{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:04:19Z","timestamp":1792263859656,"version":"4.4.0"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    The development of an effective HIV-1 vaccine is of paramount importance to global health. Here, we compared the influence of two adjuvants,\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    double-mutant heat-labile toxin (dmLT) and alum, on the protective immunity induced by a cyclically permuted trimeric HIV-1 envelope gp120 protein (CycP-gp120) boost. Two groups of rhesus macaques received two modified vaccinia Ankara (MVA)\/SHIV C.1086 primes followed by a CycP-gp120 protein boost adjuvanted with either dmLT (n = 9) or alum (n = 10). A group of unvaccinated macaques (n = 8) served as controls. All animals were intrarectally challenged with heterologous SHIV.CH505.375H.dCT weekly for 7 weeks. Following the challenge, dmLT-adjuvanted animals showed significant protection with a vaccine efficacy of 60.8% per exposure (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.0246). Alum-adjuvanted animals did not show significant protection (\n                    <jats:italic>p<\/jats:italic>\n                    = 0.1575). Both adjuvants induced comparable envelope-specific binding antibody in serum and rectal secretions with broad V1V2 scaffold-binding specificity. IL-6 plasma concentration correlated positively with V1V2 scaffold-binding and increased after vaccination with both adjuvants. With respect to CD4 T cells, dmLT induced higher frequencies of proliferating central memory (T\n                    <jats:sub>CM<\/jats:sub>\n                    ) and ICOS\n                    <jats:sup>+<\/jats:sup>\n                    cells in blood compared to alum. However, these proliferating CD4 T\n                    <jats:sub>CM<\/jats:sub>\n                    cells showed a decrease in the proportion of gut-homing receptor \u03b14\u03b27-expressing cells in the dmLT group compared to the alum group at week 2 post-protein boost. The V1V2 scaffold-specific IgG, proliferating T\n                    <jats:sub>CM<\/jats:sub>\n                    and ICOS\n                    <jats:sup>+<\/jats:sup>\n                    CD4 T-cell frequencies, and plasma IL-6 concentration associated positively with protection. These data demonstrate that the vaccine adjuvants dmLT and alum differentially modulate protective helper T-cell responses induced by the CycP-gp120 protein, highlighting the importance of an appropriate adjuvant for eliciting a protective immune response against HIV-1.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2025.1706958","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:35:47Z","timestamp":1768973747000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunogenicity and protection mediated by dmLT and alum adjuvants for an HIV-1 vaccine"],"prefix":"10.3389","volume":"16","author":[{"given":"Kasey","family":"Stokdyk","sequence":"first","affiliation":[{"name":"Emory National Primate Research Center, Emory University","place":["Atlanta, GA, United States"]},{"name":"Department of Microbiology and Immunology, Emory School of Medicine, Emory University","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anusmita","family":"Sahoo","sequence":"additional","affiliation":[{"name":"Emory National Primate Research Center, Emory University","place":["Atlanta, GA, United States"]},{"name":"Department of Microbiology and Immunology, Emory School of Medicine, Emory University","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sailaja","family":"Gangadhara","sequence":"additional","affiliation":[{"name":"Emory National Primate Research Center, Emory University","place":["Atlanta, GA, United States"]},{"name":"Department of Microbiology and Immunology, Emory School of Medicine, Emory University","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LaTonya D.","family":"Williams","sequence":"additional","affiliation":[{"name":"Duke Center for Human Systems Immunology, Duke University School of Medicine","place":["Durham, NC, United States"]},{"name":"Department of Surgery, Duke University Medical Center","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany M.","family":"Styles","sequence":"additional","affiliation":[{"name":"Emory National Primate Research Center, Emory University","place":["Atlanta, GA, United States"]},{"name":"Department of Microbiology and Immunology, Emory School of Medicine, Emory University","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb A.","family":"Hellman","sequence":"additional","affiliation":[{"name":"Duke Center for Human Systems Immunology, Duke University School of Medicine","place":["Durham, NC, United States"]},{"name":"Department of Surgery, Duke University Medical Center","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Duke Center for Human Systems Immunology, Duke University School of Medicine","place":["Durham, NC, United States"]},{"name":"Department of Surgery, Duke University Medical Center","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad J.","family":"Odeh","sequence":"additional","affiliation":[{"name":"Duke Center for Human Systems Immunology, Duke University School of Medicine","place":["Durham, NC, United States"]},{"name":"Department of Surgery, Duke University Medical Center","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelby","family":"Flaherty","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University Medical Center","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University Medical Center","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Arif","family":"Rahman","sequence":"additional","affiliation":[{"name":"Animal Models and Retroviral Vaccines Section, Basic Research Laboratory, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH)","place":["Bethesda, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth B.","family":"Norton","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Tulane University School of Medicine","place":["New Orleans, LA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genoveffa","family":"Franchini","sequence":"additional","affiliation":[{"name":"Animal Models and Retroviral Vaccines Section, Basic Research Laboratory, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH)","place":["Bethesda, MD, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Montefiori","sequence":"additional","affiliation":[{"name":"Department of Surgery, Duke University Medical Center","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela A.","family":"Kozlowski","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center","place":["New Orleans, LA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia D.","family":"Tomaras","sequence":"additional","affiliation":[{"name":"Duke Center for Human Systems Immunology, Duke University School of Medicine","place":["Durham, NC, United States"]},{"name":"Department of Surgery, Duke University Medical Center","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rama Rao","family":"Amara","sequence":"additional","affiliation":[{"name":"Emory National Primate Research Center, Emory University","place":["Atlanta, GA, United States"]},{"name":"Department of Microbiology and Immunology, Emory School of Medicine, Emory University","place":["Atlanta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0146387","article-title":"Exploring the potential health impact and cost-effectiveness of AIDS vaccine within a comprehensive HIV\/AIDS response in low- and middle-income countries","volume":"11","author":"Harmon","year":"2016","journal-title":"PloS One"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2014.12.006","article-title":"Insights into the trimeric HIV-1 envelope glycoprotein structure","volume":"40","author":"Ward","year":"2015","journal-title":"Trends Biochem Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00753-w","article-title":"Strategies for HIV-1 vaccines that induce broadly neutralizing antibodies","volume":"23","author":"Haynes","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"228ra38","DOI":"10.1126\/scitranslmed.3007736","article-title":"Polyfunctional Fc-effector profiles mediated by IgG subclass selection distinguish RV144 and VAX003 vaccines","volume":"6","author":"Chung","year":"2014","journal-title":"Sci Transl Med"},{"key":"B5","doi-asserted-by":"publisher","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":"B6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.10.6596","article-title":"Recombinant gp120 vaccine-induced antibodies inhibit clinical strains of HIV-1 in the presence of fc receptor-bearing effector cells and correlate inversely with HIV infection rate","volume":"178","author":"Forthal","year":"2007","journal-title":"J Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803115","article-title":"Contribution of non-neutralizing vaccine-elicited antibody activities to improved protective efficacy in rhesus macaques immunized with Tat\/Env compared to multigenic vaccines","volume":"182","author":"Florese","year":"2009","journal-title":"J Immunol (Baltimore Md: 1950)"},{"key":"B8","doi-asserted-by":"publisher","first-page":"310rv7","DOI":"10.1126\/scitranslmed.aac7732","article-title":"Immune correlates of vaccine protection against HIV-1 acquisition","volume":"7","author":"Corey","year":"2015","journal-title":"Sci Transl Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113425","article-title":"Immune-correlates analysis of an HIV-1 vaccine efficacy trial","volume":"366","author":"Haynes","year":"2012","journal-title":"New Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abl4102","article-title":"A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques","volume":"7","author":"Sahoo","year":"2022","journal-title":"Sci Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-023-01353-7","article-title":"Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques","volume":"8","author":"Rahman","year":"2023","journal-title":"Nat Microbiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2010.12.016","article-title":"A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples","volume":"366","author":"Ackerman","year":"2011","journal-title":"J Immunol Methods"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aat7796","article-title":"Antigen-specific antibody Fc glycosylation enhances humoral immunity via the recruitment of complement","volume":"3","author":"Lofano","year":"2018","journal-title":"Sci Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"108502","DOI":"10.1016\/j.celrep.2020.108502","article-title":"HIV antibody Fc N-linked glycosylation is associated with viral rebound","volume":"33","author":"Offersen","year":"2020","journal-title":"Cell Rep"},{"key":"B15","doi-asserted-by":"publisher","first-page":"228ra39","DOI":"10.1126\/scitranslmed.3007730","article-title":"Vaccine-induced Env V1-V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination","volume":"6","author":"Yates","year":"2014","journal-title":"Sci Transl Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908492","article-title":"Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand","volume":"361","author":"Rerks-Ngarm","year":"2009","journal-title":"New Engl J Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0087572","article-title":"Vaccine-induced IgG antibodies to V1V2 regions of multiple HIV-1 subtypes correlate with decreased risk of HIV-1 infection","volume":"9","author":"Zolla-Pazner","year":"2014","journal-title":"PloS One"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/COH.0000000000000551","article-title":"Vaccine-induced V1V2-specific antibodies control and or protect against infection with HIV, SIV and SHIV","volume":"14","author":"Zolla-Pazner","year":"2019","journal-title":"Curr Opin HIV AIDS"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4105","article-title":"Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition","volume":"22","author":"Vaccari","year":"2016","journal-title":"Nat Med"},{"key":"B20","doi-asserted-by":"publisher","first-page":"102047","DOI":"10.1016\/j.isci.2021.102047","article-title":"Anti-V2 antibodies virus vulnerability revealed by envelope V1 deletion in HIV vaccine candidates","volume":"24","author":"Silva de Castro","year":"2021","journal-title":"iScience"},{"key":"B21","doi-asserted-by":"publisher","first-page":"9102","DOI":"10.1038\/s41467-024-53359-2","article-title":"Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response","volume":"15","author":"Rahman","year":"2024","journal-title":"Nat Commun"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0274-9","article-title":"CD8+ T cells in HIV control, cure and prevention","volume":"20","author":"Collins","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aav1800","article-title":"Strong T(H)1-biased CD4 T cell responses are associated with diminished SIV vaccine efficacy","volume":"11","author":"Chamcha","year":"2019","journal-title":"Sci Transl Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1407466112","article-title":"Activated CD4+CCR5+ T cells in the rectum predict increased SIV acquisition in SIVGag\/Tat-vaccinated rhesus macaques","volume":"112","author":"Carnathan","year":"2015","journal-title":"Proc Natl Acad Sci"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00163-y","article-title":"Emerging concepts in the science of vaccine adjuvants","volume":"20","author":"Pulendran B","year":"2021","journal-title":"Nat Rev Drug Discov"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1021\/bi300003v","article-title":"Designed cyclic permutants of HIV-1 gp120: implications for envelope trimer structure and immunogen design","volume":"51","author":"Saha","year":"2012","journal-title":"Biochemistry"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.725614","article-title":"Structure-based design of cyclically permuted HIV-1 gp120 trimers that elicit neutralizing antibodies","volume":"292","author":"Kesavardhana","year":"2017","journal-title":"J Biol Chem"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01796-17","article-title":"A Trimeric HIV-1 Envelope gp120 Immunogen Induces Potent and Broad Anti-V1V2 Loop Antibodies against HIV-1 in Rabbits and Rhesus Macaques","volume":"92","author":"Jones","year":"2018","journal-title":"J Virol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1038\/s41467-019-08739-4","article-title":"HIV-1 vaccination by needle-free oral injection induces strong mucosal immunity and protects against SHIV challenge","volume":"10","author":"Jones","year":"2019","journal-title":"Nat Commun"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00538-10","article-title":"Characterization of a mutant Escherichia coli heat-labile toxin, LT(R192G\/L211A), as a safe and effective oral adjuvant","volume":"18","author":"Norton","year":"2011","journal-title":"Clin Vaccine Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1128\/mSphere.00215-18","article-title":"The mucosal vaccine adjuvant LT(R192G\/L211A) or dmLT","volume":"3","author":"Clements","year":"2018","journal-title":"mSphere"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2023.102398","article-title":"Recent advances in enterotoxin vaccine adjuvants","volume":"85","author":"Crothers","year":"2023","journal-title":"Curr Opin Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.038943-0","article-title":"Alum adjuvant: some of the tricks of the oldest adjuvant","volume":"61","author":"Kool","year":"2012","journal-title":"J Med Microbiol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00943","article-title":"Different adjuvants induce common innate pathways that are associated with enhanced adaptive responses against a model antigen in humans","volume":"8","author":"Burny","year":"2017","journal-title":"Front Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1128\/iai.72.11.6519-6527.2004","article-title":"Phase I testing of a malaria vaccine composed of hepatitis B virus core particles expressing plasmodium falciparum circumsporozoite epitopes","volume":"72","author":"Nardin","year":"2004","journal-title":"Infection Immun"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1089\/aid.1995.11.1479","article-title":"Safety and immunogenicity of a recombinant HIV type 1 glycoprotein 160 boosted by a V3 synthetic peptide in HIV-negative volunteers","volume":"11","author":"Salmon-C\u00e9ron","year":"1995","journal-title":"AIDS Res Hum Retroviruses"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1038\/nri2510","article-title":"Towards an understanding of the adjuvant action of aluminium","volume":"9","author":"Marrack","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiq105","article-title":"Phase 1 safety and immunogenicity testing of DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles","volume":"203","author":"Goepfert","year":"2011","journal-title":"J Infect Dis"},{"key":"B39","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1093\/infdis\/jiu003","article-title":"Specificity and 6-month durability of immune responses induced by DNA and recombinant modified vaccinia Ankara vaccines expressing HIV-1 virus-like particles","volume":"210","author":"Goepfert","year":"2014","journal-title":"J Infect Dis"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2016.03.002","article-title":"A new cell line for high throughput HIV-specific antibody-dependent cellular cytotoxicity (ADCC) and cell-to-cell virus transmission studies","volume":"433","author":"Orlandi","year":"2016","journal-title":"J Immunol Methods"},{"key":"B41","doi-asserted-by":"publisher","first-page":"4789","DOI":"10.1038\/s41467-023-40430-7","article-title":"Intradermal but not intramuscular modified vaccinia Ankara immunizations protect against intravaginal tier2 simian-human immunodeficiency virus challenges in female macaques","volume":"14","author":"Bollimpelli","year":"2023","journal-title":"Nat Commun"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.02.066","article-title":"Vaccine-elicited SIV and HIV envelope-specific IgA and IgG memory B cells in rhesus macaque peripheral blood correlate with functional antibody responses and reduced viremia","volume":"29","author":"Brocca-Cofano","year":"2011","journal-title":"Vaccine"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01687-18","article-title":"Early T follicular helper cell responses and germinal center reactions are associated with viremia control in immunized rhesus macaques","volume":"93","author":"Hait","year":"2018","journal-title":"J Virol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017739","article-title":"IL-21 and IL-6 are critical for different aspects of B cell immunity and redundantly induce optimal follicular helper CD4 T cell (Tfh) differentiation","volume":"6","author":"Eto","year":"2011","journal-title":"PloS One"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2947","article-title":"The cytokine TGF-\u03b2 co-opts signaling via STAT3-STAT4 to promote the differentiation of human TFH cells","volume":"15","author":"Schmitt","year":"2014","journal-title":"Nat Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-07-230631","article-title":"IL-6 increases B-cell IgG production in a feed-forward proinflammatory mechanism to skew hematopoiesis and elevate myeloid production","volume":"115","author":"Maeda","year":"2010","journal-title":"Blood"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiad327","article-title":"Geographic and population distributions of human immunodeficiency virus (HIV)\u20131 and HIV-2 circulating subtypes: A systematic literature review and meta-analysis (2010\u20132021)","volume":"228","author":"Williams","year":"2023","journal-title":"J Infect Dis"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa497","article-title":"Preferential infection of \u03b14\u03b27+ Memory CD4+ T cells during early acute human immunodeficiency virus type 1 infection","volume":"71","author":"Tokarev","year":"2020","journal-title":"Clin Infect Dis"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aam6354","article-title":"Integrin \u03b14\u03b27 expression on peripheral blood CD4+ T cells predicts HIV acquisition and disease progression outcomes","volume":"10","author":"Sivro","year":"2018","journal-title":"Sci Trans Med"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0684.2009.00372.x","article-title":"CD4 T cell subsets in the mucosa are CD28+Ki-67\u2013HLA-DR\u2013CD69+ but show differential infection based on \u03b14\u03b27 receptor expression during acute SIV infection","volume":"38","author":"Kader","year":"2009","journal-title":"J Med Primatol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2009.90","article-title":"\u03b14+\u03b27hiCD4+ memory T cells harbor most Th-17 cells and are preferentially infected during acute SIV infection","volume":"2","author":"Kader","year":"2009","journal-title":"Mucosal Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1172\/JCI187992","article-title":"NK cell activation and CD4+ T cell \u03b14\u03b27 expression are associated with susceptibility to HIV-1","volume":"135","author":"Machmach","year":"2025","journal-title":"J Clin Invest"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01012.x","article-title":"Molecular mechanisms of T-cell tolerance","volume":"241","author":"Nurieva","year":"2011","journal-title":"Immunol Rev"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051718","article-title":"The adjuvant double mutant Escherichia coli heat labile toxin enhances IL-17A production in human T cells specific for bacterial vaccine antigens","volume":"7","author":"Leach","year":"2012","journal-title":"PloS One"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401633","article-title":"Cholera Toxin, and the Related Nontoxic Adjuvants mmCT and dmLT, Promote Human Th17 Responses via Cyclic AMP\u2013Protein Kinase A and Inflammasome-Dependent IL-1 Signaling","volume":"194","author":"Larena","year":"2015","journal-title":"J Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.030","article-title":"Microbiota-dependent sequelae of acute infection compromise tissue-specific immunity","volume":"163","author":"Morais da Fonseca","year":"2015","journal-title":"Cell"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0224073","article-title":"Evaluation of the reactogenicity, adjuvanticity and antigenicity of LT(R192G) and LT(R192G\/L211A) by intradermal immunization in mice","volume":"14","author":"Maciel","year":"2019","journal-title":"PloS One"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2200221","article-title":"The adjuvant combination of dmLT and monophosphoryl lipid A activates the canonical, nonpyroptotic NLRP3 inflammasome in dendritic cells and significantly interacts to expand antigen-specific CD4 T cells","volume":"210","author":"Bauer","year":"2023","journal-title":"J Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.12.053","article-title":"Intradermal vaccination with a Pseudomonas aeruginosa vaccine adjuvanted with a mutant bacterial ADP-ribosylating enterotoxin protects against acute pneumonia","volume":"37","author":"Baker","year":"2019","journal-title":"Vaccine"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0227047","article-title":"LTA1 and dmLT enterotoxin-based proteins activate antigen-presenting cells independent of PKA and despite distinct cell entry mechanisms","volume":"15","author":"Valli","year":"2020","journal-title":"PloS One"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003789","article-title":"Escherichia coli Heat-Labile Enterotoxin Promotes Protective Th17 Responses against Infection by Driving Innate IL-1 and IL-23 Production","volume":"186","author":"Brereton","year":"2011","journal-title":"J Immunol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1126\/science.1135299","article-title":"Adjuvant-enhanced antibody responses occur without Toll-like receptor signaling","volume":"314","author":"Gavin","year":"2006","journal-title":"Sci (New York NY)"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201041126","article-title":"Selective effects of NF-\u03baB1 deficiency in CD4+ T cells on Th2 and TFh induction by alum-precipitated protein vaccines","volume":"41","author":"Serre","year":"2011","journal-title":"Eur J Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.1.17","article-title":"Cutting edge: inflammasome activation by alum and alum\u2019s adjuvant effect are mediated by NLRP3","volume":"181","author":"Li","year":"2008","journal-title":"J Immunol"},{"key":"B65","doi-asserted-by":"crossref","DOI":"10.1002\/eji.200838549","article-title":"The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity","volume":"38","author":"Franchi","year":"2008","journal-title":"Eur J Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.6.3755","article-title":"Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome","volume":"181","author":"Kool","year":"2008","journal-title":"J Immunol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/nature06939","article-title":"Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants","volume":"453","author":"Eisenbarth","year":"2008","journal-title":"Nature"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900164","article-title":"Alum induces innate immune responses through macrophage and mast cell sensors, but these sensors are not required for alum to act as an adjuvant for specific immunity","volume":"183","author":"McKee","year":"2009","journal-title":"J Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200323801","article-title":"The IL-1 receptor\u20041 is critical for Th2 cell type airway immune responses in a mild but not in a more severe asthma model","volume":"33","author":"Schmitz","year":"2003","journal-title":"Eur J Immunol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-275529","article-title":"Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo","volume":"116","author":"Munks","year":"2010","journal-title":"Blood"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.015","article-title":"An unexpected role for uric acid as an inducer of T helper 2 cell immunity to inhaled antigens and inflammatory mediator of allergic asthma","volume":"34","author":"Kool","year":"2011","journal-title":"Immunity"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2403","article-title":"DNA released from dying host cells mediates aluminum adjuvant activity","volume":"17","author":"Marichal","year":"2011","journal-title":"Nat Med"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.11.032","article-title":"Restricted clonality and limited germinal center reentry characterize memory B cell reactivation by boosting","volume":"180","author":"Mesin","year":"2020","journal-title":"Cell"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2025.102369","article-title":"Chimeric hemagglutinin-based universal influenza mRNA vaccine induces protective immunity and bone marrow plasma cells in rhesus macaques","volume":"102369","author":"Styles","year":"2025","journal-title":"Cell Rep Med"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1002\/path.1700280217","article-title":"The antigenic effect of intravenous injection of diphtheria toxin","volume":"28","author":"Glenny","year":"1925","journal-title":"J Pathol Bacteriol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1002\/path.1700340214","article-title":"Rate of Disappearance of Diphtheria Toxoid injected into Rabbits and Guinea pigs: Toxoid precipitated with Alum","volume":"34","author":"Glenny","year":"1931","journal-title":"J Pathol Bacteriol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0753-3","article-title":"Engineered immunogen binding to alum adjuvant enhances humoral immunity","volume":"26","author":"Moyer","year":"2020","journal-title":"Nat Med"},{"key":"B78","doi-asserted-by":"publisher","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":"B79","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600320","article-title":"Cytokine-independent detection of antigen-specific germinal center T follicular helper cells in immunized nonhuman primates using a live cell activation-induced marker technique","volume":"197","author":"Havenar-Daughton","year":"2016","journal-title":"J Immunol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.06.019","article-title":"Controlling timing and location in vaccines","volume":"158","author":"Irvine","year":"2020","journal-title":"Advanced Drug Delivery Rev"},{"key":"B81","doi-asserted-by":"publisher","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 U States America"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1004360","article-title":"Safety and immunogenicity of a subtype C ALVAC-HIV (vCP2438) vaccine prime plus bivalent subtype C gp120 vaccine boost adjuvanted with MF59 or alum in healthy adults without HIV (HVTN 107): A phase 1\/2a randomized trial","volume":"21","author":"Moodie","year":"2024","journal-title":"PloS Med"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1606636113","article-title":"Envelope residue 375 substitutions in simian\u2013human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques","volume":"113","author":"Li","year":"2016","journal-title":"Proc Natl Acad Sci"},{"key":"B84","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1126\/science.292.5514.69","article-title":"Control of a mucosal challenge and prevention of AIDS by a multiprotein DNA\/MVA vaccine","volume":"292","author":"Amara","year":"2001","journal-title":"Science"},{"key":"B85","doi-asserted-by":"publisher","first-page":"914969","DOI":"10.3389\/fimmu.2022.914969","article-title":"Frontiers | V2 hotspot optimized MVA vaccine expressing stabilized HIV-1 Clade C envelope Gp140 delays acquisition of heterologous Clade C Tier 2 challenges in Mamu-A*01 negative Rhesus Macaques","volume":"13","author":"Styles","year":"2022","journal-title":"Front Immunol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110436","article-title":"Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies","volume":"38","author":"Sahoo","year":"2022","journal-title":"Cell Rep"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01843-17","article-title":"HIV-1 envelope glycoproteins from diverse clades differentiate antibody responses and durability among vaccinees","volume":"92","author":"Yates","year":"2018","journal-title":"J Virol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105320","article-title":"Immune correlates analysis of the Imbokodo (HVTN 705\/HPX2008) efficacy trial of a mosaic HIV-1 vaccine regimen evaluated in Southern African people assigned female sex at birth: a two-phase case-control study","volume":"108","author":"Kenny","year":"2024","journal-title":"EBioMedicine"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-021-00305-8","article-title":"Meta-analysis of HIV-1 vaccine elicited mucosal antibodies in humans","volume":"6","author":"Seaton","year":"2021","journal-title":"NPJ Vaccines"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1215393110","article-title":"DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge","volume":"110","author":"Patel","year":"2013","journal-title":"Proc Natl Acad Sci"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-170-3_26","article-title":"Measuring HIV neutralization in a luciferase reporter gene assay","volume":"485","author":"Montefiori","year":"2009","journal-title":"Methods Mol Biol"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.79.16.10108-10125.2005","article-title":"Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies","volume":"79","author":"Li","year":"2005","journal-title":"J Virol"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600629","article-title":"High doses of GM-CSF inhibit antibody responses in rectal secretions and diminish modified vaccinia ankara\/simian immunodeficiency virus vaccine protection in TRIM5alpha-restrictive macaques","volume":"197","author":"Kannanganat","year":"2016","journal-title":"J Immunol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005817","article-title":"Antibody-mediated internalization of infectious HIV-1 virions differs among antibody isotypes and subclasses","volume":"12","author":"Tay","year":"2016","journal-title":"PloS Pathog"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1706958\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T07:39:41Z","timestamp":1771918781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1706958\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":94,"alternative-id":["10.3389\/fimmu.2025.1706958"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1706958","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"article-number":"1706958"}}