Pub Date : 2025-12-05DOI: 10.3390/vaccines13121226
Jiayu Zhao, Juan Shao, Xiuwen Sui, Menghan Wei, Xinjian Ma, Zhijun Xu, Tao Zhu
Background/Objectives: Varicella-zoster virus (VZV) causes herpes zoster (HZ/shingles), particularly in older adults with weakened cell-mediated immunity (CMI), which is essential for controlling VZV reactivation and reducing HZ severity. Currently vaccines, like recombinant subunit or live-attenuated vaccine, showed shortcomings in eliciting CD8+ T-cell responses. Addressing this, we utilized the novel replication-defective chimpanzee adenovirus vector ChAdOx1 to construct the ChAdOx1-VZV (CVE) vaccine, using full-length glycoprotein E (gE) as antigen. This study evaluated the immunogenicity of a heterologous intramuscular (IM) prime/intranasal (IN) boost regimen with the aim of developing a novel VZV vaccine candidate. Methods: BALB/c mice were immunized with CVE using homologous or heterologous prime-boost regimens via IM or IN. And cynomolgus macaques were immunized intramuscularly with three doses of CVE. Cellular responses were assessed by intracellular cytokine staining (ICS) and IFN-γ ELISpot using splenocytes and PBMCs. Humoral responses were evaluated by serum gE-IgG ELISA and bone-marrow LLPC ELISpot. Memory subsets and tissue-resident T cells were analyzed by flow cytometry. Results: Heterologous IM prime/IN boost CVE regimen markedly enhanced both cellular and humoral responses, especially CD8+ T-cell responses. The induced LLPC and memory T cell responses indicate the potential for long-term protection against herpes zoster. In cynomolgus macaques, CVE induced robust serum gE-specific IgG responses and strong IFN-γ secreting T-cell activity, supporting the immunogenicity of CVE in a genetically distinct primate model and enhancing its clinical translational potential. Conclusions: CVE induces potent cellular and humoral immunogenicity, with IM prime/IN boost vaccination. Cross species immunogenicity observed in nonhuman primates further strengthens the translational relevance of this platform. These findings support CVE as a promising herpes zoster vaccine candidate and provide a rationale for continued evaluation in human-relevant systems.
{"title":"Heterologous Prime-Boost with ChAdOx1-VZV Establishes Dual-Layer Immunogenicity Conferring Protective Potential Against Herpes Zoster.","authors":"Jiayu Zhao, Juan Shao, Xiuwen Sui, Menghan Wei, Xinjian Ma, Zhijun Xu, Tao Zhu","doi":"10.3390/vaccines13121226","DOIUrl":"10.3390/vaccines13121226","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Varicella-zoster virus (VZV) causes herpes zoster (HZ/shingles), particularly in older adults with weakened cell-mediated immunity (CMI), which is essential for controlling VZV reactivation and reducing HZ severity. Currently vaccines, like recombinant subunit or live-attenuated vaccine, showed shortcomings in eliciting CD8<sup>+</sup> T-cell responses. Addressing this, we utilized the novel replication-defective chimpanzee adenovirus vector ChAdOx1 to construct the ChAdOx1-VZV (CVE) vaccine, using full-length glycoprotein E (gE) as antigen. This study evaluated the immunogenicity of a heterologous intramuscular (IM) prime/intranasal (IN) boost regimen with the aim of developing a novel VZV vaccine candidate. <b>Methods</b>: BALB/c mice were immunized with CVE using homologous or heterologous prime-boost regimens via IM or IN. And cynomolgus macaques were immunized intramuscularly with three doses of CVE. Cellular responses were assessed by intracellular cytokine staining (ICS) and IFN-γ ELISpot using splenocytes and PBMCs. Humoral responses were evaluated by serum gE-IgG ELISA and bone-marrow LLPC ELISpot. Memory subsets and tissue-resident T cells were analyzed by flow cytometry. <b>Results</b>: Heterologous IM prime/IN boost CVE regimen markedly enhanced both cellular and humoral responses, especially CD8<sup>+</sup> T-cell responses. The induced LLPC and memory T cell responses indicate the potential for long-term protection against herpes zoster. In cynomolgus macaques, CVE induced robust serum gE-specific IgG responses and strong IFN-γ secreting T-cell activity, supporting the immunogenicity of CVE in a genetically distinct primate model and enhancing its clinical translational potential. <b>Conclusions</b>: CVE induces potent cellular and humoral immunogenicity, with IM prime/IN boost vaccination. Cross species immunogenicity observed in nonhuman primates further strengthens the translational relevance of this platform. These findings support CVE as a promising herpes zoster vaccine candidate and provide a rationale for continued evaluation in human-relevant systems.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820922","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}
Pub Date : 2025-12-05DOI: 10.3390/vaccines13121227
Silvia Valentini, Jurgen Sota, Irene Fineschi, Edoardo Conticini, Estrella Garcia-Gonzalez, Emilio D'Ignazio, Marco Bardelli, Stefano Gentileschi, Marta Fabbroni, Francesca Bellisai, Paolo Falsetti, Enrico Selvi, Luca Cantarini, Bruno Frediani, Caterina Baldi
Background: Patients with rheumatic diseases (RMDs) are at increased risk of herpes zoster (HZ), particularly when receiving immunosuppressive treatment. While recombinant zoster vaccine (RZV) has shown high effectiveness in the general population, evidence in rheumatologic patients remain limited due to their exclusion from pivotal trials.
Objectives: To evaluate the effectiveness of RZV and to collect additional safety data in a heterogeneous cohort of rheumatologic patients, compared with a control cohort from the general population.
Methods: We conducted a retrospective study including 179 adults who received two intramuscular doses of RZV between January 2021 and June 2025. The cohort included 114 patients with RMDs and 65 individuals from the general population. Effectiveness was defined as the ability to prevent HZ reactivation while safety concerns were recorded as any adverse event temporally associated with the vaccination.
Results: We observed a statistically significant reduction in terms of VZV relapses following vaccination (p < 0.001). Among patients diagnosed with RMDs, only one case of HZ recurrence was observed 14 weeks after vaccination, with no significant difference compared to general care patients. One patient experienced a disease flare requiring glucocorticosteroids. RZV demonstrated a favourable safety profile, with minor adverse events (fever, injection-site reactions, headache and myalgia) reported in 17.5% of patients after the first dose and 21.5% after the second. No significant association was observed between adverse events and advanced immunosuppressive therapy.
Conclusions: RZV displayed an effective and reassuring safety profile in a heterogeneous cohort of patients affected by RMDs, irrespective of the diagnosis and the ongoing therapy. This supports the broader use of RZV as a safe and valuable preventive strategy in patients with RMDs.
{"title":"Effectiveness and Safety of Recombinant Zoster Vaccine in Rheumatic Diseases: Real-World Evidence from a Single-Centre Italian Cohort.","authors":"Silvia Valentini, Jurgen Sota, Irene Fineschi, Edoardo Conticini, Estrella Garcia-Gonzalez, Emilio D'Ignazio, Marco Bardelli, Stefano Gentileschi, Marta Fabbroni, Francesca Bellisai, Paolo Falsetti, Enrico Selvi, Luca Cantarini, Bruno Frediani, Caterina Baldi","doi":"10.3390/vaccines13121227","DOIUrl":"10.3390/vaccines13121227","url":null,"abstract":"<p><strong>Background: </strong>Patients with rheumatic diseases (RMDs) are at increased risk of herpes zoster (HZ), particularly when receiving immunosuppressive treatment. While recombinant zoster vaccine (RZV) has shown high effectiveness in the general population, evidence in rheumatologic patients remain limited due to their exclusion from pivotal trials.</p><p><strong>Objectives: </strong>To evaluate the effectiveness of RZV and to collect additional safety data in a heterogeneous cohort of rheumatologic patients, compared with a control cohort from the general population.</p><p><strong>Methods: </strong>We conducted a retrospective study including 179 adults who received two intramuscular doses of RZV between January 2021 and June 2025. The cohort included 114 patients with RMDs and 65 individuals from the general population. Effectiveness was defined as the ability to prevent HZ reactivation while safety concerns were recorded as any adverse event temporally associated with the vaccination.</p><p><strong>Results: </strong>We observed a statistically significant reduction in terms of VZV relapses following vaccination (<i>p</i> < 0.001). Among patients diagnosed with RMDs, only one case of HZ recurrence was observed 14 weeks after vaccination, with no significant difference compared to general care patients. One patient experienced a disease flare requiring glucocorticosteroids. RZV demonstrated a favourable safety profile, with minor adverse events (fever, injection-site reactions, headache and myalgia) reported in 17.5% of patients after the first dose and 21.5% after the second. No significant association was observed between adverse events and advanced immunosuppressive therapy.</p><p><strong>Conclusions: </strong>RZV displayed an effective and reassuring safety profile in a heterogeneous cohort of patients affected by RMDs, irrespective of the diagnosis and the ongoing therapy. This supports the broader use of RZV as a safe and valuable preventive strategy in patients with RMDs.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821127","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}
Pub Date : 2025-12-04DOI: 10.3390/vaccines13121225
Amal Naji, Hana M El Sahly, Jennifer A Whitaker
Vaccines have been pivotal in reducing the incidence and severity of infectious diseases, improving population health, and lowering mortality rates globally. While substantial progress has been made in optimizing vaccine formulations, adjuvants, and schedules, comparatively less attention has been given to how the site of vaccination may influence immunologic outcomes. This review examines the impact of the administration of prime and booster vaccine doses in the same (ipsilateral) versus the opposite arms (contralateral) on vaccine immunogenicity. We review animal model and human studies evaluating the impact of ipsilateral versus contralateral COVID-19 and non-COVID-19 vaccine boosting on immunologic outcomes with a focus on the germinal center response, antibody production, and T cell activation. While some studies suggest that ipsilateral administration may enhance the quality of germinal center B cell responses and antibody magnitude, data across different studies have been inconsistent. Relatively few studies have compared ipsilateral versus contralateral boosting, and differences in study design and outcomes have limited the ability to draw conclusions as to whether one is superior to the other. This review highlights a noteworthy and underexplored area in vaccinology and the need for future research to clarify whether ipsilateral/contralateral boosting strategies matter. To answer this question, high-quality, randomized controlled trials evaluating different types of vaccines that consider immunologic mechanisms, capture key time points and appropriate specimens, and evaluate early and long-term immunogenicity endpoints are required.
{"title":"A Review of the Effects of Ipsilateral or Contralateral Vaccine Boosting on the Adaptive Immune Response.","authors":"Amal Naji, Hana M El Sahly, Jennifer A Whitaker","doi":"10.3390/vaccines13121225","DOIUrl":"10.3390/vaccines13121225","url":null,"abstract":"<p><p>Vaccines have been pivotal in reducing the incidence and severity of infectious diseases, improving population health, and lowering mortality rates globally. While substantial progress has been made in optimizing vaccine formulations, adjuvants, and schedules, comparatively less attention has been given to how the site of vaccination may influence immunologic outcomes. This review examines the impact of the administration of prime and booster vaccine doses in the same (ipsilateral) versus the opposite arms (contralateral) on vaccine immunogenicity. We review animal model and human studies evaluating the impact of ipsilateral versus contralateral COVID-19 and non-COVID-19 vaccine boosting on immunologic outcomes with a focus on the germinal center response, antibody production, and T cell activation. While some studies suggest that ipsilateral administration may enhance the quality of germinal center B cell responses and antibody magnitude, data across different studies have been inconsistent. Relatively few studies have compared ipsilateral versus contralateral boosting, and differences in study design and outcomes have limited the ability to draw conclusions as to whether one is superior to the other. This review highlights a noteworthy and underexplored area in vaccinology and the need for future research to clarify whether ipsilateral/contralateral boosting strategies matter. To answer this question, high-quality, randomized controlled trials evaluating different types of vaccines that consider immunologic mechanisms, capture key time points and appropriate specimens, and evaluate early and long-term immunogenicity endpoints are required.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820925","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}
Pub Date : 2025-12-03DOI: 10.3390/vaccines13121224
Anna M Timofeeva, Sergey E Sedykh, Georgy A Nevinsky
Background: Antibodies have the unique ability to recognize antigens and to be recognized as antigens by other antibodies, creating a balanced network that regulates the humoral part of the immune system. An antibody that uniquely identifies another antibody of a given specificity as its antigen is referred to as an anti-idiotypic antibody. Methods: A descriptive literature review was conducted using the PubMed database, including publications up to 2025. Results: This review examines the formation mechanisms of anti-idiotypic antibodies, their functional attributes, and their importance in diverse pathologies. A key focus is their capacity to neutralize pathogenic autoantibodies, offering a novel strategy for treating autoimmune diseases. Conversely, the generation of anti-Id Abs against therapeutic monoclonal antibodies (anti-drug antibodies) represents a significant challenge for biologic therapy, a complication addressed in a dedicated section on detection methods. Furthermore, consideration is given to the application of anti-Id Abs as innovative tools for vaccine design, particularly in oncology. By mimicking tumor-associated antigens, anti-Id Abs can induce a potent, targeted immune response against cancer with minimal side effects, presenting an alternative to conventional chemotherapy and radiation. Conclusions: Anti-Id Abs hold significant therapeutic promise. Their ability to selectively suppress pathogenic autoantibodies allows for precise immune intervention without broad immunosuppression. Additionally, their utility extends to vaccine development for various diseases. Further research into anti-Id Abs will deepen our understanding of immune regulation and open new avenues for targeted therapies.
{"title":"Anti-Idiotypic Antibodies in Immune Regulation and Disease: Therapeutic Promise for Next-Generation Vaccines.","authors":"Anna M Timofeeva, Sergey E Sedykh, Georgy A Nevinsky","doi":"10.3390/vaccines13121224","DOIUrl":"10.3390/vaccines13121224","url":null,"abstract":"<p><p><b>Background:</b> Antibodies have the unique ability to recognize antigens and to be recognized as antigens by other antibodies, creating a balanced network that regulates the humoral part of the immune system. An antibody that uniquely identifies another antibody of a given specificity as its antigen is referred to as an anti-idiotypic antibody. <b>Methods:</b> A descriptive literature review was conducted using the PubMed database, including publications up to 2025. <b>Results:</b> This review examines the formation mechanisms of anti-idiotypic antibodies, their functional attributes, and their importance in diverse pathologies. A key focus is their capacity to neutralize pathogenic autoantibodies, offering a novel strategy for treating autoimmune diseases. Conversely, the generation of anti-Id Abs against therapeutic monoclonal antibodies (anti-drug antibodies) represents a significant challenge for biologic therapy, a complication addressed in a dedicated section on detection methods. Furthermore, consideration is given to the application of anti-Id Abs as innovative tools for vaccine design, particularly in oncology. By mimicking tumor-associated antigens, anti-Id Abs can induce a potent, targeted immune response against cancer with minimal side effects, presenting an alternative to conventional chemotherapy and radiation. <b>Conclusions:</b> Anti-Id Abs hold significant therapeutic promise. Their ability to selectively suppress pathogenic autoantibodies allows for precise immune intervention without broad immunosuppression. Additionally, their utility extends to vaccine development for various diseases. Further research into anti-Id Abs will deepen our understanding of immune regulation and open new avenues for targeted therapies.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821012","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}
Pub Date : 2025-12-03DOI: 10.3390/vaccines13121223
Massimo Vicentini, Pamela Mancuso, Francesco Venturelli, Sergio Mezzadri, Eufemia Bisaccia, Alessandro Zerbini, Lucia Mangone, Paolo Giorgi Rossi, On Behalf Of The Reggio Emilia Covid-Working Group
Background: Cancer patients are particularly vulnerable to severe outcomes from COVID-19 due to immune suppression, treatment effects, and comorbidities. This population-based study aimed to assess how vaccination, circulating variants, and comorbidities influenced infections and severe disease risks in cancer patients compared with the general population. Methods: The study included 538,516 residents of Reggio Emilia Province, Italy, alive on 20 February 2020, followed until 30 September 2022. Cancer diagnoses (1996-2021) were obtained from the Reggio Emilia Cancer Registry and linked with COVID-19 surveillance, vaccination, hospitalization, and mortality data. Vaccination and prior infection were modelled as time-dependent variables. Hazard ratios for infection (HRs) and odds ratios for severe disease in those infected (ORs) were estimated using Cox and logistic regression models adjusting for sex, age, and comorbidities. Results: Among the 33,307 residents who had cancer, 9135 SARS-CoV-2 infections were recorded. Infection risk was similar to the general population before Omicron (HR 1.00; 95%CI 0.96-1.05) and slightly higher during Omicron (HR 1.08; 95%CI 1.05-1.11). Cancer patients showed higher probability of severe disease once infected (OR 1.33 pre-Omicron; 1.67 Omicron), with the greatest excess in recent diagnoses. Vaccination substantially reduced infections and severe outcomes in both groups in the pre-Omicron period; while only hybrid immunity reached high protection from Omicron infection. Conclusions: Vaccinations were effective in the populations with and without cancer; hybrid immunity conferred the strongest protection. However, because cancer patients, especially those recently diagnosed, retain a higher baseline risk of severe disease, vaccination yields even greater individual and public health benefits.
{"title":"Assessing COVID-19 Infection and Severe Disease Risk in Cancer Patients and Survivors: The Role of Vaccination Status, Circulating Variants, and Comorbidities-A Population-Based Study in Northern Italy.","authors":"Massimo Vicentini, Pamela Mancuso, Francesco Venturelli, Sergio Mezzadri, Eufemia Bisaccia, Alessandro Zerbini, Lucia Mangone, Paolo Giorgi Rossi, On Behalf Of The Reggio Emilia Covid-Working Group","doi":"10.3390/vaccines13121223","DOIUrl":"10.3390/vaccines13121223","url":null,"abstract":"<p><p><b>Background</b>: Cancer patients are particularly vulnerable to severe outcomes from COVID-19 due to immune suppression, treatment effects, and comorbidities. This population-based study aimed to assess how vaccination, circulating variants, and comorbidities influenced infections and severe disease risks in cancer patients compared with the general population. <b>Methods</b>: The study included 538,516 residents of Reggio Emilia Province, Italy, alive on 20 February 2020, followed until 30 September 2022. Cancer diagnoses (1996-2021) were obtained from the Reggio Emilia Cancer Registry and linked with COVID-19 surveillance, vaccination, hospitalization, and mortality data. Vaccination and prior infection were modelled as time-dependent variables. Hazard ratios for infection (HRs) and odds ratios for severe disease in those infected (ORs) were estimated using Cox and logistic regression models adjusting for sex, age, and comorbidities. <b>Results</b>: Among the 33,307 residents who had cancer, 9135 SARS-CoV-2 infections were recorded. Infection risk was similar to the general population before Omicron (HR 1.00; 95%CI 0.96-1.05) and slightly higher during Omicron (HR 1.08; 95%CI 1.05-1.11). Cancer patients showed higher probability of severe disease once infected (OR 1.33 pre-Omicron; 1.67 Omicron), with the greatest excess in recent diagnoses. Vaccination substantially reduced infections and severe outcomes in both groups in the pre-Omicron period; while only hybrid immunity reached high protection from Omicron infection. <b>Conclusions</b>: Vaccinations were effective in the populations with and without cancer; hybrid immunity conferred the strongest protection. However, because cancer patients, especially those recently diagnosed, retain a higher baseline risk of severe disease, vaccination yields even greater individual and public health benefits.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821093","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}
Pub Date : 2025-12-03DOI: 10.3390/vaccines13121222
Olivia Roy, Karen S Anderson
The landscape of cancer immunotherapy has been redefined by mRNA vaccines as rapid clinically viable strategies that help induce potent, tumor-specific immune responses. This review highlights the current advances in mRNA engineering and antigen design to establish an integrated immunological framework for cancer vaccine development. Achieving durable clinical benefit requires more than antigen expression. Effective vaccines need precise epitope selection, optimized delivery systems, and rigorous immune monitoring. The field is shifting from merely inducing immune responses to focusing more on the biochemistry and molecular design principles that combine magnitude, polyfunctionality, and longevity to overcome tumor-induced immune suppression. We examine an integrated immunological framework for mRNA cancer vaccine development, examining how rational molecular engineering of vaccine components, from nucleoside modifications and codon optimization to untranslated regions and linker sequences, shapes immunogenicity and therapeutic efficacy. Future directions will depend on balancing combinatorial strategies combining vaccination with immune checkpoint inhibitors and adoptive cell therapies.
{"title":"Engineering Anti-Tumor Immunity: An Immunological Framework for mRNA Cancer Vaccines.","authors":"Olivia Roy, Karen S Anderson","doi":"10.3390/vaccines13121222","DOIUrl":"10.3390/vaccines13121222","url":null,"abstract":"<p><p>The landscape of cancer immunotherapy has been redefined by mRNA vaccines as rapid clinically viable strategies that help induce potent, tumor-specific immune responses. This review highlights the current advances in mRNA engineering and antigen design to establish an integrated immunological framework for cancer vaccine development. Achieving durable clinical benefit requires more than antigen expression. Effective vaccines need precise epitope selection, optimized delivery systems, and rigorous immune monitoring. The field is shifting from merely inducing immune responses to focusing more on the biochemistry and molecular design principles that combine magnitude, polyfunctionality, and longevity to overcome tumor-induced immune suppression. We examine an integrated immunological framework for mRNA cancer vaccine development, examining how rational molecular engineering of vaccine components, from nucleoside modifications and codon optimization to untranslated regions and linker sequences, shapes immunogenicity and therapeutic efficacy. Future directions will depend on balancing combinatorial strategies combining vaccination with immune checkpoint inhibitors and adoptive cell therapies.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821166","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}
Pub Date : 2025-12-03DOI: 10.3390/vaccines13121221
Anna M Lyapina, Natalya V Kichemazova, Maxim S Lavrukhin, Yuri V Saltykov, Sergey S Zaytsev, Olga S Larionova, Valentina A Feodorova
Background/objectives: Lumpy skin disease (LSD) is a notifiable disease due to a marked potency for rapid spread and a significant negative economic impact on agriculture worldwide. As such, vaccination is considered the most effective way to control the disease in endemic countries, and the serological response to homologous LSDV-based vaccines is widely investigated. However, less is known about the seroconversion and duration of the immune response that is elicited by live attenuated heterologous vaccines based on the Sheeppox virus (SPPV) used for LSD prevention. This study aimed to investigate the humoral immune response in cattle immunized with a heterologous SPPV-based vaccine in the field.
Methods: Commercial ELISA, based on P32 protein, as well as immunoblotting, were used to assess the antibody response in 6-month-old, 17-month-old, and older animals before and after the first immunization and revaccination.
Results: Only a secondary immune response was detected when using commercial ELISA in revaccinated animals in each of the groups (83.3% and 30%, respectively). A comparative bioinformatic analysis proved a marked polymorphism of P32, derived from LSDV/SPPV/GTPV, which potentially resulted in negative responses in the ELISA. However, immunoblotting revealed a 100% seroconversion in vaccinated animals after the first vaccination and revaccination. Notably, specific antibodies were found in the sera of 80% of 6-month-old calves before the first vaccination, which had probably been passively transferred from their mothers, who were multiply vaccinated with SPPV-based vaccines.
Conclusions: Several immunodominant antigens were able to induce a humoral immune response in cattle to the SPPV-based vaccine after passive and active immunization, serving as promising markers for a humoral immune response to heterologous vaccines.
{"title":"Humoral Response in Cattle Vaccinated with the Heterologous Sheeppox Virus Vaccine for Protection Against Lumpy Skin Disease: A Field Study.","authors":"Anna M Lyapina, Natalya V Kichemazova, Maxim S Lavrukhin, Yuri V Saltykov, Sergey S Zaytsev, Olga S Larionova, Valentina A Feodorova","doi":"10.3390/vaccines13121221","DOIUrl":"10.3390/vaccines13121221","url":null,"abstract":"<p><strong>Background/objectives: </strong>Lumpy skin disease (LSD) is a notifiable disease due to a marked potency for rapid spread and a significant negative economic impact on agriculture worldwide. As such, vaccination is considered the most effective way to control the disease in endemic countries, and the serological response to homologous LSDV-based vaccines is widely investigated. However, less is known about the seroconversion and duration of the immune response that is elicited by live attenuated heterologous vaccines based on the Sheeppox virus (SPPV) used for LSD prevention. This study aimed to investigate the humoral immune response in cattle immunized with a heterologous SPPV-based vaccine in the field.</p><p><strong>Methods: </strong>Commercial ELISA, based on P32 protein, as well as immunoblotting, were used to assess the antibody response in 6-month-old, 17-month-old, and older animals before and after the first immunization and revaccination.</p><p><strong>Results: </strong>Only a secondary immune response was detected when using commercial ELISA in revaccinated animals in each of the groups (83.3% and 30%, respectively). A comparative bioinformatic analysis proved a marked polymorphism of P32, derived from LSDV/SPPV/GTPV, which potentially resulted in negative responses in the ELISA. However, immunoblotting revealed a 100% seroconversion in vaccinated animals after the first vaccination and revaccination. Notably, specific antibodies were found in the sera of 80% of 6-month-old calves before the first vaccination, which had probably been passively transferred from their mothers, who were multiply vaccinated with SPPV-based vaccines.</p><p><strong>Conclusions: </strong>Several immunodominant antigens were able to induce a humoral immune response in cattle to the SPPV-based vaccine after passive and active immunization, serving as promising markers for a humoral immune response to heterologous vaccines.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820927","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}
Pub Date : 2025-12-02DOI: 10.3390/vaccines13121219
Claudio Costantino, Emanuele Amodio, Rosario Asciutto, Costanza Affranchi, Franco Belbruno, Nicole Bonaccorso, Sonia Cilia, Fabio Massimo Contarino, Vincenzo Di Gaetano, Francesco Di Gregorio, Angelo Foresta, Roberto Furnari, Flavio Genna, Dario Genovese, Gabriele Giorgianni, Carmelo Massimo Maida, Sara Palmeri, Giovanna Parrino, Alessandra Piazza, Sebastiano Pollina Addario, Giovanni Tinervia, Fabio Tramuto, Francesco Vitale
Objectives: The introduction of universal prophylaxis with Nirsevimab represents a major innovation in preventing respiratory syncytial virus (RSV) infections in newborns. In Sicily, Nirsevimab administration began on 1 November 2024, for all newborns under one year and at-risk infants during the 2024-2025 season. This study assessed the real-world impact of this strategy in reducing RSV-related hospitalizations. Methods: This retrospective cohort study examined newborns residing in Sicily from 2015 to May 2025, evaluating hospitalization incidence rates attributable to RSV during the first year of life. RSV hospitalizations were identified using ICD-9 codes (079.6, 466.11, 480.1) in any diagnostic position. Incidence rates in the 2024-2025 season (intervention period) were compared with preceding seasons. Results: During the study period, 4431 RSV hospitalization cases occurred (19.84 cases per 1000 person-years), peaking in 2023-2024 (53.47 cases per 1000 person-years). A statistically significant 40% reduction in RSV hospitalizations was observed during the 2024-2025 season (October-April) compared with the preceding season, with a relative reduction ranging between 33.4% and 54.8% across sensitivity models. Conclusions: These results confirm the significant impact of the universal prophylaxis program in real-world practice, consistent with other European programs. These findings support universal RSV prevention strategies and provide insights for optimizing regional and national health policies.
{"title":"Impact of a Universal Nirsevimab Prevention Program Against Respiratory Syncytial Virus Bronchiolitis in Infants in Sicily (Italy) During the 2024-2025 Epidemic Season: A Retrospective Cohort Study.","authors":"Claudio Costantino, Emanuele Amodio, Rosario Asciutto, Costanza Affranchi, Franco Belbruno, Nicole Bonaccorso, Sonia Cilia, Fabio Massimo Contarino, Vincenzo Di Gaetano, Francesco Di Gregorio, Angelo Foresta, Roberto Furnari, Flavio Genna, Dario Genovese, Gabriele Giorgianni, Carmelo Massimo Maida, Sara Palmeri, Giovanna Parrino, Alessandra Piazza, Sebastiano Pollina Addario, Giovanni Tinervia, Fabio Tramuto, Francesco Vitale","doi":"10.3390/vaccines13121219","DOIUrl":"10.3390/vaccines13121219","url":null,"abstract":"<p><p><b>Objectives</b>: The introduction of universal prophylaxis with Nirsevimab represents a major innovation in preventing respiratory syncytial virus (RSV) infections in newborns. In Sicily, Nirsevimab administration began on 1 November 2024, for all newborns under one year and at-risk infants during the 2024-2025 season. This study assessed the real-world impact of this strategy in reducing RSV-related hospitalizations. <b>Methods</b>: This retrospective cohort study examined newborns residing in Sicily from 2015 to May 2025, evaluating hospitalization incidence rates attributable to RSV during the first year of life. RSV hospitalizations were identified using ICD-9 codes (079.6, 466.11, 480.1) in any diagnostic position. Incidence rates in the 2024-2025 season (intervention period) were compared with preceding seasons. <b>Results</b>: During the study period, 4431 RSV hospitalization cases occurred (19.84 cases per 1000 person-years), peaking in 2023-2024 (53.47 cases per 1000 person-years). A statistically significant 40% reduction in RSV hospitalizations was observed during the 2024-2025 season (October-April) compared with the preceding season, with a relative reduction ranging between 33.4% and 54.8% across sensitivity models. <b>Conclusions</b>: These results confirm the significant impact of the universal prophylaxis program in real-world practice, consistent with other European programs. These findings support universal RSV prevention strategies and provide insights for optimizing regional and national health policies.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820979","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}
Pub Date : 2025-12-02DOI: 10.3390/vaccines13121220
Ahmed Haji Said, Fiona Syed, Isabelle Ma, Rida Akbar, Nidhi Ramprasad, Erin E Reardon, Robert A Bednarczyk, Kate Winskell, Lavanya Vasudevan
Background: Interactive, narrative-based digital health interventions may positively influence vaccination-related attitudes, intentions, and uptake. However, evidence on their implementation and evaluation for vaccine communication has not yet been comprehensively synthesized. Our research questions (RQs) were to describe the use of interactive, narrative-based digital health interventions for vaccine communication (RQ1), their impact on individuals' vaccine intention or uptake (RQ2), and factors associated with their implementation (RQ3). Methods: A scoping review was conducted using Arksey and O'Malley's 5-stage framework and the PRISMA-ScR guidelines. We searched PubMed, Embase, Scopus, Web of Science, CINAHL, and PsycINFO from inception to 18 April 2023. To be included in the review, studies had to include empirical findings from primary data collection, address vaccine communication, use narrative communication that enabled audience engagement (i.e., interactivity), and deliver the narrative through a digital health device or modality. Results: The search identified 6834 records, with 25 studies meeting the inclusion criteria. For RQ1, the interventions most often focused on HPV vaccination (12 studies). Communication objectives included addressing vaccine hesitancy and increasing vaccination confidence or knowledge. Intervention delivery formats included multi-device compatibility (utilizing more than one device type, 7 studies) and incorporated interactive features, such as gamification and push notifications. Invented narratives were the most frequent narrative approach (8 studies). For RQ2, vaccination outcomes were reported in nearly half the studies (12 studies), with vaccination intention assessed in 8 studies and both vaccination intention and uptake assessed in 4 studies. For RQ3, implementation factors were reported in nearly half the studies (12 studies), with the most frequently reported outcome being acceptability (6 studies). Conclusions: Evidence supporting interactive, narrative-based digital health interventions for vaccine communication can be strengthened by diversifying narrative strategies, expanding the range of interactivity modalities tested, and focusing on a broader range of vaccines. Further research is needed to assess the effectiveness of these interventions, particularly of vaccine uptake. The insights from this scoping review may inform the development of novel future interventions for vaccine communication. The generalizability of these findings may be limited by the small number of studies in some categories and the preponderance of studies from high-income settings.
背景:交互式、基于叙述的数字卫生干预措施可能对疫苗接种相关的态度、意图和吸收产生积极影响。然而,关于疫苗传播的实施和评价的证据尚未得到全面综合。我们的研究问题(rq)是描述在疫苗沟通(RQ1)中使用交互式、基于叙述的数字健康干预措施,它们对个人疫苗意向或摄取(RQ2)的影响,以及与实施(RQ3)相关的因素。方法:采用Arksey和O'Malley的5阶段框架和PRISMA-ScR指南进行范围审查。我们检索了PubMed, Embase, Scopus, Web of Science, CINAHL和PsycINFO从成立到2023年4月18日。要纳入审查,研究必须包括来自主要数据收集的实证结果,解决疫苗传播问题,使用能够使受众参与(即互动性)的叙事传播,并通过数字卫生设备或模式传递叙事。结果:检索到6834条记录,其中25项研究符合纳入标准。对于RQ1,干预措施通常集中于HPV疫苗接种(12项研究)。沟通目标包括解决疫苗犹豫问题和增加疫苗接种信心或知识。干预交付格式包括多设备兼容性(使用多种设备类型,7项研究),并结合互动功能,如游戏化和推送通知。虚构叙事是最常见的叙事方法(8项研究)。对于RQ2,近一半的研究(12项研究)报告了疫苗接种结果,8项研究评估了疫苗接种意图,4项研究评估了疫苗接种意图和摄取。对于RQ3,近一半的研究(12项研究)报告了实施因素,最常见的报告结果是可接受性(6项研究)。结论:可以通过多样化叙述策略、扩大所测试的互动模式的范围以及侧重于更广泛的疫苗,来加强支持用于疫苗传播的交互式、基于叙述的数字卫生干预的证据。需要进一步的研究来评估这些干预措施的有效性,特别是疫苗接种的有效性。这一范围审查的见解可能为未来疫苗传播的新型干预措施的发展提供信息。这些发现的普遍性可能受到某些类别的研究数量较少和高收入环境的研究优势的限制。
{"title":"Interactive, Narrative-Based Digital Health Interventions for Vaccine Communication: Scoping Review.","authors":"Ahmed Haji Said, Fiona Syed, Isabelle Ma, Rida Akbar, Nidhi Ramprasad, Erin E Reardon, Robert A Bednarczyk, Kate Winskell, Lavanya Vasudevan","doi":"10.3390/vaccines13121220","DOIUrl":"10.3390/vaccines13121220","url":null,"abstract":"<p><p><b>Background:</b> Interactive, narrative-based digital health interventions may positively influence vaccination-related attitudes, intentions, and uptake. However, evidence on their implementation and evaluation for vaccine communication has not yet been comprehensively synthesized. Our research questions (RQs) were to describe the use of interactive, narrative-based digital health interventions for vaccine communication (RQ1), their impact on individuals' vaccine intention or uptake (RQ2), and factors associated with their implementation (RQ3). <b>Methods:</b> A scoping review was conducted using Arksey and O'Malley's 5-stage framework and the PRISMA-ScR guidelines. We searched PubMed, Embase, Scopus, Web of Science, CINAHL, and PsycINFO from inception to 18 April 2023. To be included in the review, studies had to include empirical findings from primary data collection, address vaccine communication, use narrative communication that enabled audience engagement (i.e., interactivity), and deliver the narrative through a digital health device or modality. <b>Results:</b> The search identified 6834 records, with 25 studies meeting the inclusion criteria. For RQ1, the interventions most often focused on HPV vaccination (12 studies). Communication objectives included addressing vaccine hesitancy and increasing vaccination confidence or knowledge. Intervention delivery formats included multi-device compatibility (utilizing more than one device type, 7 studies) and incorporated interactive features, such as gamification and push notifications. Invented narratives were the most frequent narrative approach (8 studies). For RQ2, vaccination outcomes were reported in nearly half the studies (12 studies), with vaccination intention assessed in 8 studies and both vaccination intention and uptake assessed in 4 studies. For RQ3, implementation factors were reported in nearly half the studies (12 studies), with the most frequently reported outcome being acceptability (6 studies). <b>Conclusions:</b> Evidence supporting interactive, narrative-based digital health interventions for vaccine communication can be strengthened by diversifying narrative strategies, expanding the range of interactivity modalities tested, and focusing on a broader range of vaccines. Further research is needed to assess the effectiveness of these interventions, particularly of vaccine uptake. The insights from this scoping review may inform the development of novel future interventions for vaccine communication. The generalizability of these findings may be limited by the small number of studies in some categories and the preponderance of studies from high-income settings.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145821052","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}
Pub Date : 2025-12-01DOI: 10.3390/vaccines13121218
Landon Myer, Emily Wasserman, Saiqa Tabasum, Emma Shittu, Yanping Liu, Lisa Jose, Elizea Horne, Robert S Moraba, Agatha Wilhase, Heather J Zar, Nazreen Hussen, Mokgadi S Mogashoa, Mookho Malahleha, Shabir A Madhi, Uzma N Sarwar, Hasra Snaggs, Rahsan Erdem, David Radley, Elena V Kalinina, Barbara A Pahud, Maria Maddalena Lino, Olympia Evdoxia Anastasiou, Kena A Swanson, Annaliesa S Anderson, Alejandra Gurtman, Iona Munjal
Background/Objectives: HIV-exposed uninfected (HEU) infants experience increased severe respiratory syncytial virus lower respiratory tract illness (RSV-LRTI) rates compared with HIV-unexposed infants. Maternal bivalent RSVpreF vaccination can prevent infant RSV-LRTI but data from HEU infants are lacking. Methods: This phase 3 randomized, double-blinded trial assessed RSVpreF safety and immunogenicity in pregnant participants from South Africa living with HIV and their infants. Maternal participants with stable HIV disease taking antiretroviral therapy received RSVpreF or placebo (24-36 weeks' gestation). Primary safety endpoints included reactogenicity through 7 days after vaccination (maternal participants), adverse events (AEs) through 1 month after vaccination (maternal participants) or birth (infants), and serious AEs (SAEs) throughout the study (maternal participants) or through 6 months after birth (infants). Immune responses were evaluated by 50% RSV-A and RSV-B neutralizing titers prevaccination and at delivery (maternal participants) or birth (infants). Results: Overall, 343 maternal participants received RSVpreF (n = 172) or placebo (n = 171). Most reactogenicity events were mild/moderate. AEs and SAEs were generally reported at similar frequencies in maternal RSVpreF and placebo groups including percentages of hypertensive disorders of pregnancy. There were no safety concerns in infants; percentages of reported AEs and SAEs were generally similar between RSVpreF and placebo groups and no difference in preterm birth. RSVpreF elicited high maternal neutralizing RSV-A and RSV-B immune responses, with efficient RSV antibody transplacental transfer to infants demonstrated by levels greater than the placebo group at birth (geometric mean ratios (GMRs) of RSVpreF to placebo were 7.8 for RSV-A and 6.8 for RSV-B) and by comparison with a cohort of HIV-unexposed infants from the pivotal phase 3 efficacy trial (GMRs of HEU to HIV-unexposed infants were 0.86 for RSV-A and 0.72 for RSV-B). Conclusions: These results support maternal RSVpreF vaccination among those living with stable HIV for preventing RSV-LRTI in HEU infants. (NCT06325657).
{"title":"Safety, Tolerability, and Immunogenicity of RSVpreF Vaccine in Pregnant Individuals Living with HIV.","authors":"Landon Myer, Emily Wasserman, Saiqa Tabasum, Emma Shittu, Yanping Liu, Lisa Jose, Elizea Horne, Robert S Moraba, Agatha Wilhase, Heather J Zar, Nazreen Hussen, Mokgadi S Mogashoa, Mookho Malahleha, Shabir A Madhi, Uzma N Sarwar, Hasra Snaggs, Rahsan Erdem, David Radley, Elena V Kalinina, Barbara A Pahud, Maria Maddalena Lino, Olympia Evdoxia Anastasiou, Kena A Swanson, Annaliesa S Anderson, Alejandra Gurtman, Iona Munjal","doi":"10.3390/vaccines13121218","DOIUrl":"10.3390/vaccines13121218","url":null,"abstract":"<p><p><b>Background/Objectives:</b> HIV-exposed uninfected (HEU) infants experience increased severe respiratory syncytial virus lower respiratory tract illness (RSV-LRTI) rates compared with HIV-unexposed infants. Maternal bivalent RSVpreF vaccination can prevent infant RSV-LRTI but data from HEU infants are lacking. <b>Methods:</b> This phase 3 randomized, double-blinded trial assessed RSVpreF safety and immunogenicity in pregnant participants from South Africa living with HIV and their infants. Maternal participants with stable HIV disease taking antiretroviral therapy received RSVpreF or placebo (24-36 weeks' gestation). Primary safety endpoints included reactogenicity through 7 days after vaccination (maternal participants), adverse events (AEs) through 1 month after vaccination (maternal participants) or birth (infants), and serious AEs (SAEs) throughout the study (maternal participants) or through 6 months after birth (infants). Immune responses were evaluated by 50% RSV-A and RSV-B neutralizing titers prevaccination and at delivery (maternal participants) or birth (infants). <b>Results:</b> Overall, 343 maternal participants received RSVpreF (<i>n</i> = 172) or placebo (<i>n</i> = 171). Most reactogenicity events were mild/moderate. AEs and SAEs were generally reported at similar frequencies in maternal RSVpreF and placebo groups including percentages of hypertensive disorders of pregnancy. There were no safety concerns in infants; percentages of reported AEs and SAEs were generally similar between RSVpreF and placebo groups and no difference in preterm birth. RSVpreF elicited high maternal neutralizing RSV-A and RSV-B immune responses, with efficient RSV antibody transplacental transfer to infants demonstrated by levels greater than the placebo group at birth (geometric mean ratios (GMRs) of RSVpreF to placebo were 7.8 for RSV-A and 6.8 for RSV-B) and by comparison with a cohort of HIV-unexposed infants from the pivotal phase 3 efficacy trial (GMRs of HEU to HIV-unexposed infants were 0.86 for RSV-A and 0.72 for RSV-B). <b>Conclusions:</b> These results support maternal RSVpreF vaccination among those living with stable HIV for preventing RSV-LRTI in HEU infants. (NCT06325657).</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"13 12","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12737651/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820654","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}