{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T01:55:17Z","timestamp":1781315717425,"version":"3.54.1"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100032516","name":"University of Minnesota Medical School","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100032516","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Graduate School at the University of Minnesota"},{"DOI":"10.13039\/100007249","name":"University of Minnesota","doi-asserted-by":"crossref","award":["#220347"],"award-info":[{"award-number":["#220347"]}],"id":[{"id":"10.13039\/100007249","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: The development of an effective HIV-1 vaccine remains a major challenge due to HIV-1\u2019s extraordinary diversity, high mutation rate, and the rarity of broadly neutralizing antibody (bnAb) precursors. To address these challenges, we have previously immunized rabbits with mRNA-LNPs encoding for HIV-1 envelope glycoproteins (Envs), together with mRNA-LNPs encoding for HIV-1 Gag, which likely mediated the generation of virus-like particles presenting HIV-1 Envs to the immune system in vivo. Methods: Here, we investigated whether an escalating dose (ED) immunization using mRNA-LNP priming, followed by boosts with synthetic, protein-based, virus-like particles (synVLPs) displaying HIV-1 SOSIP trimers via SpyTag\/SpyCatcher conjugation (group 1), could improve the quality and durability of the antibody responses compared to conventional bolus immunization (group 2). Previous studies have shown that, in contrast to single bolus immunization, the ED priming strategy could enhance B cell activation and prolong affinity maturation, resulting in higher-quality antibody responses. Results: Upon vaccination, rabbits from both groups developed strong homologous anti-Env antibody responses, with an increasing ability of sera from immunized rabbits to bind Envs following subsequent boosts. Antibodies in rabbit sera bound heterologous Envs, but there was no statistically significant difference in binding between the two groups. Overall, antibody responses were comparable across all animals and declined similarly over time in both groups, indicating that neither the adjuvants nor the ED priming led to any marked differences within this small sample size. Neutralization activity against homologous tier-2 HIV-1AD8 (mRNA prime) and tier-2 HIV-11059 (protein boost) was generally low across both groups; however, a higher neutralization titer was observed for the ED group against HIV-1AD8 following the final boost. One of the rabbits from the bolus group exhibited exceptionally high neutralization titers that correlated with elevated Env-specific binding against HIV-11059. Conclusions: These results highlight the challenges in eliciting broad and potent neutralizing antibody (nAb) responses. Our findings underscore the need for the continued development and refinement of immunogen design and delivery strategies to guide the elicitation of nAb.<\/jats:p>","DOI":"10.3390\/vaccines13111161","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T09:06:36Z","timestamp":1763111196000},"page":"1161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evaluating the Immune Response in Rabbits to an Escalating Dose of mRNA-Based HIV-1 Env Immunogens"],"prefix":"10.3390","volume":"13","author":[{"given":"Shamim","family":"Ahmed","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Durgadevi","family":"Parthasarathy","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tashina C.","family":"Picard","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2074-2373","authenticated-orcid":false,"given":"Gary R.","family":"Matyas","sequence":"additional","affiliation":[{"name":"U.S. Military HIV Research Program, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9553-4969","authenticated-orcid":false,"given":"Mangala","family":"Rao","sequence":"additional","affiliation":[{"name":"U.S. Military HIV Research Program, Center for Infectious Diseases Research, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alon","family":"Herschhorn","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, USA"},{"name":"Microbiology, Immunology, and Cancer Biology Graduate Program, The College of Veterinary Medicine Graduate Program, and the Molecular Pharmacology and Therapeutics Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,14]]},"reference":[{"key":"ref_1","unstructured":"HIV Data and Statistics. Available online: https:\/\/www.who.int\/teams\/global-hiv-hepatitis-and-stis-programmes\/hiv\/strategic-information\/hiv-data-and-statistics."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMoa0908492","article-title":"Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand","volume":"361","author":"Pitisuttithum","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/S1473-3099(12)70088-9","article-title":"Risk behaviour and time as covariates for efficacy of the HIV vaccine regimen ALVAC-HIV (vCP1521) and AIDSVAX B\/E: A post-hoc analysis of the Thai phase 3 efficacy trial RV 144","volume":"12","author":"Robb","year":"2012","journal-title":"Lancet Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Akapirat, S., Karnasuta, C., Vasan, S., Rerks-Ngarm, S., Pitisuttithum, P., Madnote, S., Savadsuk, H., Rittiroongrad, S., Puangkaew, J., and Phogat, S. (2018). Characterization of HIV-1 gp120 antibody specificities induced in anogenital secretions of RV144 vaccine recipients after late boost immunizations. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196397"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Gottardo, R., Bailer, R.T., Korber, B.T., Gnanakaran, S., Phillips, J., Shen, X., Tomaras, G.D., Turk, E., Imholte, G., and Eckler, L. (2013). Plasma IgG to linear epitopes in the V2 and V3 regions of HIV-1 gp120 correlate with a reduced risk of infection in the RV144 vaccine efficacy trial. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075665"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"eaax1880","DOI":"10.1126\/scitranslmed.aax1880","article-title":"Immune correlates of the Thai RV144 HIV vaccine regimen in South Africa","volume":"11","author":"Gray","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Dommaraju, K., Kijak, G., Carlson, J.M., Larsen, B.B., Tovanabutra, S., Geraghty, D.E., Deng, W., Maust, B.S., Edlefsen, P.T., and Sanders-Buell, E. (2014). CD8 and CD4 Epitope Predictions in RV144: No Strong Evidence of a T-Cell Driven Sieve Effect in HIV-1 Breakthrough Sequences from Trial Participants. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0111334"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8242","DOI":"10.1128\/JVI.01164-14","article-title":"Analysis of HLA A*02 Association with Vaccine Efficacy in the RV144 HIV-1 Vaccine Trial","volume":"88","author":"Gartland","year":"2014","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1016\/j.vaccine.2016.09.053","article-title":"Predictors of durable immune responses six months after the last vaccination in preventive HIV vaccine trials","volume":"35","author":"Huang","year":"2017","journal-title":"Vaccine"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Pitisuttithum, P., Rerks-Ngarm, S., Bussaratid, V., Dhitavat, J., Maekanantawat, W., Pungpak, S., Suntharasamai, P., Vanijanonta, S., Nitayapan, S., and Kaewkungwal, J. (2011). Safety and Reactogenicity of Canarypox ALVAC-HIV (vCP1521) and HIV-1 gp120 AIDSVAX B\/E Vaccination in an Efficacy Trial in Thailand. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027837"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhao, L.P., Fiore-Gartland, A., Carpp, L.N., Cohen, K.W., Rouphael, N., Fleurs, L., Dintwe, O., Zhao, M., Moodie, Z., and Fong, Y. (2020). Landscapes of binding antibody and T-cell responses to pox-protein HIV vaccines in Thais and South Africans. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0226803"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zolla-Pazner, S., deCamp, A., Gilbert, P.B., Williams, C., Yates, N.L., Williams, W.T., Howington, R., Fong, Y., Morris, D.E., and Soderberg, K.A. (2014). Vaccine-Induced IgG Antibodies to V1V2 Regions of Multiple HIV-1 Subtypes Correlate with Decreased Risk of HIV-1 Infection. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087572"},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.molmed.2024.05.017","article-title":"Insights from HIV-1 vaccine and passive immunization efficacy trials","volume":"30","author":"Ahmed","year":"2024","journal-title":"Trends Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4828","DOI":"10.1128\/JVI.00198-11","article-title":"The Neutralization Breadth of HIV-1 Develops Incrementally over Four Years and Is Associated with CD4+ T Cell Decline and High Viral Load during Acute Infection","volume":"85","author":"Gray","year":"2011","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1097\/QAD.0000000000000106","article-title":"Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection","volume":"28","author":"Hraber","year":"2014","journal-title":"AIDS"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Mikell, I., Sather, D.N., Kalams, S.A., Altfeld, M., Alter, G., and Stamatatos, L. (2011). Characteristics of the Earliest Cross-Neutralizing Antibody Response to HIV-1. PLOS Pathog., 7.","DOI":"10.1371\/annotation\/8b3b24b5-d4ed-483a-b233-0a88513ad499"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7337","DOI":"10.1128\/JVI.00110-09","article-title":"Human Immunodeficiency Virus Type 1 Elite Neutralizers: Individuals with Broad and Potent Neutralizing Activity Identified by Using a High-Throughput Neutralization Assay together with an Analytical Selection Algorithm","volume":"83","author":"Simek","year":"2009","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11502","DOI":"10.1128\/JVI.05363-11","article-title":"Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals","volume":"85","author":"Tomaras","year":"2011","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nchembio.1623","article-title":"A broad HIV-1 inhibitor blocks envelope glycoprotein transitions critical for entry","volume":"10","author":"Herschhorn","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e01598-16","DOI":"10.1128\/mBio.01598-16","article-title":"Release of gp120 Restraints Leads to an Entry-Competent Intermediate State of the HIV-1 Envelope Glycoproteins","volume":"7","author":"Herschhorn","year":"2016","journal-title":"mBio"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s44298-024-00082-w","article-title":"Incompletely closed HIV-1CH040 envelope glycoproteins resist broadly neutralizing antibodies while mediating efficient HIV-1 entry","volume":"3","author":"Parthasarathy","year":"2025","journal-title":"Npj Viruses"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev-immunol-041015-055515","article-title":"Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design","volume":"34","author":"Burton","year":"2016","journal-title":"Annu. Rev. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"eaaz2686","DOI":"10.1126\/scitranslmed.aaz2686","article-title":"Multiple roles for HIV broadly neutralizing antibodies","volume":"11","author":"Haynes","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1021\/acsinfecdis.2c00573","article-title":"Indirect Mechanisms of HIV-1 Evasion from Broadly Neutralizing Antibodies In Vivo","volume":"9","author":"Herschhorn","year":"2023","journal-title":"ACS Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5014","DOI":"10.1128\/JVI.02785-13","article-title":"Loss of a Conserved N-Linked Glycosylation Site in the Simian Immunodeficiency Virus Envelope Glycoprotein V2 Region Enhances Macrophage Tropism by Increasing CD4-Independent Cell-to-Cell Transmission","volume":"88","author":"Yen","year":"2014","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1038\/s41586-022-05216-9","article-title":"Long-primed germinal centres with enduring affinity maturation and clonal migration","volume":"609","author":"Lee","year":"2022","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1146\/annurev-immunol-020711-075032","article-title":"Germinal Centers","volume":"30","author":"Victora","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1146\/annurev-immunol-120419-022408","article-title":"Germinal Centers","volume":"40","author":"Victora","year":"2022","journal-title":"Annu. Rev. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1073","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_31","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.immuni.2017.11.023","article-title":"Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens","volume":"48","author":"Abbott","year":"2018","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/imr.12512","article-title":"Tfh cells and HIV bnAbs, an immunodominance model of the HIV neutralizing antibody generation problem","volume":"275","author":"Lee","year":"2017","journal-title":"Immunol. Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"E6639","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."},{"key":"ref_34","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_35","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":"2019","journal-title":"Immunity"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41541-024-00818-y","article-title":"Exploring synergies between B- and T-cell vaccine approaches to optimize immune responses against HIV\u2014Workshop report","volume":"9","author":"Maciel","year":"2024","journal-title":"npj Vaccines"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10844","DOI":"10.1038\/ncomms10844","article-title":"Elimination of HIV-1-infected cells by broadly neutralizing antibodies","volume":"7","author":"Bruel","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41392-023-01471-y","article-title":"T cells in health and disease","volume":"8","author":"Sun","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"eady6831","DOI":"10.1126\/scitranslmed.ady6831","article-title":"Vaccination with mRNA-encoded membrane-anchored HIV envelope trimers elicited tier 2 neutralizing antibodies in a phase 1 clinical trial","volume":"17","author":"Parks","year":"2025","journal-title":"Sci. Transl. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41541-023-00774-z","article-title":"Enhancing anti-viral neutralization response to immunization with HIV-1 envelope glycoprotein immunogens","volume":"8","author":"Ahmed","year":"2023","journal-title":"npj Vaccines"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1038\/s41591-021-01574-5","article-title":"A multiclade env-gag VLP mRNA vaccine elicits tier-2 HIV-1-neutralizing antibodies and reduces the risk of heterologous SHIV infection in macaques","volume":"27","author":"Zhang","year":"2021","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e00041-24","DOI":"10.1128\/cmr.00041-24","article-title":"mRNA-based HIV-1 vaccines","volume":"37","author":"Ahmed","year":"2024","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1080\/14760584.2020.1745636","article-title":"Army Liposome Formulation (ALF) Family of Vaccine Adjuvants","volume":"19","author":"Alving","year":"2020","journal-title":"Expert Rev. Vaccines"},{"key":"ref_44","unstructured":"The Adjuvant MF59: A 10-Year Perspective Gary Ott, Ramachandran Radhakrishnan|Springer Nature Experiments. Available online: https:\/\/experiments.springernature.com\/articles\/10.1385\/1-59259-083-7:211."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1016\/j.vaccine.2013.05.007","article-title":"The adjuvant effect of MF59 is due to the oil-in-water emulsion formulation, none of the individual components induce a comparable adjuvant effect","volume":"31","author":"Calabro","year":"2013","journal-title":"Vaccine"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/978-1-4615-1823-5_10","article-title":"MF59: Design and evaluation of a safe and potent adjuvant for human vaccines","volume":"6","author":"Ott","year":"1995","journal-title":"Pharm. Biotechnol."},{"key":"ref_47","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 Pe\u00f1a, 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_48","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/anie.202009663","article-title":"Overcoming Symmetry Mismatch in Vaccine Nanoassembly through Spontaneous Amidation","volume":"60","author":"Rahikainen","year":"2021","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7334","DOI":"10.1038\/s41467-024-51656-4","article-title":"Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted\/founder sensitivity to broadly neutralizing antibodies","volume":"15","author":"Parthasarathy","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1038\/s41467-017-01119-w","article-title":"The \u03b220\u2013\u03b221 of gp120 is a regulatory switch for HIV-1 Env conformational transitions","volume":"8","author":"Herschhorn","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jeffy, J., Parthasarathy, D., Ahmed, S., Cervera-Benet, H., Xiong, U., Harris, M., Mazurov, D., Pickthorn, S., and Herschhorn, A. (2023). Alternative substitutions of N332 in HIV-1AD8 gp120 differentially affect envelope glycoprotein function and viral sensitivity to broadly neutralizing antibodies targeting the V3-glycan. bioRxiv, 2023.11.20.567910.","DOI":"10.1101\/2023.11.20.567910"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"100133","DOI":"10.1016\/j.xpro.2020.100133","article-title":"A Protocol for Studying HIV-1 Envelope Glycoprotein Function","volume":"1","author":"Ratnapriya","year":"2020","journal-title":"STAR Protoc."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"108432","DOI":"10.1016\/j.celrep.2020.108432","article-title":"Automated Design by Structure-Based Stabilization and Consensus Repair to Achieve Prefusion-Closed Envelope Trimers in a Wide Variety of HIV Strains","volume":"33","author":"Rawi","year":"2020","journal-title":"Cell Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1111\/febs.15814","article-title":"Adjuvant-mediated enhancement of the immune response to HIV vaccines","volume":"289","author":"Ratnapriya","year":"2022","journal-title":"FEBS J."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/11\/1161\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T05:15:18Z","timestamp":1763270118000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/11\/1161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,14]]},"references-count":54,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["vaccines13111161"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13111161","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,14]]}}}