{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T21:08:03Z","timestamp":1774559283454,"version":"3.50.1"},"reference-count":121,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T00:00:00Z","timestamp":1568851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020","doi-asserted-by":"publisher","award":["681032"],"award-info":[{"award-number":["681032"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Extensive research on generating an efficient HIV vaccine is ongoing. A major aim of HIV vaccines is the induction of long-lasting, broadly neutralizing antibodies (bnAbs) that can confer sterile immunity for a prolonged period of time. Several strategies have been explored to reach this goal, i.e. protein immunization, DNA, or viral vectors, or a combination thereof. In this review, we give an overview of approaches using viral vectors for the induction of HIV-specific bnAbs. Many pre-clinical studies were performed using various replication-competent and -incompetent vectors. Amongst them, poxviral and adenoviral vectors were the most prevalent ones. In many studies, viral vectors were combined with a DNA prime or a protein boost. However, neutralizing antibodies were mainly induced against the homologous HIV-1 vaccine strain or tier 1 viruses, and in rare cases, against tier 2 viruses, indicating the need for improved antigens and vaccination strategies. Furthermore, we also review next generation Env antigens that are currently being used in protein vaccination approaches and point out how they could be utilized in viral vectors.<\/jats:p>","DOI":"10.3390\/vaccines7030119","type":"journal-article","created":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T11:02:01Z","timestamp":1568890921000},"page":"119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Viral Vectors for the Induction of Broadly Neutralizing Antibodies against HIV"],"prefix":"10.3390","volume":"7","author":[{"given":"Sarah","family":"Wilmschen","sequence":"first","affiliation":[{"name":"Division of Virology, Medical University of Innsbruck, Innsbruck 6020, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joern E.","family":"Schmitz","sequence":"additional","affiliation":[{"name":"Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-7905","authenticated-orcid":false,"given":"Janine","family":"Kimpel","sequence":"additional","affiliation":[{"name":"Division of Virology, Medical University of Innsbruck, Innsbruck 6020, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1542\/peds.40.5.798","article-title":"Experiences with Jeryl Lynn strain live attenuated mumps virus vaccine in a pediatric outpatient clinic","volume":"40","author":"Young","year":"1967","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1001\/jama.1968.03150030043009","article-title":"Development and evaluation of the Moraten measles virus vaccine","volume":"206","author":"Hilleman","year":"1968","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1017\/S0022172400021720","article-title":"Vaccination of adults with Wistar RA 27\/3 rubella vaccine","volume":"69","author":"Freestone","year":"1971","journal-title":"J. Hyg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1056\/NEJM198405313102201","article-title":"Live attenuated varicella virus vaccine. Efficacy trial in healthy children","volume":"310","author":"Weibel","year":"1984","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1586\/14760584.6.1.11","article-title":"Rotarix (RIX4414): An oral human rotavirus vaccine","volume":"6","year":"2007","journal-title":"Expert Rev. Vaccines"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1056\/NEJMoa065368","article-title":"Live attenuated versus inactivated influenza vaccine in infants and young children","volume":"356","author":"Belshe","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1016\/j.copbio.2007.10.010","article-title":"Replicating and non-replicating viral vectors for vaccine development","volume":"18","year":"2007","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cuevas, J.M., Geller, R., Garijo, R., Lopez-Aldeguer, J., and Sanjuan, R. (2015). Extremely High Mutation Rate of HIV-1 In Vivo. PLoS Biol., 13.","DOI":"10.1371\/journal.pbio.1002251"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/S0140-6736(08)61591-3","article-title":"Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): A double-blind, randomised, placebo-controlled, test-of-concept trial","volume":"372","author":"Buchbinder","year":"2008","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13439","DOI":"10.1073\/pnas.1400446111","article-title":"Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals","volume":"111","author":"Hu","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Hoot, S., McGuire, A.T., Cohen, K.W., Strong, R.K., Hangartner, L., Klein, F., Diskin, R., Scheid, J.F., Sather, D.N., and Burton, D.R. (2013). Recombinant HIV envelope proteins fail to engage germline versions of anti-CD4bs bNAbs. PLoS Pathog., 9.","DOI":"10.1371\/annotation\/ed7c0148-97eb-4416-824d-6e6d1aaeceef"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1128\/JVI.02108-09","article-title":"Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies","volume":"84","author":"Seaman","year":"2010","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1097\/00042560-200203010-00005","article-title":"Safety and immunogenicity of a high-titered canarypox vaccine in combination with rgp120 in a diverse population of HIV-1-uninfected adults: AIDS Vaccine Evaluation Group Protocol 022A","volume":"29","author":"Gupta","year":"2002","journal-title":"J. Acquir. Immune. Defic. Syndr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1086\/422258","article-title":"Safety and immunogenicity of an HIV subtype B and E prime-boost vaccine combination in HIV-negative Thai adults","volume":"190","author":"Nitayaphan","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1086\/368020","article-title":"Immunogenicity of a recombinant human immunodeficiency virus (HIV)-canarypox vaccine in HIV-seronegative Ugandan volunteers: Results of the HIV Network for Prevention Trials 007 Vaccine Study","volume":"187","author":"Cao","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2407","DOI":"10.1097\/00002030-199818000-00009","article-title":"Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers. NIAID AIDS Vaccine Evaluation Group","volume":"12","author":"Belshe","year":"1998","journal-title":"AIDS"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/infdis\/jis367","article-title":"Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials","volume":"206","author":"Montefiori","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1093\/infdis\/173.2.340","article-title":"Immunization with envelope subunit vaccine products elicits neutralizing antibodies against laboratory-adapted but not primary isolates of human immunodeficiency virus type 1. The National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group","volume":"173","author":"Mascola","year":"1996","journal-title":"J. Infect. Dis."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3324","DOI":"10.1016\/j.celrep.2018.08.051","article-title":"Rational Design of DNA-Expressed Stabilized Native-Like HIV-1 Envelope Trimers","volume":"24","author":"Aldon","year":"2018","journal-title":"Cell Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.chom.2018.05.002","article-title":"Interdomain Stabilization Impairs CD4 Binding and Improves Immunogenicity of the HIV-1 Envelope Trimer","volume":"23","author":"Zhang","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/j.immuni.2018.11.011","article-title":"Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers","volume":"50","author":"Pauthner","year":"2018","journal-title":"Immunity"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3681","DOI":"10.1016\/j.celrep.2017.12.028","article-title":"Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models","volume":"21","author":"Saunders","year":"2017","journal-title":"Cell Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sanders, R.W., Derking, R., Cupo, A., Julien, J.P., Yasmeen, A., de Val, N., Kim, H.J., Blattner, C., de la Pena, A.T., and Korzun, J. (2013). A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003618"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"aac4223","DOI":"10.1126\/science.aac4223","article-title":"HIV-1 VACCINES. HIV-1 neutralizing antibodies induced by native-like envelope trimers","volume":"349","author":"Sanders","year":"2015","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.celrep.2015.03.047","article-title":"Cleavage-independent HIV-1 Env trimers engineered as soluble native spike mimetics for vaccine design","volume":"11","author":"Sharma","year":"2015","journal-title":"Cell Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1088 e6","DOI":"10.1016\/j.immuni.2017.05.007","article-title":"Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches","volume":"46","author":"Pauthner","year":"2017","journal-title":"Immunity"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1038\/s41467-019-10262-5","article-title":"Structure and immunogenicity of a stabilized HIV-1 envelope trimer based on a group-M consensus sequence","volume":"10","author":"Sliepen","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bresk, C.A., Hofer, T., Wilmschen, S., Krismer, M., Beierfuss, A., Effantin, G., Weissenhorn, W., Hogan, M.J., Jordan, A.P.O., and Gelman, R.S. (2019). Induction of Tier 1 HIV Neutralizing Antibodies by Envelope Trimers Incorporated into a Replication Competent Vesicular Stomatitis Virus Vector. Viruses, 11.","DOI":"10.3390\/v11020159"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e01957-17","DOI":"10.1128\/JVI.01957-17","article-title":"Immunogenicity in Rabbits of HIV-1 SOSIP Trimers from Clades A, B, and C, Given Individually, Sequentially, or in Combination","volume":"92","author":"Sliepen","year":"2018","journal-title":"J. Virol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/nature12053","article-title":"Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus","volume":"496","author":"Liao","year":"2013","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1038\/s41467-017-01336-3","article-title":"Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations","volume":"8","author":"Williams","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1126\/science.aad9195","article-title":"HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen","volume":"351","author":"Jardine","year":"2016","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1126\/science.1234150","article-title":"Rational HIV immunogen design to target specific germline B cell receptors","volume":"340","author":"Jardine","year":"2013","journal-title":"Science"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1016\/j.xphs.2019.01.033","article-title":"Developability Assessment of Physicochemical Properties and Stability Profiles of HIV-1 BG505 SOSIP.664 and BG505 SOSIP.v4.1-GT1.1 gp140 Envelope Glycoprotein Trimers as Candidate Vaccine Antigens","volume":"108","author":"Whitaker","year":"2019","journal-title":"J. Pharm. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1084\/jem.20161160","article-title":"Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo","volume":"214","author":"Garces","year":"2017","journal-title":"J. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1038\/s41591-018-0042-6","article-title":"Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1","volume":"24","author":"Xu","year":"2018","journal-title":"Nat. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/sj.gt.3301137","article-title":"Effective repeat administration with adenovirus vectors to the muscle","volume":"7","author":"Chen","year":"2000","journal-title":"Gene Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5839","DOI":"10.1073\/pnas.0800280105","article-title":"Hybrid alphavirus-rhabdovirus propagating replicon particles are versatile and potent vaccine vectors","volume":"105","author":"Rose","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1089\/hum.2011.031","article-title":"Impact of pre-existing immunity on gene transfer to nonhuman primate liver with adeno-associated virus 8 vectors","volume":"22","author":"Wang","year":"2011","journal-title":"Hum. Gene Ther."},{"key":"ref_40","first-page":"351","article-title":"Prevalence of neutralizing antibodies to adenoviral serotypes 5 and 35 in the adult populations of The Gambia, South Africa, and the United States","volume":"11","author":"Nwanegbo","year":"2004","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/nrmicro3360","article-title":"Novel vaccine vectors for HIV-1","volume":"12","author":"Barouch","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s12977-018-0449-7","article-title":"Adeno-associated virus gene delivery of broadly neutralizing antibodies as prevention and therapy against HIV-1","volume":"15","author":"Lin","year":"2018","journal-title":"Retrovirology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/s41591-019-0412-8","article-title":"Broadly neutralizing anti-HIV-1 monoclonal antibodies in the clinic","volume":"25","author":"Caskey","year":"2019","journal-title":"Nat. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/nm.3471","article-title":"Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission","volume":"20","author":"Balazs","year":"2014","journal-title":"Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S2352-3018(19)30003-7","article-title":"Adeno-associated virus vectored immunoprophylaxis to prevent HIV in healthy adults: A phase 1 randomised controlled trial","volume":"6","author":"Priddy","year":"2019","journal-title":"Lancet HIV"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nbt.2618","article-title":"Broad protection against influenza infection by vectored immunoprophylaxis in mice","volume":"31","author":"Balazs","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/01.qai.0000248356.48501.ff","article-title":"Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: Negative results fail to trigger a phase 3 correlates trial","volume":"44","author":"Russell","year":"2007","journal-title":"J. Acquir. Immune Defic. Syndr"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e13579","DOI":"10.1371\/journal.pone.0013579","article-title":"Safety and immunogenicity of a replication-defective adenovirus type 5 HIV vaccine in Ad5-seronegative persons: A randomized clinical trial (HVTN 054)","volume":"5","author":"Peiperl","year":"2010","journal-title":"PLoS ONE"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S1473-3099(11)70098-6","article-title":"Safety and efficacy of the HVTN 503\/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: A double-blind, randomised, placebo-controlled test-of-concept phase 2b study","volume":"11","author":"Gray","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1056\/NEJMoa1113425","article-title":"Immune-correlates analysis of an HIV-1 vaccine efficacy trial","volume":"366","author":"Haynes","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Rabinovich, S., Powell, R.L., Lindsay, R.W., Yuan, M., Carpov, A., Wilson, A., Lopez, M., Coleman, J.W., Wagner, D., and Sharma, P. (2014). A novel, live-attenuated vesicular stomatitis virus vector displaying conformationally intact, functional HIV-1 envelope trimers that elicits potent cellular and humoral responses in mice. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106597"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.bbrc.2005.11.067","article-title":"Elicitation of neutralizing antibodies by intranasal administration of recombinant vesicular stomatitis virus expressing human immunodeficiency virus type 1 gp120","volume":"339","author":"Jiang","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1089\/aid.2004.20.989","article-title":"Immunogenicity of attenuated vesicular stomatitis virus vectors expressing HIV type 1 Env and SIV Gag proteins: Comparison of intranasal and intramuscular vaccination routes","volume":"20","author":"Egan","year":"2004","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"10903","DOI":"10.1128\/JVI.74.23.10903-10910.2000","article-title":"Glycoprotein exchange vectors based on vesicular stomatitis virus allow effective boosting and generation of neutralizing antibodies to a primary isolate of human immunodeficiency virus type 1","volume":"74","author":"Rose","year":"2000","journal-title":"J. Virol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.virol.2004.10.018","article-title":"Strong cellular and humoral anti-HIV Env immune responses induced by a heterologous rhabdoviral prime-boost approach","volume":"331","author":"Tan","year":"2005","journal-title":"Virology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3544","DOI":"10.1073\/pnas.97.7.3544","article-title":"Recombinant rabies virus as potential live-viral vaccines for HIV-1","volume":"97","author":"Schnell","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e02182-16","DOI":"10.1128\/JVI.02182-16","article-title":"HIV\/AIDS Vaccine Candidates Based on Replication-Competent Recombinant Poxvirus NYVAC-C-KC Expressing Trimeric gp140 and Gag-Derived Virus-Like Particles or Lacking the Viral Molecule B19 That Inhibits Type I Interferon Activate Relevant HIV-1-Specific B and T Cell Immune Functions in Nonhuman Primates","volume":"91","author":"Perdiguero","year":"2017","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"8525","DOI":"10.1128\/JVI.01265-15","article-title":"Head-to-Head Comparison of Poxvirus NYVAC and ALVAC Vectors Expressing Identical HIV-1 Clade C Immunogens in Prime-Boost Combination with Env Protein in Nonhuman Primates","volume":"89","author":"Perdiguero","year":"2015","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e01513-18","DOI":"10.1128\/JVI.01513-18","article-title":"Replication-Competent NYVAC-KC Yields Improved Immunogenicity to HIV-1 Antigens in Rhesus Macaques Compared to Nonreplicating NYVAC","volume":"93","author":"Kibler","year":"2019","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1097\/00002030-200011100-00005","article-title":"Cross-protection in NYVAC-HIV-1-immunized\/HIV-2-challenged but not in NYVAC-HIV-2-immunized\/SHIV-challenged rhesus macaques","volume":"14","author":"Patterson","year":"2000","journal-title":"AIDS"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1089\/aid.1996.12.985","article-title":"Multiple immunizations with attenuated poxvirus HIV type 2 recombinants and subunit boosts required for protection of rhesus macaques","volume":"12","author":"Myagkikh","year":"1996","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1089\/aid.1995.11.909","article-title":"Highly attenuated HIV type 2 recombinant poxviruses, but not HIV-2 recombinant Salmonella vaccines, induce long-lasting protection in rhesus macaques","volume":"11","author":"Franchini","year":"1995","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.1016\/j.vaccine.2012.04.075","article-title":"Broad HIV-1 neutralizing antibody response induced by heterologous gp140\/gp145 DNA prime-vaccinia boost immunization","volume":"30","author":"Liu","year":"2012","journal-title":"Vaccine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1742-4690-7-71","article-title":"Broader HIV-1 neutralizing antibody responses induced by envelope glycoprotein mutants based on the EIAV attenuated vaccine","volume":"7","author":"Liu","year":"2010","journal-title":"Retrovirology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1097\/QAD.0000000000000595","article-title":"HIV-1 vaccines based on replication-competent Tiantan vaccinia protected Chinese rhesus macaques from simian HIV infection","volume":"29","author":"Liu","year":"2015","journal-title":"AIDS"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"McCurley, N.P., Domi, A., Basu, R., Saunders, K.O., LaBranche, C.C., Montefiori, D.C., Haynes, B.F., and Robinson, H.L. (2017). HIV transmitted\/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0177863"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8842","DOI":"10.1128\/JVI.01163-16","article-title":"Virus-Like Particles Displaying Trimeric Simian Immunodeficiency Virus (SIV) Envelope gp160 Enhance the Breadth of DNA\/Modified Vaccinia Virus Ankara SIV Vaccine-Induced Antibody Responses in Rhesus Macaques","volume":"90","author":"Iyer","year":"2016","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1089\/0889222041217428","article-title":"Multiprotein HIV type 1 clade B DNA and MVA vaccines: Construction, expression, and immunogenicity in rodents of the MVA component","volume":"20","author":"Wyatt","year":"2004","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1016\/S0264-410X(02)00773-9","article-title":"Comparative analysis of immune responses and cytokine profiles elicited in rabbits by the combined use of recombinant fowlpox viruses, plasmids and virus-like particles in prime-boost vaccination protocols against SHIV","volume":"21","author":"Radaelli","year":"2003","journal-title":"Vaccine"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Zhang, X., Sobue, T., Isshiki, M., Makino, S.-i., Inoue, M., Kato, K., Shioda, T., Ohashi, T., Sato, H., and Komano, J. (2012). Elicitation of Both Anti HIV-1 Env Humoral and Cellular Immunities by Replicating Vaccinia Prime Sendai Virus Boost Regimen and Boosting by CD40Lm. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051633"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1006\/viro.1997.8478","article-title":"Screening of HIV-1 Env glycoproteins for the ability to raise neutralizing antibody using DNA immunization and recombinant vaccinia virus boosting","volume":"230","author":"Richmond","year":"1997","journal-title":"Virology"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Alexander, J., Mendy, J., Vang, L., Avanzini, J.B., Garduno, F., Manayani, D.J., Ishioka, G., Farness, P., Ping, L.H., and Swanstrom, R. (2013). Pre-clinical development of a recombinant, replication-competent adenovirus serotype 4 vector vaccine expressing HIV-1 envelope 1086 clade C. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0082380"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.virol.2014.10.001","article-title":"HIV-1 CD4-induced (CD4i) gp120 epitope vaccines promote B and T-cell responses that contribute to reduced viral loads in rhesus macaques","volume":"471","author":"Thomas","year":"2014","journal-title":"Virology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1111\/j.1600-0463.2006.apm_395.x","article-title":"Immune response in rhesus macaques after mixed modality immunisations with DNA, recombinant adenovirus and recombinant gp120 from human immunodeficiency virus type 1","volume":"114","author":"Vinner","year":"2006","journal-title":"APMIS"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"6516","DOI":"10.1128\/JVI.79.10.6516-6522.2005","article-title":"Replication-defective adenovirus serotype 5 vectors elicit durable cellular and humoral immune responses in nonhuman primates","volume":"79","author":"Santra","year":"2005","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1128\/JVI.79.2.771-779.2005","article-title":"Neutralizing antibodies elicited by immunization of monkeys with DNA plasmids and recombinant adenoviral vectors expressing human immunodeficiency virus type 1 proteins","volume":"79","author":"Mascola","year":"2005","journal-title":"J. Virol."},{"key":"ref_77","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_78","doi-asserted-by":"crossref","first-page":"e01092-17","DOI":"10.1128\/JVI.01092-17","article-title":"Combination Adenovirus and Protein Vaccines Prevent Infection or Reduce Viral Burden after Heterologous Clade C Simian-Human Immunodeficiency Virus Mucosal Challenge","volume":"92","author":"Malherbe","year":"2018","journal-title":"J. Virol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1097\/01.qai.0000230318.40170.60","article-title":"An adenovirus-based HIV subtype B prime\/boost vaccine regimen elicits antibodies mediating broad antibody-dependent cellular cytotoxicity against non-subtype B HIV strains","volume":"43","author":"Florese","year":"2006","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1089\/aid.1994.10.1443","article-title":"Immunogenicity of recombinant adenovirus-human immunodeficiency virus vaccines in chimpanzees following intranasal administration","volume":"10","author":"Lubeck","year":"1994","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"7777","DOI":"10.1073\/pnas.89.16.7777","article-title":"Adenovirus-human immunodeficiency virus (HIV) envelope recombinant vaccines elicit high-titered HIV-neutralizing antibodies in the dog model","volume":"89","author":"Natuk","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Capucci, S., Wee, E.G., Schiffner, T., LaBranche, C.C., Borthwick, N., Cupo, A., Dodd, J., Dean, H., Sattentau, Q., and Montefiori, D. (2017). HIV-1-neutralizing antibody induced by simian adenovirus and poxvirus MVA-vectored BG505 native-like envelope trimers. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181886"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nature10766","article-title":"Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys","volume":"482","author":"Barouch","year":"2012","journal-title":"Nature"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nm.2089","article-title":"Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys","volume":"16","author":"Barouch","year":"2010","journal-title":"Natl. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.cell.2013.09.061","article-title":"Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys","volume":"155","author":"Barouch","year":"2013","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1089\/104303401750214276","article-title":"A Novel Recombinant Adeno-Associated Virus Vaccine Induces a Long-Term Humoral Immune Response to Human Immunodeficiency Virus","volume":"12","author":"Xin","year":"2001","journal-title":"Hum. Gene Ther."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"12738","DOI":"10.1128\/JVI.01441-09","article-title":"A new genetic vaccine platform based on an adeno-associated virus isolated from a rhesus macaque","volume":"83","author":"Lin","year":"2009","journal-title":"J. Virol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1128\/JVI.02847-15","article-title":"Enhanced Immune Responses to HIV-1 Envelope Elicited by a Vaccine Regimen Consisting of Priming with Newcastle Disease Virus Expressing HIV gp160 and Boosting with gp120 and SOSIP gp140 Proteins","volume":"90","author":"Khattar","year":"2016","journal-title":"J. Virol."},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Khattar, S.K., Samal, S., LaBranche, C.C., Montefiori, D.C., Collins, P.L., and Samal, S.K. (2013). Comparative immunogenicity of HIV-1 gp160, gp140 and gp120 expressed by live attenuated newcastle disease virus vector. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078521"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1128\/JVI.78.1.146-157.2004","article-title":"A single injection of recombinant measles virus vaccines expressing human immunodeficiency virus (HIV) type 1 clade B envelope glycoproteins induces neutralizing antibodies and cellular immune responses to HIV","volume":"78","author":"Lorin","year":"2004","journal-title":"J. Virol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.jviromet.2017.08.012","article-title":"Development of a recombinant yellow fever vector expressing a HIV clade C founder envelope gp120","volume":"249","author":"Yu","year":"2017","journal-title":"J. Virol. Methods"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1038\/mt.2016.123","article-title":"Immunization with an SIV-based IDLV Expressing HIV-1 Env 1086 Clade C Elicits Durable Humoral and Cellular Responses in Rhesus Macaques","volume":"24","author":"Negri","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5166","DOI":"10.1016\/j.vaccine.2018.07.010","article-title":"Live rubella vectors can express native HIV envelope glycoproteins targeted by broadly neutralizing antibodies and prime the immune response to an envelope protein boost","volume":"36","author":"Virnik","year":"2018","journal-title":"Vaccine"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1038\/339385a0","article-title":"An engineered poliovirus chimaera elicits broadly reactive HIV-1 neutralizing antibodies","volume":"339","author":"Evans","year":"1989","journal-title":"Nature"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"10902","DOI":"10.1128\/JVI.79.17.10902-10914.2005","article-title":"Biochemical and immunogenic characterization of soluble human immunodeficiency virus type 1 envelope glycoprotein trimers expressed by semliki forest virus","volume":"79","author":"Forsell","year":"2005","journal-title":"J. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Crosby, C.M., and Barry, M.A. (2017). Transgene Expression and Host Cell Responses to Replication-Defective, Single-Cycle, and Replication-Competent Adenovirus Vectors. Genes, 8.","DOI":"10.3390\/genes8020079"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1007\/s00109-012-0863-6","article-title":"Semireplication-competent vesicular stomatitis virus as a novel platform for oncolytic virotherapy","volume":"90","author":"Muik","year":"2012","journal-title":"J. Mol. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1099\/0022-1317-72-5-1031","article-title":"Mapping of deletions in the genome of the highly attenuated vaccinia virus MVA and their influence on virulence","volume":"72","author":"Meyer","year":"1991","journal-title":"J. Gen. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0042-6822(92)90752-B","article-title":"NYVAC: A highly attenuated strain of vaccinia virus","volume":"188","author":"Tartaglia","year":"1992","journal-title":"Virology"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1128\/JVI.76.3.1309-1327.2002","article-title":"Relative neurotropism of a recombinant rhabdovirus expressing a green fluorescent envelope glycoprotein","volume":"76","author":"Dalton","year":"2002","journal-title":"J. Virol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e00479-17","DOI":"10.1128\/JVI.00479-17","article-title":"Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice","volume":"91","author":"Lennemann","year":"2017","journal-title":"J. Virol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"5679","DOI":"10.1128\/JVI.02511-10","article-title":"Pseudotyping vesicular stomatitis virus with lymphocytic choriomeningitis virus glycoproteins enhances infectivity for glioma cells and minimizes neurotropism","volume":"85","author":"Muik","year":"2011","journal-title":"J. Virol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.cell.2013.03.018","article-title":"Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization","volume":"153","author":"Klein","year":"2013","journal-title":"Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"10383","DOI":"10.1128\/JVI.01653-15","article-title":"Murine Antibody Responses to Cleaved Soluble HIV-1 Envelope Trimers Are Highly Restricted in Specificity","volume":"89","author":"Hu","year":"2015","journal-title":"J. Virol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"6639","DOI":"10.1073\/pnas.1606050113","article-title":"Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination","volume":"113","author":"Tam","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.cell.2019.04.012","article-title":"Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance","volume":"177","author":"Cirelli","year":"2019","journal-title":"Cell"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.coi.2017.06.008","article-title":"Germinal center enhancement by extended antigen availability","volume":"47","author":"Cirelli","year":"2017","journal-title":"Curr. Opin. Immunol."},{"key":"ref_108","first-page":"w14465","article-title":"Virally vectored vaccine delivery: Medical needs, mechanisms, advantages and challenges","volume":"147","author":"Pinschewer","year":"2017","journal-title":"Swiss Med. Wkly."},{"key":"ref_109","first-page":"273","article-title":"Subversion of host defense mechanisms by adenoviruses","volume":"269","author":"Burgert","year":"2002","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Lundstrom, K. (2018). Viral Vectors in Gene Therapy. Diseases, 6.","DOI":"10.3390\/diseases6020042"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"5911","DOI":"10.1128\/jvi.67.10.5911-5921.1993","article-title":"Packaging capacity and stability of human adenovirus type 5 vectors","volume":"67","author":"Bett","year":"1993","journal-title":"J. Virol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1128\/JVI.01644-08","article-title":"DNA genome size affects the stability of the adenovirus virion","volume":"83","author":"Smith","year":"2009","journal-title":"J. Virol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1016\/j.vaccine.2006.09.090","article-title":"Head-to-head comparison on the immunogenicity of two HIV\/AIDS vaccine candidates based on the attenuated poxvirus strains MVA and NYVAC co-expressing in a single locus the HIV-1BX08 gp120 and HIV-1IIIB Gag-Pol-Nef proteins of clade B","volume":"25","author":"Wagner","year":"2007","journal-title":"Vaccine"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"7642","DOI":"10.1128\/JVI.76.15.7642-7650.2002","article-title":"Adding genes to the RNA genome of vesicular stomatitis virus: Positional effects on stability of expression","volume":"76","author":"Wertz","year":"2002","journal-title":"J. Virol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1038\/s41467-017-01549-6","article-title":"Structure-based design of native-like HIV-1 envelope trimers to silence non-neutralizing epitopes and eliminate CD4 binding","volume":"8","author":"Kulp","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1097\/COH.0000000000000362","article-title":"Lessons learned from human HIV vaccine trials","volume":"12","author":"Pollara","year":"2017","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1128\/JVI.02664-13","article-title":"Mechanism of HIV-1 neutralization by antibodies targeting a membrane-proximal region of gp41","volume":"88","author":"Chen","year":"2014","journal-title":"J. Virol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"38177","DOI":"10.1038\/srep38177","article-title":"Structural basis for broad neutralization of HIV-1 through the molecular recognition of 10E8 helical epitope at the membrane interface","volume":"6","author":"Rujas","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e01005","DOI":"10.1128\/mBio.01005-15","article-title":"Mucosal Immunization with Newcastle Disease Virus Vector Coexpressing HIV-1 Env and Gag Proteins Elicits Potent Serum, Mucosal, and Cellular Immune Responses That Protect against Vaccinia Virus Env and Gag Challenges","volume":"6","author":"Khattar","year":"2015","journal-title":"MBio"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/280147a0","article-title":"T cells primed by influenza virion internal components can cooperate in the antibody response to haemagglutinin","volume":"280","author":"Russell","year":"1979","journal-title":"Nature"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/1742-4690-10-117","article-title":"GagPol-specific CD4(+) T-cells increase the antibody response to Env by intrastructural help","volume":"10","author":"Nabi","year":"2013","journal-title":"Retrovirology"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/3\/119\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:21:55Z","timestamp":1760188915000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/7\/3\/119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,19]]},"references-count":121,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["vaccines7030119"],"URL":"https:\/\/doi.org\/10.3390\/vaccines7030119","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,19]]}}}