{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T16:35:59Z","timestamp":1787589359157,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T00:00:00Z","timestamp":1580256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>The HIV-1 envelope glycoprotein (Env) is present on the surface of the virion at a very low density compared to most other enveloped viruses. Substitution of various parts of the stalk domain of Env (gp41) with the corresponding elements from other viral glycoproteins has been shown to increase Env spike density on the cell membrane and surface of virus-like particles (VLPs). In this study, chimeric Env antigens were generated by replacing the transmembrane and cytoplasmic domains of HIV-1 Env with the corresponding regions from the influenza H5 hemagglutinin (HA) (gp140HA2tr) and by replacing the entire gp41 region of Env with the HA2 subunit of HA (gp120HA2). Recombinant DNA and modified vaccinia Ankara (MVA) vaccines expressing HIV-1 subtype C mosaic Gag and gp150 Env or either of the chimeras were generated. Surprisingly, no significant differences were found in the levels of expression of gp150 Env or either of the chimeras on the surface of cells or on Gag VLPs. Differences were, however, observed in the binding of different monoclonal antibodies to the HIV-1 Env. Monoclonal antibodies, which recognized a V1 \/ V2 quaternary epitope at the tip of the native Env trimer, bound gp150 and gp140HA2tr chimera but failed to bind to the gp120HA2 chimera. Autologous Tier 2 neutralizing antibodies (NAbs) were produced by rabbits inoculated with DNA and MVA vaccines expressing the gp140HA2tr chimera or gp150 Env, but not those immunized with the gp120HA2 Env. These results showed that the addition of an HA2 stalk to HIV-1 gp120 did not improve immunogenicity, but rather that the full-length gp150 was required for optimal presentation of epitopes for the elicitation of a neutralizing antibody response to HIV-1.<\/jats:p>","DOI":"10.3390\/vaccines8010054","type":"journal-article","created":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T10:51:07Z","timestamp":1580295067000},"page":"54","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Immunogenicity of HIV-1 Vaccines Expressing Chimeric Envelope Glycoproteins on the Surface of Pr55 Gag Virus-Like Particles"],"prefix":"10.3390","volume":"8","author":[{"given":"Rosamund","family":"Chapman","sequence":"first","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa"},{"name":"Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michiel","family":"van Diepen","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa"},{"name":"Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shireen","family":"Galant","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa"},{"name":"Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Kruse","sequence":"additional","affiliation":[{"name":"Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Margolin","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa"},{"name":"Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa"},{"name":"Biopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, Cape Town 7701, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phindile","family":"Ximba","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa"},{"name":"Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tandile","family":"Hermanus","sequence":"additional","affiliation":[{"name":"Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa"},{"name":"Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2050, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penny","family":"Moore","sequence":"additional","affiliation":[{"name":"Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa"},{"name":"Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2050, South Africa"},{"name":"Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, Durban 4013, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8929-6279","authenticated-orcid":false,"given":"Nicola","family":"Douglass","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa"},{"name":"Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lise","family":"Williamson","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa"},{"name":"Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8024-9911","authenticated-orcid":false,"given":"Edward","family":"Rybicki","sequence":"additional","affiliation":[{"name":"Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa"},{"name":"Biopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, Cape Town 7701, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,29]]},"reference":[{"key":"ref_1","unstructured":"UNAIDS (2019, December 26). Global HIV & AIDs Stastics - 2019 Fact Sheet. Available online: https:\/\/www.unaids.org\/en\/resources\/fact-sheet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.chom.2018.06.012","article-title":"Immune Correlate-Guided HIV Vaccine Design","volume":"24","author":"Alter","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Schiller, J., and Chackerian, B. (2014). Why HIV virions have low numbers of envelope spikes: implications for vaccine development. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004254"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0167-5699(96)10066-9","article-title":"The influence of virus structure on antibody responses and virus serotype formation","volume":"17","author":"Bachmann","year":"1996","journal-title":"Immunol. Today"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1586\/14760584.6.3.381","article-title":"Virus-like particles: flexible platforms for vaccine development","volume":"6","author":"Chackerian","year":"2007","journal-title":"Expert Rev. Vaccines"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1016\/j.celrep.2016.04.078","article-title":"High-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells","volume":"15","author":"Ingale","year":"2016","journal-title":"Cell Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6775","DOI":"10.1128\/JVI.78.13.6775-6785.2004","article-title":"Modulation of Env content in virions of simian immunodeficiency virus: correlation with cell surface expression and virion infectivity","volume":"78","author":"Yuste","year":"2004","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1006\/viro.1997.8668","article-title":"Recombinant human immunodeficiency Pr55gag virus-like particles presenting chimeric envelope glycoproteins induce cytotoxic T-cells and neutralizing antibodies","volume":"235","author":"Deml","year":"1997","journal-title":"Virology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.virol.2015.09.015","article-title":"Effects of modification of the HIV-1 Env cytoplasmic tail on immunogenicity of VLP vaccines","volume":"489","author":"Vzorov","year":"2016","journal-title":"Virology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10869","DOI":"10.1128\/JVI.00542-07","article-title":"Incorporation of high levels of chimeric human immunodeficiency virus envelope glycoproteins into virus-like particles","volume":"81","author":"Wang","year":"2007","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4903","DOI":"10.1016\/j.vaccine.2011.05.005","article-title":"Generation of HIV-1 Virus-Like Particles expressing different HIV-1 glycoproteins","volume":"29","author":"Visciano","year":"2011","journal-title":"Vaccine"},{"key":"ref_12","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_13","doi-asserted-by":"crossref","unstructured":"Van Diepen, M.T., Chapman, R., Douglass, N., Galant, S., Moore, P.L., Margolin, E., Ximba, P., Morris, L., Rybicki, E.P., and Williamson, A.L. (2019). Prime-Boost Immunizations with DNA, Modified Vaccinia Virus Ankara, and Protein-Based Vaccines Elicit Robust HIV-1 Tier 2 Neutralizing Antibodies against the CAP256 Superinfecting Virus. J. Virol., 93.","DOI":"10.1128\/JVI.02155-18"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1038\/nm.3963","article-title":"Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies","volume":"21","author":"Bhiman","year":"2015","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nsmb.3144","article-title":"Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design","volume":"23","author":"Gorman","year":"2016","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4882","DOI":"10.1128\/JVI.03424-12","article-title":"Multiple pathways of escape from HIV broadly cross-neutralizing V2-dependent antibodies","volume":"87","author":"Moore","year":"2013","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/1743-422X-8-51","article-title":"The porcine circovirus type 1 capsid gene promoter improves antigen expression and immunogenicity in a HIV-1 plasmid vaccine","volume":"8","author":"Tanzer","year":"2011","journal-title":"Virology journal"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Chapman, R., Jongwe, T.I., Douglass, N., Chege, G., and Williamson, A.L. (2017). Heterologous prime-boost vaccination with DNA and MVA vaccines, expressing HIV-1 subtype C mosaic Gag virus-like particles, is highly immunogenic in mice. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0173352"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Jongwe, T.I., Chapman, R., Douglass, N., Chetty, S., Chege, G., and Williamson, A.L. (2016). HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159141"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/j.mex.2019.04.013","article-title":"Method to identify efficiently cleaved, membrane-bound, functional HIV-1 (Human Immunodeficiency Virus-1) envelopes","volume":"6","author":"Samal","year":"2019","journal-title":"MethodsX"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nature10696","article-title":"Structure of HIV-1 gp120 V1\/V2 domain with broadly neutralizing antibody PG9","volume":"480","author":"McLellan","year":"2011","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Van Diepen, M.T., Chapman, R., Moore, P.L., Margolin, E., Hermanus, T., Morris, L., Ximba, P., Rybicki, E.P., and Williamson, A.L. (2018). The adjuvant AlhydroGel elicits higher antibody titres than AddaVax when combined with HIV-1 subtype C gp140 from CAP256. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208310"},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"8875","DOI":"10.1128\/JVI.76.17.8875-8889.2002","article-title":"Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1","volume":"76","author":"Sanders","year":"2002","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8098","DOI":"10.1128\/JVI.00966-10","article-title":"Crystal structure of PG16 and chimeric dissection with somatically related PG9: structure-function analysis of two quaternary-specific antibodies that effectively neutralize HIV-1","volume":"84","author":"Pancera","year":"2010","journal-title":"J. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4578","DOI":"10.1128\/JVI.02585-10","article-title":"Immunotypes of a quaternary site of HIV-1 vulnerability and their recognition by antibodies","volume":"85","author":"Wu","year":"2011","journal-title":"J. Virol."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.immuni.2015.10.014","article-title":"Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design","volume":"43","author":"Andrabi","year":"2015","journal-title":"Immunity"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1038\/nsmb.2600","article-title":"Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16","volume":"20","author":"Pancera","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature13036","article-title":"Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies","volume":"509","author":"Schramm","year":"2014","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3128","DOI":"10.1128\/JVI.02658-10","article-title":"Potent and broad neutralization of HIV-1 subtype C by plasma antibodies targeting a quaternary epitope including residues in the V2 loop","volume":"85","author":"Moore","year":"2011","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Stano, A., Leaman, D.P., Kim, A.S., Zhang, L., Autin, L., Ingale, J., Gift, S.K., Truong, J., Wyatt, R.T., and Olson, A.J. (2017). Dense Array of Spikes on HIV-1 Virion Particles. J. Virol., 91.","DOI":"10.1128\/JVI.00415-17"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s00253-011-3297-0","article-title":"Improved expression of secretory and trimeric proteins in mammalian cells via the introduction of a new trimer motif and a mutant of the tPA signal sequence","volume":"91","author":"Wang","year":"2011","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4531","DOI":"10.1016\/j.vaccine.2005.08.023","article-title":"Relative contributions of codon usage, promoter efficiency and leader sequence to the antigen expression and immunogenicity of HIV-1 Env DNA vaccine","volume":"24","author":"Wang","year":"2006","journal-title":"Vaccine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.3389\/fimmu.2018.01116","article-title":"Cleavage-Independent HIV-1 Trimers From CHO Cell Lines Elicit Robust Autologous Tier 2 Neutralizing Antibodies","volume":"9","author":"Bale","year":"2018","journal-title":"Front Immunol."},{"key":"ref_36","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"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/1\/54\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T08:53:02Z","timestamp":1760172782000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/8\/1\/54"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,29]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,3]]}},"alternative-id":["vaccines8010054"],"URL":"https:\/\/doi.org\/10.3390\/vaccines8010054","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,29]]}}}