Current HIV Research最新文献

{"title":"Current HIV Research Thematic Issue on \"HIV Vaccine Development\".","authors":"John P Moore","doi":"10.2174/011570162X450381251027072501","DOIUrl":"https://doi.org/10.2174/011570162X450381251027072501","url":null,"abstract":"","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":"23 6","pages":"351-352"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Rising Impact of HPV Infection in the Antiretroviral Therapy (ART) Era.","authors":"Elia Asensi-Diaz, Irene Carrillo, Aws Al-Hayani, Maria Mejias-Ledesma, Hector Guadalajara, Ignacio Azinovic, Jose Luis Dominguez Trsitancho, Llanos Salar Vidal, Víctor Castellano, Damian Garcia-Olmo, Miguel Górgolas, Alfonso Cabello-Ubeda","doi":"10.2174/011570162X381694250925045507","DOIUrl":"10.2174/011570162X381694250925045507","url":null,"abstract":"<p><strong>Introduction: </strong>Since the introduction of antiretroviral therapy (ART), non-AIDS malignancies- particularly anal cancer-have increased in people living with HIV (PLHIV). However, associated risk factors and disease progression remain poorly defined.</p><p><strong>Material and methods: </strong>This retrospective observational study analysed PLHIV who developed anal cancer between 2000 and 2021 at a third-level university hospital. Epidemiological, immunological, and microbiological factors, as well as disease management and outcomes, were assessed.</p><p><strong>Results: </strong>A total of 38 patients were included, 95% of whom were men, with an incidence rate of 105 cases per 100,000 person-years. The median CD4 nadir was 169 cells/μl, with 60% of patients having a CD4 nadir <200 cells/μl, and 93.3% had a CD4/CD8 ratio <0.4. HPV infection was documented in 100% of tested patients (35/38), and 50% presented with advanced tumor stages. At 2 years post-diagnosis, 66% achieved complete remission, while 13.2% had a recurrence. Long-term tumor-related mortality was 15%, with an overall survival of 66%.</p><p><strong>Discussion: </strong>A significant number of patients presented with advanced-stage anal cancer and ongoing immunosuppression, emphasising the need for earlier detection and better follow-up. Despite guidelines, screening participation remains low, highlighting the importance of multidisciplinary care and targeted prevention strategies in high-risk PLHIV populations. However, as a retrospective single-centre study with a limited sample size, our findings may be affected by information and selection bias, restricting broader applicability.</p><p><strong>Conclusion: </strong>Co-infection with HIV and HPV and low CD4 nadir were common features in these patients. HPV prevention and anal dysplasia screening are crucial to reducing this emerging condition.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":"43-49"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The RV144 Trial Might Still Yield Useful Information.","authors":"John P Moore","doi":"10.2174/011570162X355671250402083527","DOIUrl":"10.2174/011570162X355671250402083527","url":null,"abstract":"<p><p>This article discusses how the RV144 Phase 3 HIV-1 vaccine trial conducted over 15 years ago impacted the subsequent direction of research intended to create and evaluate vaccines with potentially greater efficacy. Follow-on Phase 2b and Phase 3 trials directly or indirectly inspired by the modest efficacy reported for the RV144 trial have not shown any significant protection against HIV-1 acquisition. No credibly protective new immunogens have emerged from the Correlates of Protection (CoP) or Risk (CoR) analyses conducted after RV144-inspired studies in either humans or various macaque models. Notably, the RV144 trial did not induce neutralizing antibodies (NAbs), only non-NAbs. However, only NAbs have been shown to be protective in macaque models. One possible but underappreciated explanation for the outcome of the RV144 trial could be trained innate immune responses against the non-HIV-1 canarypox virus vector antigens, considering the placebo group only received saline. In this article, the author outlines how monkey model research based directly or indirectly on the RV144 trial could still yield useful information on the possible role of trained immunity in short-term vaccine protection. However, non-human primate research, in general, should now focus on testing new immunogens that have a reasonable chance of inducing NAbs in humans, rather than expending more resources on CoP/CoR studies inspired by the RV144 trial and its follow-ups.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":"357-362"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Changing Face of HIV-Associated Malignancies: Is this the Same in Turkey As Well?","authors":"Yıldız Olcar, Alper Gunduz, Dilek Yıldız Sevgi, İlyas Dokmetas","doi":"10.2174/011570162X392859251119055734","DOIUrl":"10.2174/011570162X392859251119055734","url":null,"abstract":"<p><strong>Introduction: </strong>Cancers remain a major cause of mortality among individuals with HIV infection. This study aimed to determine the incidence, prevalence, and mortality of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) in people living with HIV (PLWH).</p><p><strong>Methods: </strong>This retrospective, cross-sectional study was conducted in Istanbul. Among patients diagnosed with HIV/AIDS between January 2011 and December 2019, those who developed cancer were analyzed. To assess changes in cancer types over time, the study period was divided into three-year intervals.</p><p><strong>Results: </strong>Cancer was diagnosed in 57 (3.9%) of the 1,438 patients. The mean CD4 count was 272.3/mm³. Patients in the cancer group had significantly higher mean age at HIV diagnosis, higher HIV RNA levels, and lower CD4+ T lymphocyte counts. A notably high rate (72%) of simultaneous diagnosis of cancer and HIV was observed in the ADCs group. Kaposi sarcoma was identified in 23 (71.8%) patients, and non-Hodgkin lymphoma (NHL) in 9 patients. Hodgkin lymphoma and lung cancer were the most common cancers in the NADCs group.</p><p><strong>Discussion: </strong>People living with HIV are experiencing longer life expectancy due to ART; however, this also increases cancer risk, emphasizing the need for national screening guidelines that consider age, gender, and immune status. A multidisciplinary approach is essential for effective prevention and treatment strategies. Since cancer risk is multifactorial, larger prospective and multicenter studies are needed to strengthen and expand these findings.</p><p><strong>Conclusions: </strong>These findings highlight that AIDS-defining cancers continue to be a significant clinical concern in Turkey. Cancer screening should be integrated both at the time of HIV diagnosis and during routine follow-up of PLWH.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":"157-167"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis and Dysfunction of CD3⁺CD4^-CD8^- T Cells are Associated with Poor Immune Reconstitution in HIV Patients.","authors":"Xi Quan, Qing Xiao, Junli Luo, Chaoyu Wang, Yixing Zhou, Chensi Zeng, Xiaomei Zhang, Jieping Li, Dehong Huang, Chongling Hu, Bingling Guo, Shuang Chen, Zailin Yang, Xiaohong Deng, Yao Liu","doi":"10.2174/011570162X366300250509112302","DOIUrl":"10.2174/011570162X366300250509112302","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Some HIV patients stay in an immune unresponsive state after antiretroviral therapy (ART), with a notably higher risk of AIDS-related and non-AIDS-related complications. Double-negative T cells (DNT) can compensate for immunity and prevent immune overactivation in HIV patients. Also, immune non-responders (INRs) have fewer DNT cells than immune responders (IRs). HIV infection and ART can change the dynamic function of cell mitochondria, which are crucial in ferroptosis. Ferroptosis is a form of cell death marked by the accumulation of reactive oxygen species (ROS) and iron-dependent lipid peroxidation. Yet, the changes in DNT cell function in INRs and the impact of ferroptosis on immune reconstitution remain unclear.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;Our study focused on the expression level of DNT cells in HIV immune non-responders. Then, we detected markers of ferroptosis, cell activation, proliferation, killing function, and inflammatory states of DNT cells in INRs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The study involved 88 PLHIVs who had received antiretroviral therapy for over 4 years and tested virus-negative. These patients were classified into two groups: 28 INRs (CD4 &lt; 350/μl) and 60 IRs (CD4 ≥350/μl). Additionally, 25 sex- and age-matched HCs were included. Flow cytometry was used to detect ferroptosis markers (JC-1, Lipid ROS, lipid peroxidation), cell proliferation, and cell activation. Transmission electron microscopy (TEM) was applied to observe mitochondrial morphology. Finally, statistical analysis was performed on the detection results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;After long-term antiretroviral therapy, we found that INRs had a lower DNT cell count than IRs. Regarding proliferation and activation, our results showed higher CD38/HLA-DR co-expression and Ki67 expression in INRs' DNT cells than in IRs', indicating over-activation of DNT cells in INRs. In terms of killing function, the perforin and granzyme B levels in INRs' DNT cells were lower than those in IRs', suggesting impaired killing function of DNT cells in INRs. For ferroptosis, the proportion of DNT cells with decreased MMP in INRs was higher than in IRs and HCs. INRs' DNT cells also had higher levels of lipid ROS and lipid peroxidation compared to those in IRs and HCs. TEM revealed that the mitochondria of INRs' DNT cells had typical morphological features. Moreover, INRs' DNT cells had a greater degree of inflammation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our study centered on the proliferation, activation, ferroptosis, killing function, and inflammatory status of DNT cells in INRs. We found that DNT cells in INRs had more active proliferation and activation, weakened killing function, mitochondrial function with typical ferroptosis features, and increased TNF-αlevels. Correlation analysis indicated that DNT cell overactivation (Ki-67+, CD38+HLA-DR+), MMP reduction ratio, and TNF-αexpression were negatively related to immune reconstitution in P","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":"50-61"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Impact of HIV-1 Tat on FDFT1 Suppression, Changes in Cholesterol Level, and KSHV Replication in BCBL1 Cells.","authors":"Qiaozhen Liu, Xiaoying Chen, Dewen Liu, Yuting Zou, Weiling Yang, Ziyi Cao, Yao Ding, Weihang Ji, Na Xiao, Huaying Tang, Yan Jiang, Liandeng Wei, Yi Zeng","doi":"10.2174/1570162X24999260319143852","DOIUrl":"https://doi.org/10.2174/1570162X24999260319143852","url":null,"abstract":"<p><p>In the published version of this article [1], the author identified the error in the reported funding grant number. This has now been corrected. The original article can be found online at: https://www.eurekaselect.com/article/150528ss Details of the error and a correction are provided here. ORIGINAL: FUNDING This research was financially supported by the National Natural Science Foundation of China (grant number: 321600034), the Guangxi Natural Science Foundation of China (grant number: 2021GXNSFAA075026), and the Baise Science and Technology project of Guangxi, China (grant numbers: 20212346 and 20224146). CORRECTED: FUNDING This research was financially supported by the National Natural Science Foundation of China (grant number: 32160034), the Guangxi Natural Science Foundation of China (grant number: 2021GXNSFAA075026), and the Baise Science and Technology project of Guangxi, China (grant numbers: 20212346 and 20224146). The authors apologize for any inconvenience caused.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":"24 1","pages":"74"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148344123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Germline Targeting Vaccine Concept: Overview and Updates from HIV Pre-Clinical and Clinical Trials.","authors":"Leonidas Stamatatos","doi":"10.2174/011570162X358302250206074255","DOIUrl":"10.2174/011570162X358302250206074255","url":null,"abstract":"<p><p>An effective HIV-1 vaccine should elicit diverse immune responses, including broadly neutralizing antibodies (bNAbs). Such antibodies recognize regions of the viral envelope glycoprotein (Env) that are conserved among the diverse HIV-1 clades and strains. They are isolated from people living with HIV-1 to protect animals from experimental viral exposure and reduce HIV-1 acquisition in clinical settings. However, despite efforts spanning several decades, bNAbs have not been elicited through immunization. The HIV Env efficiently binds bNAbs, but not their unmutated (germline, gl) precursors. In contrast, Env readily engages the germline precursors of antibodies with no, or very narrow, cross-neutralizing activities (non-neutralizing antibodies, nnAbs). That, in part, explains why Env-based immunogens consistently elicit nnAbs, but not bNAbs. In the past decade, Env-derived proteins have been specifically designed to engage the germline precursors of diverse bNAbs. These 'germline-targeting' Env immunogens activate the corresponding naive B cells in vivo, but are unable to guide their proper maturation towards their broadly neutralizing forms. For this, immunizations with currently not well-defined heterologous Envs are required. Here, we discuss the development of germline-targeting Env immunogens, their in vivo evaluation, and the strategies currently under evaluation that aim to rapidly guide the maturation of germline-precursor BCRs into their broadly neutralizing forms.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":"380-390"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13223421/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Characteristics of Peripheral Blood Lymphocyte Subsets in HIV-related Diffuse Large B-cell Lymphoma Patients and Their Impact on Treatment Efficacy.","authors":"Huiyu Xiang, Can Lin, Shuang Chen, Yu Peng, Tingting Jiang, Changhai Lin, Qing Xiao, Xiaomei Zhang, Tingting Liu, Nanjun Li, Xinyi Tang, Yakun Zhang, Junxi Liu, Zailin Yang","doi":"10.2174/011570162X369231250818043532","DOIUrl":"10.2174/011570162X369231250818043532","url":null,"abstract":"<p><strong>Introduction: </strong>Peripheral blood lymphocyte subsets have been shown to influence prognosis in HIV-associated Diffuse Large B-Cell Lymphoma (HIV-DLBCL), a rare and highly aggressive form of non-Hodgkin's lymphoma linked to immunosuppression and abnormal B-cell proliferation. To lay the foundation for individualized therapy based on factors such as CD4+/CD8+ ratio and Treg/NK cell characteristics, this retrospective study was conducted to explore the variations in lymphocyte subset levels.</p><p><strong>Methods: </strong>Overall, 51 HIV-DLBCL patients, 50 DLBCL patients, and 42 Healthy Donors (HD) were enrolled in the study. Data were extracted from outpatient records and the Hospital Information Management System. SPSS 27.0 software was used for statistical analysis of the data.</p><p><strong>Results: </strong>Significant differences in lymphocyte subsets were observed between groups. HIVDLBCL patients showed decreased CD4⁺ T cell and regulatory T cell (Treg) counts/percentages compared to DLBCL patients and HD, but increased CD8⁺ T cell counts and percentages, as well as Treg percentages. Age-stratified analysis revealed that older HIV-DLBCL patients had lower CD8⁺ T cell counts, reduced CD3⁺ T cell percentages, and elevated CD56⁺CD16⁺ NK cell proportions compared to their younger counterparts.</p><p><strong>Discussion: </strong>This study revealed a distinct pattern of immune dysregulation in HIV-DLBCL patients, characterized by CD4⁺ T cell depletion and CD8⁺ T cell expansion, which is consistent with previous studies. Age-related immunosenescence may exacerbate the increased proportion of NK cells and the decline in T-cell function, suggesting a poorer prognosis in elderly patients. However, the lack of association between lymphocyte subsets and chemotherapy efficacy may reflect the broad impact of standard regimens on immune reconstitution. Limitations include the small sample size, absence of functional experiments, and failure to assess the influence of coinfections. Future studies should expand the cohort and integrate multi-omics data to validate these findings.</p><p><strong>Conclusion: </strong>Patients with HIV-DLBCL have distinctive alterations in peripheral blood lymphocyte subsets, such as a decreased absolute count and percentage of CD4+ T cells, in comparison to individuals with DLBCL. These alterations appear age-related and showed no significant association with prior antiretroviral therapy. The therapeutic effect of chemotherapy for HIV-DLBCL, however, might not be impacted by the low absolute count and percentage of CD4+ T-cells in peripheral blood, as well as whether or not they had previously received antiretroviral therapy.these findings.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":"62-73"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13555762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of Preclinical and Clinical Vaccine Safety and Immunogenicity Testing for Development of a Pediatric HIV Vaccine to Achieve Protective HIV Immunity Prior to Adolescence.","authors":"Genevieve G Fouda, Anjali Singh, Ashley Nelson, Holly Janes, Troy Martin, Ofer Levy, Di Wu, Fei Zou, Patrick Jean-Philippe, Kristina De Paris, Koen K A Van Rompay, Sallie R Permar","doi":"10.2174/011570162X366522250721113420","DOIUrl":"10.2174/011570162X366522250721113420","url":null,"abstract":"<p><p>An optimal HIV vaccine should provide protective immunity before sexual debut to prevent infection in adolescents and young adults, including acute infections in women of childbearing age. Such a vaccine will likely require multiple sequential immunization doses and would therefore be ideally initiated in childhood. Many of the world's most successful vaccines are initiated in childhood for the induction of lifelong immunity and/or immunity that can be boosted later in life as part of the WHO Expanded Program on Immunization (EPI). Thus, the EPI vaccine framework provides an infrastructure that could be leveraged for the implementation of a multidose HIV immunization regimen. Early childhood also provides a window of time in which there isminimal HIV exposure risk, and the plasticity of the early life immune landscapemay present advantages for the elicitation of broadly neutralizing Antibodies (bnAbs), a primary target for HIV vaccination. Sequential vaccination with adjuvanted immunogens targeting specific bnAb lineages is a promising HIV vaccine strategy, and several vaccine candidates are currently being tested in adult clinical trials. It will be critical to evaluate the most promising immunogens and adjuvants in pediatric settings. Preclinical studies, including in vitro and in silico modelling as well as studies in animal models, will be essential to guide the design of future pediatric vaccine trials. This review summarizes current advances in bnAb germline targeting immunization. It provides the rationale for a better integration of preclinical and clinical vaccine studies to facilitate the development of a vaccine that achieves protective immunity in preadolescence.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":"510-524"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13067288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling an Immunological Mystery: Deciphering the Durability Divide in Vaccine-Elicited Antibody Responses.","authors":"George K Lewis, Stanca Ciupe, Mohammad Sajadi","doi":"10.2174/011570162X366336250707084941","DOIUrl":"10.2174/011570162X366336250707084941","url":null,"abstract":"<p><p>Achieving durable antibody-mediated protection remains critical in vaccine development, particularly for viral diseases like COVID-19 and HIV. We discuss factors influencing antibody durability, highlighting the role of long-lived plasma cells (LLPCs) in the bone marrow, which are essential for sustained antibody production over many years. The frequencies and properties of bone marrow LLPC are critical determinants of the broad spectrum of antibody durability for different vaccines. Vaccines for diseases like measles and mumps elicit long-lasting antibodies; those for COVID-19 and HIV do not. High epitope densities in the vaccine are known to favor antibody durability, but we discuss three underappreciated variables that also play a role in long-lived antibody responses. First, in addition to high epitope densities, we discuss the importance of CD21 as a critical determinant of antibody durability. CD21 is a B cell antigen receptor (BCR) complex component. It significantly affects BCR signaling strength in a way essential for generating LLPC in the bone marrow. Second, all antibody-secreting cells (ASC) are not created equal. There is a four-log range of antibody secretion rates, and we propose epigenetic imprinting of different rates on ASC, including LLPC, as a factor in antibody durability. Third, antibody durability afforded by bone marrow LLPC is independent of continuous antigenic stimulation. By contrast, tissue-resident T-bet+CD21low ASC also persists in secondary lymphoid tissues and continuously produces antibodies depending on persisting antigen and the tissue microenvironment. We discuss these variables in the context of making an HIV vaccine that elicits broadly neutralizing antibodies against HIV that persist at protective levels without continuous vaccination over many years.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":"494-509"},"PeriodicalIF":0.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}