Vaccines最新文献

{"title":"Inactivation of Zika Virus with Hydroxypropyl-Beta-Cyclodextrin.","authors":"Cory R Hewitt, Nicholas J Wixon, Arthur Gallegos, You Zhou, Victor C Huber, M Scott Killian","doi":"10.3390/vaccines13010079","DOIUrl":"10.3390/vaccines13010079","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Zika virus (ZIKV) infection is associated with life-threatening diseases in humans. To date, there are no available FDA-approved therapies or vaccines for the specific treatment or prevention of ZIKV infection. Variation in the ZIKV envelope protein (Env), along with its complex quaternary structure, presents challenges to synthetic approaches for developing an effective vaccine and broadly neutralizing antibodies (bnAbs). We hypothesized that beta-cyclodextrin (BCD) could be used to uniquely inactivate infectious ZIKV without disruption of Env. <b>Methods</b>: ZIKV was propagated in Vero cells and admixed with BCD. The BCD-treated ZIKV was evaluated for infectivity using immunofluorescence and quantitative RT-PCR (qRT-PCR) assays, for immunoreactivity in Western blots, structural integrity by electron microscopy, and immunogenicity in mice. <b>Results</b>: Here, we show that 200 mM BCD-treated ZIKV is non-infectious in cell culture, remains immunoreactive with an Env-specific antibody, retains its virion shape and size, and elicits the production of immunogen-specific antibodies in immunized mice. <b>Conclusions</b>: These results indicate that BCD can be used to safely inactivate ZIKV, and they provide insights for vaccine and antibody development.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769224/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of RT-PCR Assays for Simple Detection and Identification of Sabin Virus Contaminants in the Novel Oral Poliovirus Vaccines.","authors":"Olga Singh, Hasmik Manukyan, Erman Tritama, Shwu-Maan Lee, Jerry P Weir, Majid Laassri","doi":"10.3390/vaccines13010075","DOIUrl":"10.3390/vaccines13010075","url":null,"abstract":"<p><strong>Background/objectives: </strong>Conventional live oral poliovirus vaccines (OPVs) effectively prevent poliomyelitis. These vaccines are derived from three attenuated Sabin strains of poliovirus, which can revert within the first week of replication to a neurovirulent phenotype, leading to sporadic cases of vaccine-associated paralytic poliomyelitis (VAPP) among vaccinees and their contacts. A novel OPV2 vaccine (nOPV2) with enhanced genetic stability was developed recently; type 1 and type 3 nOPV strains were engineered using the nOPV2 genome as a backbone by replacing the capsid precursor polyprotein (P1) with that of Sabin strains type 1 and type 3, respectively. The nOPV vaccines have a high degree of sequence homology with the parental Sabin 2 genome, and some manufacturing facilities produce and store both Sabin OPV and nOPV. Therefore, detecting Sabin virus contaminations in nOPV lots is crucial.</p><p><strong>Methods: </strong>This study describes the development of pan quantitative reverse transcription polymerase chain reaction (panRT-PCR) and multiplex one-step RT-PCR (mosRT-PCR) assays for the straightforward detection and identification of contaminating Sabin viruses when present in significantly higher amounts of nOPV strains.</p><p><strong>Results: </strong>The two assays exhibit high specificity, reproducibility, and sensitivity to detect 0.0001% and 0.00001% of Sabin viruses in nOPV, respectively. Additionally, an analysis of 12 trivalent nOPV formulation lots using both methods confirmed that the nOPV lots were free from Sabin virus contamination.</p><p><strong>Conclusions: </strong>The results demonstrated that the RT-PCR assays are sensitive and specific. These assays are relevant for quality control and lot release of nOPV vaccines.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single Dose of Attenuated Vaccinia Viruses Expressing H5 Hemagglutinin Affords Rapid and Long-Term Protection Against Lethal Infection with Highly Pathogenic Avian Influenza A H5N1 Virus in Mice and Monkeys.","authors":"Fumihiko Yasui, Keisuke Munekata, Tomoko Fujiyuki, Takeshi Kuraishi, Kenzaburo Yamaji, Tomoko Honda, Sumiko Gomi, Misako Yoneda, Takahiro Sanada, Koji Ishii, Yoshihiro Sakoda, Hiroshi Kida, Shosaku Hattori, Chieko Kai, Michinori Kohara","doi":"10.3390/vaccines13010074","DOIUrl":"10.3390/vaccines13010074","url":null,"abstract":"<p><strong>Background/objectives: </strong>In preparation for a potential pandemic caused by the H5N1 highly pathogenic avian influenza (HPAI) virus, pre-pandemic vaccines against several viral clades have been developed and stocked worldwide. Although these vaccines are well tolerated, their immunogenicity and cross-reactivity with viruses of different clades can be improved.</p><p><strong>Methods: </strong>To address this aspect, we generated recombinant influenza vaccines against H5-subtype viruses using two different strains of highly attenuated vaccinia virus (VACV) vectors.</p><p><strong>Results: </strong>rLC16m8-mcl2.2 hemagglutinin (HA) and rLC16m8-mcl2.3.4 HA consisted of a recombinant LC16m8 vector encoding the HA protein from clade 2.2 or clade 2.3.4 viruses (respectively); rDIs-mcl2.2 HA consisted of a recombinant DIs vector encoding the HA protein from clade 2.2. A single dose of rLC16m8-mcl2.2 HA showed rapid (1 week after vaccination) and long-term protection (20 months post-vaccination) in mice against the HPAI H5N1 virus. Moreover, cynomolgus macaques immunized with rLC16m8-mcl2.2 HA exhibited long-term protection when challenged with a heterologous clade of the HPAI H5N1 virus. Although the DIs strain is unable to grow in most mammalian cells, rDIs-mcl2.2 HA also showed rapid and long-lasting effects against HPAI H5N1 virus infection. Notably, the protective efficacy of rDIs-mcl2.2 HA was comparable to that of rLC16m8-mcl2.2 HA. Furthermore, these vaccines protected animals previously immunized with VACVs from a lethal challenge with the HPAI H5N1 virus.</p><p><strong>Conclusions: </strong>These results suggest that both rLC16m8-mcl2.2 HA and rDIs-mcl2.2 HA are effective in preventing HPAI H5N1 virus infection, and rDIs-mcl2.2 HA is a promising vaccine candidate against H5 HA-subtype viruses.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Seasonal Influenza Vaccination Uptake Among Australian Healthcare Professionals: An Archetype for Success.","authors":"Caroline M Hall, Anthony Cotton, Adrian Webster, Mary Bushell, Holly L Northam","doi":"10.3390/vaccines13010071","DOIUrl":"10.3390/vaccines13010071","url":null,"abstract":"<p><strong>Background/objectives: </strong>Qualitative research suggests there may be identifiable characteristics that form a health professional (HCP) archetype associated with habitual seasonal influenza vaccination (SIV). However, the validity of this archetype requires further investigation, ideally within a theoretical framework that can elucidate this association and its generalisability to other vaccines. This study aims to confirm key HCP archetype characteristics associated with SIV, as informed by prior qualitative research findings, and test the generalisability of the association between this archetype and SIV to COVID-19 vaccine acceptance.</p><p><strong>Method: </strong>A cross-sectional survey was designed and distributed to an Australian HCP sample consisting of practicing nurses, midwives, pharmacists, and medical practitioners. The anonymous online survey measured key characteristics that predict vaccination behaviour and intention.</p><p><strong>Results: </strong>Most participants (n = 173) demonstrated habitual SIV behaviour (77.91%) associated with the intention to vaccinate in the future. Survey findings supported the HCP archetype, as key constructs were associated with vaccination intention and behaviour, including heightened professional responsibility, vaccine confidence, and protection of self and patients. Furthermore, results suggested progressing vaccination intention to behaviour, overcoming vaccine complacency, is possible through the provision of free, accessible vaccination services. These critical factors were broadly generalisable to the COVID-19 vaccine.</p><p><strong>Conclusions: </strong>A vaccination-positive HCP archetype, supported by access to free, convenient vaccination services, was associated with the likelihood of future vaccination behaviour, including in future pandemic response scenarios. However, it will be important to ensure that HCP vaccine knowledge gaps are minimised to enhance trust in this cohort to enable broad success.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategic and Technical Considerations in Manufacturing Viral Vector Vaccines for the Biomedical Advanced Research and Development Authority Threats.","authors":"Lindsay A Parish, Shyam Rele, Kimberly A Hofmeyer, Brooke B Luck, Daniel N Wolfe","doi":"10.3390/vaccines13010073","DOIUrl":"10.3390/vaccines13010073","url":null,"abstract":"<p><p>Over the past few decades, the world has seen a considerable uptick in the number of new and emerging infectious disease outbreaks. The development of new vaccines, vaccine technologies, and platforms are critical to enhance our preparedness for biological threats and prevent future pandemics. Viral vectors can be an important tool in the repertoire of technologies available to develop effective vaccines against new and emerging infectious diseases. In many instances, vaccines may be needed in a reactive scenario, requiring technologies than can elicit rapid and robust immune responses with a single dose. Here, we discuss how viral vector vaccines are utilized in a vaccine portfolio for priority biological threats, some of the challenges in manufacturing viral vector vaccines, the need to strengthen live virus manufacturing capabilities, and future opportunities to capitalize on the use of viral vectors to improve the sustainability of the Biomedical Advanced Research and Development Authority's vaccine portfolio.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploitation of Unconventional CD8 T-Cell Responses Induced by Engineered Cytomegaloviruses for the Development of an HIV-1 Vaccine.","authors":"Joseph Bruton, Tomáš Hanke","doi":"10.3390/vaccines13010072","DOIUrl":"10.3390/vaccines13010072","url":null,"abstract":"<p><p>After four decades of intensive research, traditional vaccination strategies for HIV-1 remain ineffective due to HIV-1's extraordinary genetic diversity and complex immune evasion mechanisms. Cytomegaloviruses (CMV) have emerged as a novel type of vaccine vector with unique advantages due to CMV persistence and immunogenicity. Rhesus macaques vaccinated with molecular clone 68-1 of RhCMV (RhCMV68-1) engineered to express simian immunodeficiency virus (SIV) immunogens elicited an unconventional major histocompatibility complex class Ib allele E (MHC-E)-restricted CD8⁺ T-cell response, which consistently protected over half of the animals against a highly pathogenic SIV challenge. The RhCMV68-1.SIV-induced responses mediated a post-infection replication arrest of the challenge virus and eventually cleared it from the body. These observations in rhesus macaques opened a possibility that MHC-E-restricted CD8⁺ T-cells could achieve similar control of HIV-1 in humans. The potentially game-changing advantage of the human CMV (HCMV)-based vaccines is that they would induce protective CD8⁺ T-cells persisting at the sites of entry that would be insensitive to HIV-1 evasion. In the RhCMV68-1-protected rhesus macaques, MHC-E molecules and their peptide cargo utilise complex regulatory mechanisms and unique transport patterns, and researchers study these to guide human vaccine development. However, CMVs are highly species-adapted viruses and it is yet to be shown whether the success of RhCMV68-1 can be translated into an HCMV ortholog for humans. Despite some safety concerns regarding using HCMV as a vaccine vector in humans, there is a vision of immune programming of HCMV to induce pathogen-tailored CD8⁺ T-cells effective against HIV-1 and other life-threatening diseases.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T4 Phage Displaying Dual Antigen Clusters Against H3N2 Influenza Virus Infection.","authors":"Shenglong Liu, Mengzhou Lin, Xin Zhou","doi":"10.3390/vaccines13010070","DOIUrl":"10.3390/vaccines13010070","url":null,"abstract":"<p><strong>Background: </strong>The current H3N2 influenza subunit vaccine exhibits weak immunogenicity, which limits its effectiveness in preventing and controlling influenza virus infections.</p><p><strong>Methods: </strong>In this study, we aimed to develop a T4 phage-based nanovaccine designed to enhance the immunogenicity of two antigens by displaying the HA1 and M2e antigens of the H3N2 influenza virus on each phage nanoparticle. Specifically, we fused the Soc protein with the HA1 antigen and the Hoc protein with the M2e antigen, assembling them onto a T4 phage that lacks Soc and Hoc proteins (Soc^-Hoc^-T4), thereby constructing a nanovaccine that concurrently presents both HA1 and M2e antigens.</p><p><strong>Results: </strong>The analysis of the optical density of the target protein bands indicated that each particle could display approximately 179 HA1 and 68 M2e antigen molecules. Additionally, animal experiments demonstrated that this nanoparticle vaccine displaying dual antigen clusters induced a stronger specific immune response, higher antibody titers, a more balanced Th1/Th2 immune response, and enhanced CD4⁺ and CD8⁺ T cell effects compared to immunization with HA1 and M2e antigen molecules alone. Importantly, mice immunized with the T4 phage displaying dual antigen clusters achieved full protection (100% protection) against the H3N2 influenza virus, highlighting its robust protective efficacy.</p><p><strong>Conclusions: </strong>In summary, our findings indicate that particles based on a T4 phage displaying antigen clusters exhibit ideal immunogenicity and protective effects, providing a promising strategy for the development of subunit vaccines against various viruses beyond influenza.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11769387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing Antibody Responses to Homologous vs. Heterologous COVID-19 Vaccination: A Cross-Sectional Analysis in an Urban Bangladeshi Population.","authors":"Kazi Istiaque Sanin, Mansura Khanam, Azizur Rahman Sharaque, Mahbub Elahi, Bharati Rani Roy, Md Khaledul Hasan, Goutam Kumar Dutta, Abir Dutta, Md Nazmul Islam, Md Safiqul Islam, Md Nasir Ahmed Khan, Mustufa Mahmud, Nuzhat Nadia, Fablina Noushin, Anjan Kumar Roy, Protim Sarker, Fahmida Tofail","doi":"10.3390/vaccines13010067","DOIUrl":"10.3390/vaccines13010067","url":null,"abstract":"<p><strong>Background: </strong>Vaccination has played a crucial role in mitigating the spread of COVID-19 and reducing its severe outcomes. While over 90% of Bangladesh's population has received at least one COVID-19 vaccine dose, the comparative effectiveness of homologous versus heterologous booster strategies, along with the complex interplay of factors within the population, remains understudied. This study aimed to compare antibody responses between these booster approaches.</p><p><strong>Methods: </strong>This cross-sectional study enrolled 723 adults in urban Dhaka who had received COVID-19 booster doses within the last six months. Participants were grouped based on homologous or heterologous booster vaccination. Data were collected through structured household surveys, and 2 mL blood samples were collected for measuring antibody titers.</p><p><strong>Results: </strong>Heterologous booster recipients showed higher median antibody titers (8597.0 U/mL, IQR 5053.0-15,482.3) compared to homologous recipients (6958.0 U/mL, IQR 3974.0-12,728.5). In the adjusted analysis, the type of booster dose had no significant impact on antibody levels. However, the duration since the last booster dose was significantly associated with antibody levels, where each additional month since receiving the booster corresponded to approximately a 15-16% reduction in antibody levels (Adj. coeff: 0.85, 95% CI: 0.81, 0.88; <i>p</i> < 0.001). Participants over 40 years demonstrated higher antibody levels than younger individuals (Adj. coeff: 1.23, 95% CI: 1.07, 1.43; <i>p</i> = 0.005). Sex, BMI, and prior COVID-19 infection showed no significant associations with antibody levels after adjustment.</p><p><strong>Conclusion: </strong>The results underscore the complexity of immune responses across different demographic groups and suggest potential benefits of ongoing heterologous booster strategies in sustaining immunity.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Evaluation of the Immunogenic Potential of an Unmodified Nucleoside mRNA Vaccine for Herpes Zoster.","authors":"Shun Zhang, Xiaojie Wang, Tongyi Zhao, Chen Yang, Lulu Huang","doi":"10.3390/vaccines13010068","DOIUrl":"10.3390/vaccines13010068","url":null,"abstract":"<p><strong>Background/objectives: </strong>Approved mRNA vaccines commonly use sequences modified with pseudouridine to enhance translation efficiency and mRNA stability. However, this modification can result in ribosomal frameshifts, reduced immunogenicity, and higher production costs. This study aimed to explore the potential of unmodified mRNA sequences for varicella-zoster virus (VZV) and evaluate whether codon optimization could overcome the limitations of pseudouridine modification.</p><p><strong>Methods: </strong>We utilized artificial intelligence (AI) to design several unmodified gE mRNA sequences for VZV, considering factors such as codon preference and secondary structure. The optimized mRNA sequences were assessed for protein expression levels in vitro and were subsequently used to develop a vaccine, named Vac07, encapsulated in a lipid nanoparticle (LNP) delivery system. The immunogenicity of Vac07 was evaluated in mice.</p><p><strong>Results: </strong>Codon-optimized mRNA sequences showed significantly higher protein expression levels in vitro compared to wild-type (WT) sequences. Vaccination with Vac07 demonstrated immunogenicity in mice that was comparable to, or even superior to, the licensed Shingrix vaccine, characterized by a stronger Th1-biased antibody response and a slightly more robust Th1-type cellular response.</p><p><strong>Conclusions: </strong>Codon-optimized unmodified mRNA sequences may also represent a viable approach for mRNA vaccine development. These optimized sequences have the potential to lower production costs while possibly enhancing the immunogenicity of mRNA vaccines. Vac07, developed using this method, shows promise as a potentially more efficient and cost-effective mRNA vaccine candidate for VZV.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Anti-Cancer Immune Responses Elicited Using Tumor-Targeted IL-2 Cytokine and Its Derivatives in Combined Preclinical Therapies.","authors":"Sahar Balkhi, Giorgia Bilato, Andrea De Lerma Barbaro, Paola Orecchia, Alessandro Poggi, Lorenzo Mortara","doi":"10.3390/vaccines13010069","DOIUrl":"10.3390/vaccines13010069","url":null,"abstract":"<p><p>Effective cancer therapies must address the tumor microenvironment (TME), a complex network of tumor cells and stromal components, including endothelial, immune, and mesenchymal cells. Durable outcomes require targeting both tumor cells and the TME while minimizing systemic toxicity. Interleukin-2 (IL-2)-based therapies have shown efficacy in cancers such as metastatic melanoma and renal cell carcinoma but are limited by severe side effects. Innovative IL-2-based immunotherapeutic approaches include immunotoxins, such as antibody-drug conjugates, immunocytokines, and antibody-cytokine fusion proteins that enhance tumor-specific delivery. These strategies activate cytotoxic CD8⁺ T lymphocytes and natural killer (NK) cells, eliciting a potent Th1-mediated anti-tumor response. Modified IL-2 variants with reduced Treg cell activity further improve specificity and reduce immunosuppression. Additionally, IL-2 conjugates with peptides or anti-angiogenic agents offer improved therapeutic profiles. Combining IL-2-based therapies with immune checkpoint inhibitors (ICIs), anti-angiogenic agents, or radiotherapy has demonstrated synergistic potential. Preclinical and clinical studies highlight reduced toxicity and enhanced anti-tumor efficacy, overcoming TME-driven immune suppression. These approaches mitigate the limitations of high-dose soluble IL-2 therapy, promoting immune activation and minimizing adverse effects. This review critically explores advances in IL-2-based therapies, focusing on immunotoxins, immunocytokines, and IL-2 derivatives. Emphasis is placed on their role in combination strategies, showcasing their potential to target the TME and improve clinical outcomes effectively. Also, the use of IL-2 immunocytokines in \"in situ\" vaccination to relieve the immunosuppression of the TME is discussed.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11768832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143033558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}