Human Vaccines & Immunotherapeutics

Human Vaccines & Immunotherapeutics

Published by Taylor & Francis

Online ISSN: 2164-554X

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Print ISSN: 2164-5515

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Cumulative global cases and deaths of human infections with H5N1, H7N9, and H9N2 avian influenza viruses reported to the World Health Organization (WHO). Cases and deaths are cumulative from the first reported case of each virus subtype in humans until February 22, 2024. Numbers on top of the bars indicate how many cases and deaths have been reported to the WHO. Note: as of February 22, 2024, two deaths have been reported from H9N2 infections according to the WHO. Due to the limited scale of the figure, these deaths are not visually represented, but the number is included in the graph.
(a) H5N1, H7N9, and H9N2 influenza subtypes from avian sources can infect humans and cause disease. Sustained human-to-human transmission of these subtypes has not been observed but is required to the emergence of pandemic viruses which could further spread within the human population. (b) vaccine development and vaccination of humans can prevent infections and the generation of pandemic viruses, improving pandemic preparedness and management against avian influenza viruses. This figure was created with BioRender.com.
of animal data for H5N1, H7N9, and H9N2 vaccines tested in mice, ferrets, and non-human primates. The figure categorizes vaccines by platform (inactivated, live attenuated, and alternative) and uses color-coded boxes for each category. It is important to note that only data from vaccines discussed in this review for each animal model are included. While other platforms exist, they are not discussed in detail within this manuscript. This figure was created with BioRender.com.
Pandemic preparedness through vaccine development for avian influenza viruses

May 2024

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11 Citations

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Understanding barriers to influenza vaccination among parents is important to improve vaccine uptake among children

January 2025

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The COVID-19 pandemic has significantly altered public perceptions of vaccines, particularly among parents. In high-income countries like the United Kingdom (UK) and Australia, factors such as misinformation, the expedited approval process of COVID-19 vaccines and unique local challenges have contributed to vaccine hesitancy, resulting in uneven uptake across various vaccination programs. Despite efforts like school-based influenza vaccination programs in the UK and free influenza vaccines in Australia, vaccination rates continue to decline. This is especially concerning given the concurrent circulation of COVID-19 and influenza during the winter months, which places additional strain on healthcare systems. Drawing on existing evidence, this commentary examines key factors influencing childhood vaccination rates and provides preliminary policy recommendations to address these challenges. Three actionable recommendations are outlined, including strategies to counter misinformation, improve accessibility, and strengthen public trust in vaccination programs. These insights aim to guide the development of effective interventions to increase vaccination uptake.

Aims and scope


Human Vaccines & Immunotherapeutics is an international journal of vaccinology and immunotherapy that publishes all aspects of work in these fields.

  • Human Vaccines & Immunotherapeutics publishes international research into vaccinology and immunotherapy, including novel and experimental vaccine exploration.
  • Human Vaccines & Immunotherapeutics is affiliated with the International Society for Vaccines (ISV).
  • The aim of Human Vaccines & Immunotherapeutics is to provide a platform to present and discuss developments in vaccinology and immunotherapy.
  • The journal covers the following topics: Research and development of novel vaccines and immunotherapeutics, Experimental vaccines and novel approaches in vaccination and immunotherapy, Vaccines and immunotherapeutics for treating non-infectious diseases, e.g., cancer, Preclinical studies and clinical trials, Licensed products and their use in the field, Impact of licensed vaccines and Immunotherapeutics on disease, Safety and perceptions of licensed vaccines, Prevention and treatment in the developing world, Epidemiology and pharmaco-economics.
  • Human Vaccines & Immunotherapeutics accepts brief reports, and …

For a full list of the subject areas this journal covers, please visit the journal website.

Recent articles


Analysis on willingness and its influencing factors of influenza vaccination among HCWs in Quzhou in 2022–2023 influenza season
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February 2025

Wangfeng Zheng

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Mei Lu

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Canya Fu

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Canjie Zheng



Illustration of risk and control windows for self-controlled tree-temporal tree-based scan statistics analysis.
A broad assessment of rotavirus vaccine safety in infants in Korea: Insights from a data-driven signal detection approach
  • Article
  • Full-text available

February 2025

In light of the widespread use of rotavirus vaccines, there is a pressing need to perform thorough, large-scale surveillance to actively monitor safety. This study aimed to identify potential adverse events following rotavirus vaccination in infants. Using a nationwide linked database of the national immunization registry and health insurance claims data, we identified infants vaccinated with the first dose of rotavirus vaccine between January 2016 and October 2022. The self-controlled tree‐temporal scan statistics method analyzed all incident diagnoses recorded within 56 days post-vaccination and evaluated all temporal risk windows. Among 1,720,778 rotavirus vaccine recipients 64,752 infants contributed to the analysis, yielding 72,970 incident diagnoses. Of these, 28 clusters were categorized as known adverse drug reactions (ADRs), including infection following immunization (Days 1–2, p<.001), viral infection (Days 1–5, p<.001), urticaria and erythema (Days 3–9, p<.001), acute upper respiratory infections (Days 28–42, p<.001), and pneumonia (Days 9–19 or 28–42, p<.001). Seventeen clusters were classified as ADR-related events, such as the ones clinically related to ADR or lower-level diagnostic codes of ADR. The remaining 26 clusters were classified as signals, including sepsis (Days 1–20, p<.001), meningitis (Days 1–23, p<.001), liver disease (Days 4–11, p<.001), and tubulo-interstitial nephritis (Days 11–38, p<.001). A cluster of intussusceptions was only found in monovalent vaccine-stratified analysis (Days 5–8, p = 0.005). This study confirmed known ADRs following rotavirus vaccination, while identifying potential safety signals requiring further investigation. These findings emphasize the importance of active vaccine surveillance and underscore the need for epidemiological studies with validated outcome definitions to confirm causal relationships between rotavirus vaccination and the detected outcomes.


PRISMA 2020 study flow diagram.
Umbrella review of the safety of Chikungunya vaccine platforms used in other vaccines

Chikungunya virus (CHIKV), transmitted through Aedes mosquitoes, is a significant global health concern. Various vaccine platforms have been explored to combat CHIKV, including formalin inactivation, live-attenuated strains, virus-like particles (VLPs), viral vectors, and mRNA technologies. This umbrella review synthesizes evidence on the safety profiles of vaccine platforms used in Chikungunya vaccines that have been applied in other vaccines, focusing on adverse events of special interest (AESI) in pregnant persons, children, and adolescents. A comprehensive overview of systematic reviews (SRs) was conducted. Results: Seven systematic reviews were included and complemented with primary studies. Vaccines like influenza, human papillomavirus (HPV), and COVID-19, which share platforms with Chikungunya vaccines, showed no significant increase in AESI. Moderate-to high-quality SRs supported favorable safety profiles. Vaccines sharing platforms with Chikungunya vaccines generally exhibit acceptable safety profiles in pregnant persons, children, and adolescents.



The reported incidence of pertussis in the whole population and children under five years in Chongqing from 2019 to 2023.
Monthly distribution of reported pertussis cases in children under 5 years in Chongqing, from 2019 to 2023.
Regional distribution of pertussis cases in children under 5 years in Chongqing from 2019 to 2023.
Cumulative risk curve of incidence interval after vaccination with DTaP of different doses.
Pertussis epidemiological surveillance and immunization history in children under five years in a megacity in China from 2019 to 2023

February 2025

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11 Reads

To analyze the epidemiological characteristics and influencing factors of pertussis in children under five years in Chongqing from 2019 to 2023, providing scientific evidence for further prevention and control. The epidemiological characteristics of pertussis cases in children under five years and vaccination history with pertussis-containing vaccines were described, and the influencing factors and cumulative risk of disease onset after vaccination were analyzed using the Cox proportional hazards regression model. From 2019 to 2023, a total of 4,135 pertussis cases were reported in children under five years in Chongqing, with cases occurring predominantly between April and August. Infants under 1 year accounted for the highest proportion of cases at 66.82% (2,763/4,135); the annual reported incidence was higher in boys (141.26/100,000) than in girls (122.09/100,000). Over half of the cases, 59.78% (2,472/4,135) had received at least one dose of a pertussis-containing vaccine, and there were significant differences in vaccination history among different age groups (χ² = 483.248, p < .01). Cox’s regression analysis indicated that the total number of doses received (p < .01) was an influencing factor for the interval between vaccination and disease onset. The hazard ratios (HRs) for three doses, two doses, and one dose were 0.182 (95% CI: 0.138–0.241), 0.485 (95% CI: 0.359–0.654), and 0.315 (95% CI: 0.233–0.425). Young children, including infants and preschool-aged children, were still a high-risk group for pertussis infection in Chongqing. It is recommended to administer an additional dose of Diphtheria-Tetanus-Pertussis vaccine (DTaP) vaccine to preschool children aged four to six in China.


Pneumococcal vaccination rates from (a) immunization registry records of residents (n = 42), (b) managing directors’ recall when no records were available (n = 242), and (c) overall from immunization records, managing directors’ recall when no records were available and from facilities (n = 86) with a response of “no vaccination” (n = 370).
Willingness to recommend pneumococcal, influenza, and COVID-19 vaccines by the managing directors (n = 445).
Source of information about the pneumococcal vaccine (Yes, n = 78; No, n = 39; neutral, n = 299).
Forest plot for subgroup analysis based on a multivariable logistic model including factors associated with high pneumococcal vaccination (≥15%) in elderly care facilities (N = 365) *1.
Pneumococcal vaccination in elderly care facilities in Japan: A cross-sectional, web-based survey

February 2025

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This study evaluated pneumococcal vaccination status using evaluable data collected from 445 of 1,313 managing directors of elderly care facilities in Japan through an online survey (September 5, 2022-November 25, 2022; UMIN000048747); comparisons were made with the influenza (2021–2022 vaccination only) and coronavirus disease 2019 (COVID-19) vaccination status. Among facilities who kept pneumococcal vaccination records (n = 42), the mean pneumococcal vaccination rate was 31.1%, with the rate being higher for the influenza (93.1%; n = 234) and COVID-19 (94.3%; n = 285) vaccines. Overall, excluding facilities that answered that the corresponding vaccine status at their sites was unknown, the percentage of facilities with high vaccination rates (80% to 100%) was substantially higher for the influenza (80.5%; 351/436) and COVID-19 (89.6%; 396/442) vaccines than for the pneumococcal vaccine (6.5%; 24/370). Multivariable analysis showed that major factors associated with a high pneumococcal vaccination rate (≥15%) were “managing director’s willingness to recommend” and “pneumococcal vaccination request from the residents.” The most common reason for their willingness to recommend the pneumococcal vaccine was that it is an effective disease prevention strategy (83.3%; 65/78) and for their unwillingness to recommend the pneumococcal vaccine was the inability to understand the effectiveness of the vaccine (43.6%; 17/39). In conclusion, there is a need to improve pneumococcal vaccination rates in elderly care facilities in Japan. Strategies such as increasing awareness and encouraging pneumococcal vaccine recommendation among managing directors, especially for residents not eligible for the national subsidy program, and providing regular training on the pneumococcal vaccine for staff and residents are required.


“The big topic is COVID”: A qualitative study about changes in HPV vaccine conversations between parents and primary care team members throughout the COVID-19 pandemic

February 2025

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3 Reads

Pandemic-related disruptions in primary care delayed important discussions between providers and parents about routine vaccinations. Conversations have become even more challenging since the COVID-19 pandemic due to increased vaccine hesitancy. This qualitative study explored changes in human papillomavirus (HPV) vaccine conversations within the context of the pandemic from the perspective of primary care team members (PCTMs). Twenty-five PCTMs serving children between 9 and 17 y old in Pennsylvania during the pandemic were conveniently sampled. PCTMs rated their confidence and agreement related to HPV vaccine conversations and pandemic impact. Semi-structured interview questions assessed changes in their HPV vaccine conversations throughout the pandemic. Open-ended questions inquired about PCTMs’ thoughts on the COVID-19 pandemic and if or how it impacted HPV vaccination uptake in their practice. Data were collected from May to July 2024. Verbatim transcriptions were analyzed using both inductive and deductive approaches to thematic analysis. Participants were 44% pediatricians, 50% had ≥20 y experience, and 68% were White. Six themes emerged: (1) parents show a range of reactions about HPV vaccination; (2) disruptions in healthcare visits and heightened parental concerns impede vaccination; (3) PCTMs notice clear changes in vaccine acceptance rates; (4) reasons for vaccination refusal have not substantially changed as a result of the pandemic; (5) importance of interpersonal relationships with parents; and (6) PCTM burnout impacts conversations. The pandemic added challenges to HPV vaccine conversations with parents. Findings from this study can be used to refine existing communication approaches to improve HPV vaccine conversations in primary care.


Profile of Chlamydia vaccine research: A bibliometric analysis

Vaccination is the most effective measure to prevent Chlamydia infection. However, to date, no vaccine has successfully completed the rigorous clinical trial process and gained regulatory approval for use in clinical practice. Scholars have been working on a safe and effective Chlamydia vaccine. In order to better grasp, the global frontiers and development trends in this field, a comprehensive bibliometric analysis was carried out. A total of 234 publications closely regarding Chlamydia vaccines were culled from the Web of Science Core Collection database, and the bibliometric information was then extracted with CiteSpace and VOSviewer software. After measurement analysis, the most influential papers were identified in this area, including highly cited papers, references with strong citation burst, and high co-citated papers. Vaccine has published the most literature on Chlamydia vaccines. Only scholars from 39 countries/regions have been engaged in studying Chlamydia vaccines. The USA is the most prolific country and has the highest collaborative strength. The current research area has focused on protective immunity and immunopathological response. Major outer membrane protein (MOMP) is the most common target vaccine antigen. This study reveals the status of literature and highlights emerging trends in this field, which helps researchers seek insights into this area and serve as a reference guide for further investigations.


Recent advances in immunotherapy targeting CETP proteins for atherosclerosis prevention

Cholesteryl ester transfer protein (CETP) plays a key role in lipoprotein metabolism, and its activity has been linked to the risk of atherosclerosis (AS). CETP inhibitors, such as obicetrapib, represent a novel approach in immunotherapy to reduce the risk of atherosclerotic cardiovascular disease (ASCVD) by targeting lipid metabolism. In addition, CETP vaccines are being explored as a novel strategy for the prevention and treatment of ASCVD by inducing the body to produce antibodies against CETP, which is expected to reduce CETP activity, thereby increasing high-density lipoproteins (HDL) levels. This paper provides a comprehensive overview of the structure of CETP, the mechanisms of lipid transfer and the progress of immunotherapy in the last decade, which provides possible ideas for future development of novel drugs and optimization of immunization strategies.


PRISMA flow chart of study selection process for studies included in the systematic review.
Comparison of yearly number of included studies based on different methods in China. This dumbbell chart depicted the publication year and number of included studies based on CVM and DCE methods. The pink dots represented the number of studies based on CVM, and the blue dots represented the number of studies based on DCE. In 2020, the same number of studies were published based on both methods.
Plots of trace and density of MCMC. This group of figures reported the convergence of MCMC sampling for WTP of vaccines. Taking the influenza vaccine as an example, from top to bottom, the first three graphs were trace plots of the parameters; the latter three were density plots of the parameters.
Plots of joint posterior density. This group of joint posterior density plots reported the results of sensitivity analysis for the effect parameter and heterogeneity parameter based on DIRECT.
Willingness to pay for vaccines in China: A systematic review and single-arm Bayesian meta-analysis

The effective implementation of vaccination heavily depends on the society’s willingness to pay (WTP). There is currently a dearth of comprehensive evidence about WTP for vaccines in China. This systematic review aims to review studies on the WTP for vaccines, to summarize factors affect WTP in China. Base-case analysis and Sensitivity analysis of WTP for every vaccine were estimated via single-arm Bayesian meta-analysis. A total of 28 studies were included for systematic review. The point estimates and 95% Credible Interval of pooled WTP for influenza and HPV (9-valent) vaccine were 27.409(23.230,31.486),27.409 (23.230, 31.486), 464.707 (441.355, 489.456). Influencing factors to WTP were age, income, peer influence, health condition and etc. Future research should give focus to improving sample representativeness and survey tool, conducting intervention trials, identifying effective methods to promote WTP.


PfCSP-ferritin nanoparticle malaria vaccine antigen formulated with aluminum-salt and CpG 1018® adjuvants: Preformulation characterization, antigen-adjuvant interactions, and mouse immunogenicity studies

February 2025

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13 Reads

Circumsporozite protein (CSP), the most abundant surface protein in parasitic Plasmodium falciparum (Pf) sporozoite and an attractive target for malaria vaccine design, has been shown to induce protective humoral response in humans. In this work, we characterized and formulated a promising recombinant PfCSP immunogen (155) candidate consisting of two PfCSP epitopes (i.e. junction, NANP repeat) fused to H. pylori apoferritin forming a 24-mer nanoparticle. In addition, two N-linked glycans were engineered to mitigate possible anti-apoferritin immune responses, and a universal T-cell epitope was included to further enhance immunogenicity. Physicochemical characterization of the 155 antigen was performed including primary structure, post-translational modifications, conformational stability, and particle size. A competitive ELISA was developed to assess antigen binding to a PfCSP-specific mAb. The in vitro antigenicity of the 155 antigen was measured upon formulation with adjuvants, including aluminum-salts (i.e. AlhydrogelTM, Adju-PhosTM) and the TLR-9 agonist CpG 1018®, when freshly combined and after storage at different temperatures over 3 months. The in vivo immunological impact of various adjuvanted formulations of the 155 antigen was investigated in mice. The results support the formulation of 155 with AlhydrogelTM + CpG 1018® adjuvants as a promising recombinant malaria vaccine candidate from both a pharmaceutical and immunological perspective.


Research trends of neoadjuvant therapy for breast cancer: A bibliometric analysis

February 2025

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11 Reads

The approach of neoadjuvant therapy for breast cancer, which involves administering systemic treatment prior to primary surgery, has undergone substantial advancements in recent decades. This strategy is intended to reduce tumor size, thereby enabling less invasive surgical procedures and enhancing patient outcomes. This study presents a comprehensive bibliometric analysis of research trends in neoadjuvant therapy for breast cancer from 2009 to 2024. Using data extracted from the Web of Science Core Collection, a total of 3,674 articles were analyzed to map the research landscape in this field. The analysis reveals a steady increase in publication output, peaking in 2022, with the United States and China identified as the leading contributors. Key institutions, such as the University of Texas System and MD Anderson Cancer Center, have been instrumental in advancing the research on neoadjuvant therapy. The study also highlights the contributions of influential authors like Sibylle Loibl and Gunter von Minckwitz, as well as major journals such as the Journal of Clinical Oncology. Emerging research topics, including immunotherapy, liquid biopsy, and artificial intelligence, are gaining prominence and represent potential future directions for clinical applications. This bibliometric analysis provides critical insights into global research trends, key contributors, and future developments in the field of neoadjuvant therapy for breast cancer, offering a foundation for future research and clinical practice advancements.


Flow diagram of COVERED participants included in this analysis.
Number of respondents in each category of the WHO vaccine hesitancy scale – perceived vaccine risks.
Number of respondents in each category of the theory of planned behavior – attitudes toward COVID-19 vaccines.
Number of respondents in each category of the perceived reliability of healthcare information sources.
Acceptance and attitudes towards COVID-19 vaccination during pregnancy in Canada

February 2025

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19 Reads

The COVID-19 pandemic posed a unique set of risks to pregnant women and pregnant people. SARS-CoV-2 infection in pregnancy is associated with increased risk of severe illness and adverse perinatal outcomes. However, evidence regarding the use of COVID-19 vaccines in pregnancy shows safety and efficacy. Despite eligibility and recommendations for COVID-19 vaccination among pregnant women and pregnant people in Canada, uptake remains lower compared to the general population, warranting exploration of influencing factors. The COVERED study, a national prospective cohort, utilized web-based surveys to collect data from pregnant women and pregnant people across Canada on COVID-19 vaccine attitudes, uptake, and hesitancy factors from July 2021 to December 2023. Survey questions were informed by validated tools including the WHO Vaccine Hesitancy Scale (VHS) and the Theory of Planned Behavior (TPB). Of 1093 respondents who were pregnant at the time of the survey, 87.7% received or intended to receive a COVID-19 vaccine during pregnancy. TPB variables such as positive attitudes toward COVID-19 vaccines (OR = 1.11, 95% CI = 1.08–1.14), direct social norms, and indirect social norms were significantly associated with vaccine acceptance. Perceived vaccine risks, assessed by the WHO VHS, were greater in those not accepting of the vaccine. Our study identified several key factors that play a role in vaccine uptake: perceived vaccine risks and safety and social norms. These findings may guide public health recommendations and prenatal vaccine counseling strategies.


Flow of screening, randomization and participants disposition.
Immunogenicity and safety of a live attenuated varicella vaccine in children aged 1 to 12 years: A double-blind, randomized, parallel-controlled phase III clinical trial in China

February 2025

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3 Reads

Chickenpox outbreaks frequently occur in collective settings such as kindergartens and schools, posing a significant threat to children’s physical and mental health. This study aimed to evaluate the immunogenicity and safety of the freeze-dried live attenuated varicella vaccine (VarV) developed by Beijing Minhai Biotechnology Co. LTD. in healthy participants aged 1–12 years. In this phase III, single-center, randomized, double-blind, active-controlled trial,1,200 healthy participants randomly assigned in a 1:1 ratio to receive one dose of either the test vaccine or the active control vaccine. Venous blood samples were collected before vaccination and 42 days after vaccination, and the fluorescent antibody to membrane antigen (FAMA) assay was used to detect VZV antibody. Adverse events (AEs) observed within 42 days after vaccination and serious adverse events (SAEs) within six months after vaccination were recorded. The seroconversion rates in the test and control groups were 96.79% and 96.43%, respectively, with a difference of 0.36% (95% CI, −1.76%–2.48%). The geometric mean titers (GMTs) were 61.74 and 58.04, respectively, with a difference of 1.06 (95% CI, 0.92–1.23). The lower limits of the 95% CI for the differences in seroconversion rates and GMT ratios between the two groups were greater than their respective pre-set non-inferiority margins. The overall incidence of AEs (p = .0112) in the test group was significantly lower than that in the control group. The freeze-dried live attenuated VarV developed by Beijing Minhai Biotechnology Co. LTD. demonstrated good immunogenicity and higher safety compared to the active control vaccine in healthy participants aged 1–12 years.


Adverse events following immunization surveillance on two types of enterovirus 71 vaccines: A real-world comparative study in China

February 2025

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4 Reads

To comprehensively assess the safety and difference of two types of EV71 vaccines: EV71-Vero, produced using Vero cells and EV71-H2, using human diploid cells. Our research included children of the recommended age who voluntarily received the EV71 vaccine in Hebei Province from 2019 to 2023. Detailed data on adverse events following immunization (AEFI) were collected, analyzed and compared for EV71-Vero and EV71-H2 vaccines. With 477 AEFI reported, the reported rate was 14.21 per 100,000 doses. Most cases occurred in infants under one year of age (45.91%). No significant differences in the AEFI reported rate were found between two types of EV71 vaccines across various demographic. However, a higher number of AEFI was reported in children under 1-year old following EV71-Vero compared to EV71-H2 with a reversal in 4–5 years- group (χ² = 13.90, p = .01). The prognosis of cured took higher proportion for EV71-Vero than for EV71-H2 while inversely with improved outcome. The EV71 vaccine is advisable recommend to the appropriate age children to prevent EV7l infection. Both the EV71-Vero and EV71-H2 vaccines have good safety profiles. The reported AEFI, primarily high fever and allergic reactions, showed no significant differences in reported rates or case characteristics between the two types.


Immune checkpoint inhibitors in cancer patients with autoimmune disease: Safety and efficacy

The utilization of immune-checkpoint inhibitors (ICIs) in cancer immunotherapy frequently leads to the occurrence of immune-related adverse events (irAEs), making it generally not recommended for patients with preexisting autoimmune diseases. Hence, we conducted a meta-analysis on safety and efficacy of ICIs in cancer patients with preexisting autoimmune diseases to provide further insights. PubMed, EMBASE, and Cochrane Library were systematically searched until December 20, 2024. The main summary measures used were pooled rate and risk ratio (RR) with 95% confidential interval (CI), which were analyzed using R statistic software. A total of 52 articles were included in the study. When cancer patients with preexisting autoimmune diseases received ICIs treatment, the overall incidence was 0.610 (95% CI: 0.531–0.686) for any grade irAEs, 0.295 (95% CI: 0.248–0.343) for flares, 0.325 (95% CI: 0.258–0.396) for de novo irAEs, 0.238 (95% CI: 0.174–0.309) for grade ≥3 irAEs, and 0.143 (95% CI: 0.109–0.180) for discontinuation due to immunotoxicity. Compared with those without autoimmune diseases, cancer patients with autoimmune diseases experienced a higher risk of any-grade irAEs (RR: 1.23, 95% CI: 1.12–1.35) and discontinuation due to immunotoxicity (1.40, 95% CI: 1.11–1.78). However, no statistically significant differences were observed in the incidence of grade ≥3 irAEs, objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) between the two groups. During ICIs treatment, irAEs are common among cancer patients with autoimmune diseases, but severe irAEs is relatively low. ICIs are effective in this population, but should be strictly monitored when used to avoid immunotoxicity.


Expression profile of main ARs across immune cell subsets in TME. This heatmap depicts the differential expression levels of A1R, A2AR, A2BR, and A3R across various immune cell populations implicated in the TME. Immune cell types include DCs, Th cells, macrophages, NK cells, granulocytes, mast cells, eosinophils, basophils, monocytes, platelets, and ILCs. The data suggest prominent expression of A2AR on DCs, Th cells, and macrophages, highlighting its potential role in modulating immune responses within the TME. This comprehensive analysis provides insights into the distribution of A2AR across immune cell subsets, underscoring its significance as a potential target for cancer immunotherapy. The data presented in this figure are derived from extensive genomic analyses, incorporating datasets from the cancer genome atlas (TCGA).²⁷
The A2AR signaling within the TME. The generation and modulation of extracellular adenosine accentuate its multifaceted role in shaping the TME. This intricate interplay, orchestrated by the A2AR signaling, involves diverse immune cell subsets within the TME, including dendritic cells (DCs), regulatory T cells (Tregs), effector T cells (Teffs), natural killer (NK) cells, tumor-associated macrophages (TAMs), and myeloid-derived suppressor cells (MDSCs). This signaling axis shapes the dynamics of tumor immune evasion and progression at both cellular and molecular levels. Furthermore, A2AR activation extends its influence beyond immune cells to nonimmune components of the TME, including tumor cells and stromal cells, impacting processes like epithelial-mesenchymal transition and contributing to tumor progression.
Schematic of neo-antigen mRNA-LNPs+A2ARi vaccines architecture. This diagram shows neo-antigen mRNA-loaded lipid nanoparticles (LNPs) conjugated with A2A receptor inhibitors (A2ARi). it highlights how A2ARi is attached to the LNPs for targeted delivery to dendritic cells expressing A2AR. The lipid-based core of the LNPs encapsulates the neo-antigen mRNA payload, and various A2ARi types are compatible with this delivery system.
Enhanced cancer immunotherapy through neo-antigen mRNA-LNPs+A2ARi. A2ARi, linked to LNPs, enables targeted delivery to A2AR-expressing dendritic cells (DCs) and reduces the DCs migrating in TME. This delivery enhances neo-antigen presentation on MHC class I molecules, priming cytotoxic T lymphocytes (CTLs) for cancer cell destruction. Additionally, A2ARi on DCs alleviate ad-mediated immunosuppression, promoting CTL activation. Enhanced mRNA neo-antigens with A2AR ligands enhance uptake by other immune cells, such as macrophages and natural killer cells, amplifying the anti-tumor immune response. mRNA-LNPs+A2ARi vaccines facilitate robust endogenous neo-antigen presentation and CTL activation through this dual mechanism.
Neoantigen mRNA vaccines and A2A receptor antagonism: A strategy to enhance T cell immunity

Although neo-antigen mRNA vaccines are promising for personalized cancer therapy, their effectiveness is often limited by the immunosuppressive tumor microenvironment (TME). The adenosine A2A receptor (A2AR) inhibits dendritic cell (DC) function and weakens antitumor T cell responses through hypoxia-driven mechanisms within the TME. This review explores a novel strategy combining neo-antigen mRNA vaccines with A2AR antagonists (A2ARi). By targeting A2AR, this approach reduces TME-induced immunosuppression, enhances DC activation, and improves neo-antigen presentation. The review also discusses lipid nanoparticles (LNPs) to co-deliver A2ARi and mRNA vaccines, optimizing their effectiveness. The integration of neo-antigen mRNA-LNPs with A2ARi modulation offers a promising strategy to overcome immunosuppression, stimulate DC activation, and achieve precise anti-tumor responses with minimal off-target effects. This synergy represents significant progress in cancer immunotherapy, advancing the potential for personalized neoantigen therapies.


Consort diagram for study enrollment.
Effectiveness of inactivated influenza vaccine against laboratory-confirmed influenza in elderly Chinese patients with diabetes: A test-negative design case-control study

January 2025

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3 Reads

Vaccination coverage for influenza among diabetic populations remains suboptimal. Various factors contribute to this low vaccination rate, with a prominent issue being skepticism among potential vaccine recipients regarding vaccine effectiveness. We conducted a retrospective test-negative case-control study among diabetic patients aged 60 years and older in Ningbo, Zhejiang Province, China, spanning for four influenza seasons from 2018–19 to 2021–22. A total of 2,204 elderly patients were tested for influenza virus nucleic acid or antigen during the study period. After applying exclusion criteria, 199 influenza-positive cases and 199 matched influenza-negative controls were included in the final analysis. Vaccine effectiveness (VE) was estimated using an unconditional multiple logistic regression model, adjusted for age, gender, household registration and underlying health status. VE was calculated as (1-odds ratio(OR)) × 100%. Overall, the adjusted VE against laboratory-confirmed influenza from inactivated influenza vaccines over the study period was 59.4% (95%CI, 36.3% to 74.4%). VE varied across seasons, with the highest observed in the 2020–21 season and the lowest in the 2019–20 season. Importantly, repeated vaccination did not diminish vaccine effectiveness (OR = 1.2; 95% CI: 0.6 to 2.5). These findings provide a robust basis for recommending annual influenza vaccination among all elderly individuals with diabetes, absent any known contraindications.


Development history of pneumococcal vaccines in China.
Number of lot releases of different types of pneumococcal vaccines in China, 2013–2023. The proportion of imported PPV23 in the total PPV23 supply ranged from 2.8% to 61.8% during 2013–2023, with the ratio being 13.9% in 2022 and 18.6% in 2023. For PCV13, the proportion of imported products decreased from 100% in 2017 to 9.72% in 2023.
Pneumococcal vaccines in China

Invasive pneumococcal disease (IPD) is a serious global public health problem and the leading cause of morbidity and mortality in children and adults in China. Thus, developing and administering pneumococcal vaccines are important for disease prevention. The PPV23 and PCV13 vaccines are available in the Chinese market and are primarily produced by domestic manufacturers. The potential risk of increased IPD caused by non-vaccine serotypes should be considered. Here, we review the current status of IPD, pneumococcal vaccines, and their quality control in China. We also address the challenges and future directions for making progress in controlling IPD, emphasizing the need for further evaluation of the disease burden and monitoring the effectiveness of vaccination efforts.


Opportunities and challenges of immuno-oncology: A bibliometric analysis from 2014 to 2023

The emergence of immuno-oncology (IO) has led to revolutionary changes in the field of cancer treatment. Despite notable advancements in this field, a thorough exploration of its full depth and extent has yet to be performed. This study provides a comprehensive overview of publications pertaining to IO. Publications on IO from 2014 to 2023 were retrieved by searching the Web of Science Core Collection database (WoSCC). VOSviewer software and Citespace software were used for the visualized analysis. A total of 1,874 articles have been published in the IO domain. The number of publications and citations has been increasing annually. This study also examines the primary research directions within the field of IO. In conclusion, this study offers a comprehensive overview of the opportunities and challenges associated with IO, illuminating the current status of research and indicating potential future trajectories in this rapidly progressing field. This study provides a comprehensive survey of the current research status and hot spots within the field of IO. It will assist researchers in comprehending the current research emphasis and development trends in this field and offers guidance for future research directions.


Schematic overview of mechanisms of resistance to HER2-targeted therapy.
Discussion on the mechanism of HER2 resistance in esophagogastric junction and gastric cancer in the era of immunotherapy

Human epidermal growth factor receptor 2 (HER2) is a critical biomarker and therapeutic target in gastric/gastroesophageal junction (G/GEJ) cancers, despite the initial success of HER2-targeted therapies, such as trastuzumab, resistance to these drugs has emerged as a major impediment to effective long-term treatment. This review examines the mechanisms of drug resistance in HER2-positive G/GEJ cancer, the primary mechanisms of resistance explored include alterations in the HER2 receptor itself, such as mutations and changes in expression levels, as well as downstream signaling pathways, and interactions with the tumor microenvironment (TME). Furthermore, the review discusses the Novel therapeutic approaches, including the use of antibody-drug conjugates (ADCs) and combination therapies are assessed for their potential to enhance outcomes. By integrating recent research findings and clinical trials, this review aims to provide oncologists and researchers with insights into developing more effective treatments for patients with drug-resistant HER2-positive G/GEJ cancer.


US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study population (2015–2016, 2016–2017, 2017–2018, and 2019–2020).
Vaccine effectiveness against influenza-associated hospitalization among adults with and without liver disease, stratified by age group.
Vaccine effectiveness against influenza-associated hospitalizations in adults with liver disease, 2015–2020: US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN)

January 2025

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7 Reads

Influenza causes 100,000–710,000 hospitalizations annually in the U.S. Patients with liver disease are at higher risk of severe outcomes following influenza infection. This study evaluated influenza vaccine effectiveness (VE) against influenza-associated hospitalization among adults with liver disease. Data from the U.S. Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN), a test-negative case-control study, from 2015 to 2020 were used to estimate VE among adults ≥18 years admitted for acute respiratory illness. VE was calculated as (1-adjusted odds ratio)*100%, comparing the odds of vaccine receipt between laboratory-confirmed influenza cases and test-negative controls using multiple logistic regression with inverse probability of treatment weighting (IPTW). In total, 1,622 (12.8%) of 12,704 adults had ≥1 liver disease(s). Compared with those without liver disease, adults with liver disease were more likely to be admitted to the intensive care unit (15.7% vs 12.8%, p = .001) or to die in hospital (3.0% vs 1.4%, p < .001). The IPTW-adjusted VE against influenza-associated hospitalization was 27% (95% confidence interval [CI], 22–32%) among patients without liver disease, but the VE of 11% (95% CI, −8–26%) was not significant among those with liver disease. Significant effect modification of VE by the presence of liver disease was found (p < .05 for interaction term). While influenza vaccination significantly reduced the risk of influenza-associated hospitalization among adults without liver disease, the protective effect was not significant among those with liver disease. Further studies are warranted to evaluate influenza VE in patients with different types of liver disease and with specific vaccine formulations.


The bibliometrics analysis of DNA vaccine. (a) The trend of annual publication number and citation frequency of articles in this research field. It shows the number of publications and cited times every year. (b) The fitting equation of annual publication volume. The fitting curve (Y = −22.52*X + 45,791, R² = 0.83, p = .0002) shows that there is a strong linear relationship between the year and the number of publications. The co-occurrence map of countries (c), institutions (d) and journals (e) about the research field. The visualization map of authors (f) co-cited authors (g) about the research field (note: minimum number of articles of an author ≥ 7; minimum number of citations of an author ≥ 80). The co-occurrence density map (h) of keywords (note: minimum number of occurrences of keywords ≥ 70). (i) The network visualization of keywords. Each node in the graph represents a separate individual, such as a country, institution, author, or keyword, and the size of the node indicates the frequency of that occurrence. Connecting lines indicate co-occurrence relationships between keywords.
The timeline viewer of keywords. It illustrates the progression of keywords in DNA vaccine research from 2014 to 2024. Each node within the figure denotes a specific keyword, with the node’s size corresponding to the frequency of the keyword’s occurrence in a given year. The connecting lines signify co-occurrence relationships between keywords, indicating the frequency with which these concepts are concurrently discussed in scholarly papers. The color gradient represents the passage of time, transitioning from lighter shades in 2014 to darker shades in 2024. This visualization allows for the observation of shifts in research focus and the emergence of new trends within the field.
Top 50 references with the strongest citation bursts in this field. It shows the top 50 references with the strongest citation bursts in the field of DNA vaccine research from 2014 to 2024. Each line in this part of the figure represents a document, detailing its publication information, year of publication, burst intensity, and the duration of the burst. This enables a clear identification of pivotal research findings that have garnered substantial attention and frequent citation in the domain of DNA vaccine research during this timeframe.
Global research hotspots and trends in DNA vaccine research: A bibliometric and visualization study from 2014 to 2024

January 2025

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11 Reads

This bibliometric and visualization study provides a comprehensive analysis of global research hotspots and trends in DNA vaccine research from 2014 to 2024. By employing data sourced from the Web of Science Core Collection, we identified a total of 3,600 articles. Our analysis reveals a declining trend in annual publications. Active countries, institutions, journals, and authors were identified, with China, the Pasteur Network, the Vaccine Journal, and David B Weiner being the most prolific contributors. Keywords cluster analysis distinguished four major research directions: infectious disease and immunity, viral challenge and vaccine development, optimization of DNA vaccine delivery systems, and cancer and immunotherapy research. The literature co-citation analysis revealed four major research hotspots, including DNA vaccines for Zika virus, human papillomavirus (HPV), and COVID-19, as well as safety, efficacy, and immunogenicity studies of DNA vaccines. Concurrently, the burst citation analysis identified emerging themes, including the development of DNA vaccines for COVID-19, Ebola, and MERS-CoV, as well as innovations in antigen design and delivery technologies. This study offers valuable insights into the evolution and future directions of DNA vaccine research, emphasizing its importance for global public health and the potential to address current and future health challenges.


Safety and immunogenicity of Ad26.COV2.S in adolescents: Phase 2 randomized clinical trial

January 2025

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3 Reads

We conducted a randomized, Phase 2 trial to assess the safety and humoral immunogenicity of reduced doses/dose volume of the standard dose of Ad26.COV2.S COVID-19 vaccine (5 × 10¹⁰ viral particles [vp]) in healthy adolescents aged 12–17 years. Participants were randomly assigned to receive Ad26.COV2.S at reduced dose levels of 0.625 × 10¹⁰ (0.5 mL), 1.25 × 10¹⁰ (0.5 mL) or 2.5 × 10¹⁰ (0.5 mL or low volume 0.25 mL) vp in a 1- or 2-dose (56-day interval) primary schedule. Adolescents who received a 1-dose primary schedule received a 2.5 × 10¹⁰ vp booster dose 6 months later. Safety and humoral immunogenicity were assessed up to 6 months post-last vaccination. All regimens were well tolerated, with no safety concerns identified. Local and systemic solicited AEs in adolescents were consistent with the known safety profile in adults. All 1- and 2-dose Ad26.COV2.S primary schedules elicited robust peak Spike-binding antibody responses and virus neutralizing titers against the reference strain, in participants with and without preexisting SARS-CoV-2 immunity. Immune responses were durable for at least 6 months. Spike-binding antibody responses were comparable to those elicited in young adults aged 18–25 years who received a standard dose of Ad26.COV2.S in Phase 3 efficacy studies Reduced doses/dose volume of Ad26.COV2.S had an acceptable safety profile and elicited robust humoral immune responses in adolescents aged 12–17 years. All 1- and 2-dose schedules elicited Spike-binding antibody responses that were comparable to an adult population in whom efficacy has been demonstrated using a higher vaccine dose. (clinicaltrials.gov NCT05007080).


Journal metrics


4.1 (2023)

Journal Impact Factor™


7.9 (2023)

CiteScore™


0.897 (2023)

SNIP


0.927 (2023)

SJR

Editors