.49.0"},"reference-count":31,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Capacity building-Research","award":["ZDGWNLJS25-35"],"award-info":[{"award-number":["ZDGWNLJS25-35"]}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"crossref","award":["2018ZX10731101-002-010"],"award-info":[{"award-number":["2018ZX10731101-002-010"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: Developing an effective vaccine is crucial for the prevention and control of AIDS. Viral vector-based vaccines, particularly those utilizing homologous or heterologous prime-boost strategies, represent an important direction in current HIV vaccine research. Methods: In this study, replication-defective chimeric adenovirus Ad5F35 and modified vaccinia virus Ankara (rMVA) vector vaccines expressing the HIV-1 AEgp145 were successfully constructed, designated as Ad5F35-AEgp145 and rMVA-AEgp145, respectively. Sixty BALB\/c mice were randomly divided into three groups: Ad5F35 alone, rMVA prime\/Ad5F35 boost, and PBS control. The mice were immunized intramuscularly at weeks 0 and 3, and humoral and cellular immune responses were assessed at 4, 8, 12, and 16 weeks after the initial immunization. Results: The homologous Ad5F35 and heterologous rMVA\/Ad5F35 vaccination regimens elicited comparable levels of HIV Env-specific cellular immune responses, peaking at 2100 \u00b1 222 SFCs\/million splenocytes and 2200 \u00b1 619 SFCs\/million splenocytes, respectively (p &gt; 0.05). Compared to the heterologous regimen, the homologous Ad5F35 regimen induced significantly higher levels of gp120-binding antibodies at weeks 4 and 8 post-initial immunization, with geometric mean titers of 1:25,600 \u00b1 7011 versus 1:1280 \u00b1 150.7 and 1:10,240 \u00b1 4048 versus 1:2560 \u00b1 391.9, respectively. Furthermore, neutralizing activity at week 8 was significantly higher in the homologous group, with a 50% neutralization titers of 1:45 compared to 1:12 in the heterologous group (p &lt; 0.01). Conclusion: This study demonstrates that the Ad5F35-AEgp145 vaccine, whether administered alone or in combination with rMVA-AEgp145, effectively induces strong and comparable cellular immune responses targeting HIV-1 Env in mice. While both regimens are effective, homologous immunization elicits moderately higher levels of antibody responses. These findings provide an important foundation for the further investigation of vector-based HIV vaccine formulations.<\/jats:p>","DOI":"10.3390\/v18010079","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T12:35:47Z","timestamp":1767702947000},"page":"79","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of Immune Responses Elicited by Ad5F35-AEgp145 Alone or in Combination with rMVA-AEgp145"],"prefix":"10.3390","volume":"18","author":[{"given":"Jing","family":"Yang","sequence":"first","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Ma","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9292-5788","authenticated-orcid":false,"given":"Xiaozhou","family":"He","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongxia","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoguang","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0111-9826","authenticated-orcid":false,"given":"Yanzhe","family":"Hao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Feng","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Chen, C.W., Saubi, N., and Joseph-Munn\u00e9, J. (2020). Design Concepts of Virus-Like Particle-Based HIV-1 Vaccines. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.573157"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1093\/infdis\/jiz650","article-title":"Low-Abundance Drug-Resistant HIV-1 Variants in Antiretroviral Drug-Naive Individuals: A Systematic Review of Detection Methods, Prevalence, and Clinical Impact","volume":"221","author":"Mbunkah","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.antiviral.2009.09.015","article-title":"Clinical management of HIV-1 resistance","volume":"85","author":"Paredes","year":"2010","journal-title":"Antivir. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.32607\/20758251-2019-11-1-14-22","article-title":"Consensus Integrase of a New HIV-1 Genetic Variant CRF63_02A1","volume":"11","author":"Agapkina","year":"2019","journal-title":"Acta Naturae"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Guo, S., Luke, B.T., Henry, A.R., Darko, S., Brandt, L.D., Su, L., Sun, D., Wells, D., Joseph, K.W., and Demirov, D. (2022). HIV infected CD4+ T cell clones are more stable than uninfected clones during long-term antiretroviral therapy. PLoS Pathog., 18.","DOI":"10.1371\/journal.ppat.1010726"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1038\/sj.gt.3302590","article-title":"Prime-boost vaccination with plasmid DNA and a chimeric adenovirus type 5 vector with type 35 fiber induces protective immunity against HIV","volume":"12","author":"Xin","year":"2005","journal-title":"Gene Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/415331a","article-title":"Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity","volume":"415","author":"Shiver","year":"2002","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7625","DOI":"10.1128\/JVI.76.15.7625-7631.2002","article-title":"Different patterns of immune responses but similar control of a simian-human immunodeficiency virus 89.6P mucosal challenge by modified vaccinia virus Ankara (MVA) and DNA\/MVA vaccines","volume":"76","author":"Amara","year":"2002","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Perdiguero, B., S\u00e1nchez-Corzo, C., Sorzano, C.O.S., Saiz, L., Mediavilla, P., Esteban, M., and G\u00f3mez, C.E. (2019). A Novel MVA-Based HIV Vaccine Candidate (MVA-gp145-GPN) Co-Expressing Clade C Membrane-Bound Trimeric gp145 Env and Gag-Induced Virus-Like Particles (VLPs) Triggered Broad and Multifunctional HIV-1-Specific T Cell and Antibody Responses. Viruses, 11.","DOI":"10.3390\/v11020160"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1056\/NEJMcibr1504232","article-title":"Viral Vectors Take on HIV Infection","volume":"373","author":"Mellins","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1080\/14760584.2017.1371594","article-title":"Immunogenicity and efficacy of DNA\/MVA HIV vaccines in rhesus macaque models","volume":"16","author":"Chea","year":"2017","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1586\/14760584.2016.1158108","article-title":"New developments in an old strategy: Heterologous vector primes and envelope protein boosts in HIV vaccine design","volume":"15","author":"Musich","year":"2016","journal-title":"Expert. Rev. Vaccines"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1093\/infdis\/jis670","article-title":"First-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD 001)","volume":"207","author":"Baden","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Baldassarri, S., Benati, D., D\u2019Alessio, F., Patrizi, C., Cattin, E., Gentile, M., Raggioli, A., and Recchia, A. (2022). Engineered Sleeping Beauty Transposon as Efficient System to Optimize Chimp Adenoviral Production. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147538"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e001046","DOI":"10.1136\/jitc-2020-001046","article-title":"Chimeric Ad5.F35 vector evades anti-adenovirus serotype 5 neutralization opposing GUCY2C-targeted antitumor immunity","volume":"8","author":"Flickinger","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"10847","DOI":"10.1073\/pnas.89.22.10847","article-title":"Nonreplicating vaccinia vector efficiently expresses recombinant genes","volume":"89","author":"Sutter","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.1128\/JVI.80.10.4705-4716.2006","article-title":"Expansion and diversification of virus-specific T cells following immunization of human immunodeficiency virus type 1 (HIV-1)-infected individuals with a recombinant modified vaccinia virus Ankara\/HIV-1 Gag vaccine","volume":"80","author":"Dorrell","year":"2006","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.1002\/eji.200636508","article-title":"Immunisation with recombinant modified vaccinia virus Ankara expressing HIV-1 gag in HIV-1-infected subjects stimulates broad functional CD4+ T cell responses","volume":"36","author":"Ondondo","year":"2006","journal-title":"Eur. J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1016\/j.vaccine.2007.01.005","article-title":"Safety and tolerability of recombinant modified vaccinia virus Ankara expressing an HIV-1 gag\/multiepitope immunogen (MVA.HIVA) in HIV-1-infected persons receiving combination antiretroviral therapy","volume":"25","author":"Dorrell","year":"2007","journal-title":"Vaccine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7490","DOI":"10.1128\/JVI.78.14.7490-7497.2004","article-title":"Heterologous envelope immunogens contribute to AIDS vaccine protection in rhesus monkeys","volume":"78","author":"Letvin","year":"2004","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e01193-20","DOI":"10.1128\/JVI.01193-20","article-title":"Priming with DNA Expressing Trimeric HIV V1V2 Alters the Immune Hierarchy Favoring the Development of V2-Specific Antibodies in Rhesus Macaques","volume":"95","author":"Devasundaram","year":"2020","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Hioe, C.E., Liu, X., Banin, A.N., Heindel, D.W., Klingler, J., Rao, P.G., Luo, C.C., Jiang, X., Pandey, S., and Ordonez, T. (2023). Vaccination with immune complexes modulates the elicitation of functional antibodies against HIV-1. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1271686"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Perdiguero, B., G\u00f3mez, C.E., Garc\u00eda-Arriaza, J., S\u00e1nchez-Corzo, C., Sorzano C\u00d3, S., Wilmschen, S., von Laer, D., Asbach, B., Schmalzl, C., and Peterhoff, D. (2019). Heterologous Combination of VSV-GP and NYVAC Vectors Expressing HIV-1 Trimeric gp145 Env as Vaccination Strategy to Induce Balanced B and T Cell Immune Responses. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02941"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez-Feliciano, J.A., Akamine, P., Cap\u00f3-V\u00e9lez, C.M., Delgado-V\u00e9lez, M., Dussupt, V., Krebs, S.J., Wojna, V., Polonis, V.R., Baerga-Ortiz, A., and Lasalde-Dominicci, J.A. (2020). A recombinant gp145 Env glycoprotein from HIV-1 expressed in two different cell lines: Effects on glycosylation and antigenicity. PLoS ONE, 15.","DOI":"10.1101\/2020.03.31.018408"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Akamine, P., Gonz\u00e1lez-Feliciano, J.A., Almod\u00f3var, R., Morell, G., Rivera, J., Cap\u00f3-V\u00e9lez, C.M., Delgado-V\u00e9lez, M., Prieto-Costas, L., Madera, B., and Eichinger, D. (2023). Optimizing the Production of gp145, an HIV-1 Envelope Glycoprotein Vaccine Candidate and Its Encapsulation in Guanosine Microparticles. Vaccines, 11.","DOI":"10.3390\/vaccines11050975"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"a007252","DOI":"10.1101\/cshperspect.a007252","article-title":"Vaccine design for CD8 T lymphocyte responses","volume":"1","author":"Koup","year":"2011","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_27","first-page":"170","article-title":"Study on Cellular Immune Responses of DNA Vaccine, rAd5 and rMVA Expressing SIV Gag\/Env Gene Combined Immunization in Mice","volume":"32","author":"He","year":"2016","journal-title":"Bing Du Xue Bao"},{"key":"ref_28","first-page":"113","article-title":"Infection of recombinant adenovirus Ad5F35-IL-12 in different kinds of human mononuclear macrophages","volume":"29","author":"Wang","year":"2013","journal-title":"Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Klatt, N.R., Shudo, E., Ortiz, A.M., Engram, J.C., Paiardini, M., Lawson, B., Miller, M.D., Else, J., Pandrea, I., and Estes, J.D. (2010). CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000747"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Crank, M.C., Wilson, E.M., Novik, L., Enama, M.E., Hendel, C.S., Gu, W., Nason, M.C., Bailer, R.T., Nabel, G.J., and McDermott, A.B. (2016). Safety and Immunogenicity of a rAd35-EnvA Prototype HIV-1 Vaccine in Combination with rAd5-EnvA in Healthy Adults (VRC 012). PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166393"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Keefer, M.C., Gilmour, J., Hayes, P., Gill, D., Kopycinski, J., Cheeseman, H., Cashin-Cox, M., Naarding, M., Clark, L., and Fernandez, N. (2012). A phase I double blind, placebo-controlled, randomized study of a multigenic HIV-1 adenovirus subtype 35 vector vaccine in healthy uninfected adults. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0041936"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/1\/79\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T05:25:04Z","timestamp":1767849904000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/1\/79"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,6]]},"references-count":31,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["v18010079"],"URL":"https:\/\/doi.org\/10.3390\/v18010079","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,6]]}}}