Human Vaccines & Immunotherapeutics

Nano-enhanced immunity: A bibliometric analysis of nanoparticles in vaccine adjuvant research
Elhassan Taha MM, Abdelwahab SI, Moni SS, Farasani A, Aljahdali IA, Oraibi B, Alfaifi HA, Alzahrani AH and Ali Jerah A
This study analyzed the growth, collaboration, citation trends, and emerging topics in nanoparticle-based vaccine and adjuvant research (NVAR) from 1977 to 2023, using data from the Scopus database. The field showed a steady growth rate of 7.53% per year. Leading researchers Jaafari, M.R. and Alving, C.R. contributed significantly to the field, with 24.22% of publications and 38.92% of total citations coming from the United States. International collaboration was very strong, particularly between the US, UK, Germany, China, and France. Key research topics include nanoparticles, immunotherapy, COVID-19, and vaccines with a focus on SARS-CoV-2 and malaria. Emerging topics include vaccine adjuvants, mRNA, and neutralizing antibodies. This study emphasizes the importance of ongoing collaboration and interdisciplinary efforts to advance the field of NVAR.
Impact of propensity to COVID-19 vaccination/vaccine on influenza vaccination from willingness to behavior among older adults in rural China
Zhang SS, Shi W, Du J, Zhang WX, Yuan M, Zhou Y, Wang L, Zhao T, Ma QY, Zhang S, Yang H, Zhang X, Wang M, Huang N, Zeng J, Liu Y, Zhang Y, Cui F and Lu QB
To explore impact of the propensity to coronavirus disease 2019 (COVID-19) vaccine/vaccination on influenza vaccination from willingness to behavior after COVID-19 pandemic among older adults in rural China. A combined study involving a cross-sectional survey for the willingness of influenza vaccination, a health education momentary intervention and a community intervention program were conducted from September 11 to 16, 2023 among rural older adults in China. Totally 3138 individuals were investigated in this study with 1923 (61.3%) willing to receive influenza vaccination. After the momentary intervention, 47.8% (582/1215) individuals changed to be willing to receive influenza vaccination. There were 1440 (78.8%) vaccinated. The influenza vaccination willingness rate was significantly higher in the participants willing to receive COVID-19 vaccine booster dose vaccination than the participants unwilling to (69.4% . 37.7%, adjusted OR [aOR] = 2.671, 95% CI 2.211-3.227,  < .001), as well as for the influenza vaccination willingness change rate (52.2% . 41.7%, aOR = 1.303, 95% CI 1.022-1.662,  < .05) and the influenza vaccination behavior rate (79.7% . 74.9%, aOR = 1.337, 95% CI 1.002-1.784,  < .05). The influenza vaccination behavior rate was significantly higher in those positive toward COVID-19 vaccine effectiveness or safety overall (80.0% . 74.9%, aOR = 1.394, 95% CI 1.065-1.823; 80.6% . 70.9%, aOR = 1.850, 95% CI 1.395-2.454; both  < .05). There was a positive impact of COVID-19 vaccine/vaccination on influenza vaccination from willingness to behavior among the older adults in rural China after COVID-19 pandemic, suggesting that integrating health education of related pathogens and vaccines might promote influenza vaccination.
Substantial reduction in the clinical and economic burden of disease following variant-adapted mRNA COVID-19 vaccines in immunocompromised patients in France
Lee A, Davido B, Beck E, Demont C, Joshi K, Kohli M, Maschio M, Uhart M and El Mouaddin N
An evaluation was conducted to predict the economic and clinical burden of vaccinating all immunocompromised (IC) individuals aged ≥30 years with mRNA-1273 variant-adapted COVID-19 vaccines versus BNT162b2 variant-adapted vaccines in Fall 2023 and Spring 2024 in France. The number of symptomatic SARS-CoV-2 infections, hospitalizations or deaths due to COVID-19, and long COVID cases, costs and quality-adjusted life years (QALYs) were estimated using a static decision-analytic model. Predicted vaccine effectiveness (VE) were based on real-world data from the original and BA.4/5 variant-adapted vaccines, suggesting higher protection against infection and hospitalization with mRNA-1273 vaccines. VE estimates were combined with COVID-19 incidence and probability of COVID-19 severe outcomes. Uncertainty surrounding VE, vaccine coverage, infection incidence, hospitalization and mortality rates, costs and QALYs were evaluated in sensitivity analyses. In an ideal situation where 100% coverage is achieved, the mRNA-1273 variant-adapted vaccine is predicted to prevent an additional 3,882 infections, 357 hospitalizations, 81 deaths, and 326 long COVID cases when compared to BNT162b2 variant-adapted vaccines in 230,000 IC individuals. This translates to €10.1 million cost-savings from a societal perspective and 645 QALYs gained. Results were consistent across all analyses and most sensitive to variations surrounding VE and coverage. These findings highlight the importance of increasing vaccine coverage, and ability to induce higher levels of protection with mRNA-1273 formulations in this vulnerable population.
Safety and immunogenicity of full-dose quadrivalent influenza vaccine in children 6-35 months of age in China: A randomized, double-blind, clinical trial
Wang S, Wang Y, Chen D, Xu W, Duan P, Ji W, Liu W, Huang W, Wu B, Chai W, Zhao C, Yang Y, Luo J, Zhao D and Li X
A half-dose influenza vaccine (7.5 μg hemagglutinin per strain) has been used for children under 3 years of age for a long time. However, several studies indicate that a full-dose influenza vaccine (15 μg hemagglutinin per strain) may bring more benefit to this population without increasing the risk of adverse reactions. We conducted a clinical study in children aged 6-35 months in China. Participants were randomized to receive two doses of full-dose quadrivalent influenza vaccine (F-QIV), half-dose quadrivalent vaccine (H-QIV), and two half-dose trivalent vaccines (H-TIV) in a 2:2:1:1 ratio. The safety and tolerability profile of the vaccine was evaluated for 6 months postvaccination. Hemagglutination inhibition (HI) antibody titers were measured for immunogenicity assessment. The primary objective was to assess whether the results of all vaccines met the criteria. A total of 1,980 participants were enrolled in the study. Both H-QIV and F-QIV were well tolerated after vaccination. Although the geometric mean increase (GMI), seroconversion rate (SCR), and seroprotection rate (SPR) for both H-QIV and F-QIV were achieved by the criteria, superior immunogenicity in terms of geometric mean titer (GMT) ratio was observed in F-QIV to H-QIV for A/H3N2 (GMT ratio (95% CI) of 1.37 (1.11 ~ 1.68)) and B/Yamagata (1.21 (1.05 ~ 1.39)). Antibody responses to the QIV were non-inferior to the response to the TIV for the matched strains. In conclusion, F-QIV and H-QIV were both safe and immunogenic for children. F-QIV induced a stronger immune response to influenza viruses and may provide more protection and benefit by promoting the use of F-QIV in children aged 6-35 months.
Perceived barriers and facilitators to HPV vaccination: Insights from focus groups with unvaccinated mid-adults in a U.S. medically underserved area
Krishna S and Polonijo AN
Shared clinical decision-making (SCDM) about HPV vaccination has been recommended for U.S. mid-adults aged 27-45 since 2019. To explore barriers and facilitators to HPV vaccination in this population, we conducted 14 virtual focus groups with 86 unvaccinated mid-adults (34 men and 52 women) in California's medically underserved Inland Empire between September 2020 and January 2021. We systematically analyzed the focus group data using the rigorous and accelerated data reduction (RADaR) technique to identify key themes. Identified barriers included: lack of awareness, vaccine hesitancy, and perceived unaffordability (cited in 14 groups); lack of healthcare provider communication and insufficient time (13 groups); fear of moral judgment (12 groups); lack of motivation and information needs (10 groups); and lack of reliable transportation and foregone care during the COVID-19 pandemic (3 groups). Proposed facilitators included: tailored HPV vaccine information for mid-adults, cost mitigation, and improved vaccine accessibility (12 groups); healthcare provider-initiated conversations (6 groups); and vaccine reminders (4 groups). These findings highlight challenges to HPV vaccination among U.S. mid-adults eligible for SCDM and point to actionable strategies for improvement. Specifically, tailored educational interventions, decision-making tools for pharmacists, and integrating HPV vaccination into other healthcare encounters may enhance vaccination efforts in areas with limited primary care resources.
Psychometric properties of the Motors of Mpox Vaccination Acceptance Scale among men who have sex with men
Lin CY, Tsai CS, Griffiths MD, Lin CW and Yen CF
An outbreak of monkeypox (Mpox) appeared suddenly and rapidly spread worldwide during 2022. Men who have sex with men (MSM) are at a high risk of contracting Mpox compared to other cohorts. The present study examined the psychometric properties of a newly developed scale among MSM: the Motors of Mpox Vaccination Acceptance Scale (MoMVA) assessing cognitive components of the motivation to receive an Mpox vaccination. In total, 389 MSM participated in an online survey study. The factor structures of the MoMVA were first examined using exploratory factor analysis. After determining the factor structures, the MoMVA was further examined for: (i) internal consistency using Cronbach's α; (ii) concurrent validity using correlations with risk perception of contracting Mpox and intention to receive an Mpox vaccination; and (iii) known-group validity by comparing the scores of the MoMVA between MSM who vaccinated and those who did not. The results indicated that the MoMVA had a two-factor structure (positive and negative motors). The MoMVA had acceptable internal consistency (α = 0.793 to 0.914), concurrent validity (associated with intention to receive an Mpox vaccination), and known-group validity (participants who vaccinated had higher MoMVA scores than those who did not). The results of the present study indicated that the psychometric properties of the MoMVA were good and that they can be used for assessing cognitive components of the motivation to receive an Mpox vaccination among MSM.
Systematic literature review on the clinical and economic burden of human papillomavirus-related diseases in select areas in the Asia-Pacific region
Lou PJ, Phongsamart W, Sukarom I, Wu YH, Zaidi O, Du F, Simon A and Bernauer M
Compared with Europe and America, adoption of human papillomavirus (HPV) vaccination into national immunization programs across the Asia-Pacific (AP) region has remained low. Moreover, HPV burden in this region has not been reviewed comprehensively. Therefore, this systematic literature review (SLR) aimed to summarize the clinical and economic burden of HPV and HPV-related diseases in select AP areas. An SLR was conducted January 2000-February 2022 using MEDLINE/Embase. Observational studies reporting incidence, prevalence, costs, or healthcare resource utilization (HCRU) of HPV and HPV-related disease among adults (≥18 years) from select AP areas were included. A total of 254 publications were included. Reported incidence per 100,000 person-years was 15.4-252.0 for cervical cancer ( = 5 publications), 0.2-55.5 for head and neck cancer ( = 7 publications), and 0.2-13.7 for anal cancer ( = 4 publications). Prevalence rates were 9.1%-100% for cervical cancer ( = 40 publications), 0.0%-95.6% for head and neck cancer ( = 48 publications), 0.0%-100% for anal cancer ( = 4 publications), 36.0%-79.6% for penile cancer ( = 4 publications), and 44.0%-82.0% for vaginal/vulvar cancer ( = 3 publications). Few studies reported on costs or HCRU, and high data variability was observed. Despite data variability, the high burden of HPV and HPV-related diseases makes clear the need for effective HPV screening, greater education, and reductions in vaccine hesitancy, particularly among lower- and middle-income areas. Improved data collection measures should be considered in data-scarce areas to better inform policy decision-making and improve monitoring of the impact of HPV vaccination.
Medium-term immunogenicity of three doses of BNT162b2 and CoronaVac in Hong Kong neuromuscular disease patients
Yu MKL, Chan SHS, Leung D, Cheng S, Tsang LCH, Kwan TC, Zhang K, Wang X, Tu W, Peiris M, Lau YL and Rosa Duque JS
The durability of the immunogenicity elicited by three doses of mRNA-based BNT162b2 and whole-virus inactivated CoronaVac in patients with neuromuscular diseases, particularly those on immunosuppressive drugs and variants of concern, has not been well-established. Our goal was to evaluate medium-term humoral immunogenicity outcomes after 3 doses of these vaccines. Peripheral blood samples were collected from participants 14-49 days and 155-210 days after administration of the third vaccine dose to assess humoral immune responses through serological assays. The immunogenicity outcomes of each patient were compared to those of three age-matched healthy control participants, ensuring a balanced comparison. Both patients that received 3 doses of BNT162b2 and 10 (90.9%) patients that received CoronaVac seroconverted against wild-type-SARS-CoV-2 virus, showing comparable antibody responses to healthy participants. After 6 months, one patient in BNT162b2 and all four patients in CoronaVac groups maintained seropositivity. The JN-1 specific binding antibody response was lower compared to wild-type virus. The use of corticosteroids did not affect seroconversion rate against wild-type virus or JN.1 variant. BNT162b2 and CoronaVac were immunogenic for neuromuscular diseases patients, maintaining durability after 6 months even for those on corticosteroids. Our data support a rapid immunization series utilizing mRNA-based and whole-virus inactivated vaccines for future pandemic.
Correction
Immune persistence and booster response of a quadrivalent meningococcal conjugate vaccine (MenACYW-TT) 5 years after primary vaccination of adults at ≥56 years of age
Robertson CA, Jacqmein J, Selmani A, Galarza K and Oster P
Stage I of this study (NCT04142242) demonstrated the safety and immunogenicity of a booster dose of a licensed quadrivalent meningococcal tetanus toxoid-conjugate vaccine (MenACYW-TT) and immune persistence 3 and 6-7 years after priming in older adults who received either quadrivalent meningococcal polysaccharide vaccine (MPSV4) or MenACYW-TT at ≥56 years of age. Stage II, reported here, assessed the antibody persistence after MenACYW-TT versus MPSV4 priming and the safety and immunogenicity of a booster dose of MenACYW-TT in older adults 5 years after primary vaccination with either MPSV4 or MenACYW-TT. A serum bactericidal assay (hSBA) was used to measure functional antibodies against each serogroup immediately before MenACYW-TT booster vaccination and on day (D) 30 post-booster. Safety was also assessed. Antibody persistence declined 5 years post-primary vaccination, with seroprotection (hSBA titer ≥1:8) rates trending higher in MenACYW-TT- versus MPSV4-primed participants. A robust immune response for all four serogroups was observed on D30 after the MenACYW-TT booster, with higher geometric mean titers and seroprotection rates in MenACYW-TT- versus MPSV4-primed participants. Safety outcomes were similar between the two groups. A single booster dose of MenACYW-TT was well tolerated and immunogenic in older adults, with a higher immune response observed in those primed with MenACYW-TT.
AS03-adjuvanted H5N1 vaccine enhances immune response by modulating NR4A1, SDC1, ID3 genes, and reducing cortisol
Jin L, Li J and Zhu F
The AS03-adjuvanted H5N1 influenza vaccine induces significantly higher immune responses compared to the non-adjuvanted H5N1 vaccine. However, the immunological mechanisms underlying this enhancement remain unclear. We aimed to identify the key genes and pathways involved in the immune response to the AS03-adjuvanted H5N1 vaccine compared to the non-adjuvanted H5N1 vaccine. The expression profiles of GSE102012 and GSE112293 were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes between AS03-adjuvanted and non-adjuvanted H5N1 vaccine groups. Subsequently, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery online tool. The protein-protein interaction (PPI) networks were constructed by the Search Tool for the Retrieval of Interacting Genes database. Through cluster analysis of the PPI network, three hub genes, namely NR4A1, SDC1, and ID3, were identified as pivotal players in the intricate network of interactions. The ID3 was up-regulated, and the other two hub genes were down-regulated. The results of the GO analysis highlighted enrichment in seven biological processes, three cellular components, and two molecular functions among the differentially expressed genes. The KEGG pathway analysis revealed the involvement of the Cushing syndrome pathway. The AS03-adjuvanted H5N1 vaccine may enhance immune responses through suppressing the NR4A1 gene and the SDC1 gene, upregulating the ID3 gene, and reducing cortisol production compared to the non-adjuvanted H5N1 vaccine.
Immunogenicity and safety of tixagevimab-cilgavimab for COVID-19 pre-exposure prophylaxis in immunocompromised 20 to <40 kg children and adolescents: A pilot, prospective, open-labeled study
Buaboonnam J, Rungmaitree S, Piyaphanee N, Charuvanij S, Pitisuttithum O, Copeland K, Pheerapanyawaranun C, Jansarikit L, Niyomnaitham S and Chokephaibulkit K
We evaluated the immunogenicity of 300 mg Tixagevimab-Cilgavimab in immunocompromised children and adolescents who weighed 20 to >40 kg. Six to 18-year-old participants were divided into two groups by body weight and received 300 mg (20 to <40 kg) and 600 mg (≥40 kg) Tixagevimab-Cilgavimab, respectively. Anti-SARS-CoV-2 receptor-binding domain IgG concentrations and pseudovirus neutralizing antibody (NAb) titers were measured at 4, 12, and 24 weeks after administration and compared with reference data from healthy Thai children at 2 weeks after three BNT162b2 vaccinations. Of 59 participants, 49.2% were female, with a median (IQR) age of 12 (9, 15) years; 16 (27.1%) had cancer. NAb titers (95% CI) for the ancestral Wuhan strain were comparatively high for both dosing regimens (16363.2 [13765.9, 19450.5] vs 17768.3 [15539.5, 20316.9] in 20 to <40 kg and ≥40 kg participants, respectively) and significantly higher than reference titers ( < 0.001 for both). NAb titers for Omicron BA.4/5 were on par with the reference for both dosing regimens. Adverse events were mild, well tolerated, and slightly more prevalent in ≥40 kg participants who received full-dose Tixagevimab-Cilgavimab. Minimal waning in anti-RBD IgG concentrations, comparable to the reference, was observed at 12 and 24 weeks after Tixagevimab-Cilgavimab administration for both regimens. We concluded that half-dose Tixagevimab-Cilgavimab in 20 to <40 kg participants generated equivalent antibodies to standard doses in ≥40 kg participants and significantly higher antibodies than three-dose BNT162b2 vaccination. Further study of monoclonal long-acting antibodies in larger cohorts and <6-year-old children are warranted.
Causal impacts of 731 immunocyte phenotypes on colorectal cancer-evidence from a bidirectional two-sample Mendelian randomization
Gu X, Zhao S, Xia M, Du S, Song L, Xia T and Zhang B
Colorectal cancer is one of the most common and lethal malignancies, and various factors have been confirmed to contribute to its occurrence. However, the causal role of immune cell-specific changes in the development of colorectal cancer has not been investigated. The bidirectional two-sample Mendelian randomization analysis was performed to explore the association between 731 types of immune cell phenotypes-specific changes and colorectal cancer. The inverse variance weighting results indicated that a total of 31 and 28 immune cell phenotypes significantly associated with colorectal cancer in two different datasets, respectively. The primary results of inverse variance weighting Mendelian randomization suggested that the immune cell phenotypes BAFF-R on IgD+ CD38dim (OR = 1.033, 95%CI: 1.005-1.062) and SSC-A on monocyte (OR = 1.055, 95%CI: 1.016-1.096) served as risk factor for colorectal cancer. In addition, the meta-analysis further supports the causal link of BAFF-R on IgD+ CD38dim (pooled OR = 1.035, 95%CI: 1.013-1.059) and SSC-A on monocyte (pooled OR = 1.060, 95%CI: 1.026-1.095) with colorectal cancer. Finally, the inverse variance weighting Mendelian randomization result suggested that genetic determinants of colorectal cancer may decrease the level of HLA DR++ monocyte absolute count (OR = 0.686, 95%CI: 0.508-0.925). Our results indicated that the potential causal association of BAFF-R on IgD+ CD38dim and SSC-A on monocyte with colorectal cancer. The identified immune cells may be appealing drug targets for colorectal cancer, but lack confirmation from real clinical evidence. Further studies are needed to investigate the roles of these immune cells in colorectal cancer.
Safety profiles of intravesical Bacillus Calmette-Guerin in bladder cancer
Peng Y, Song Y, Qin C, Du Y and Xu T
Bladder cancer (BCa) exhibits significant sex disparities, and intravesical Bacillus Calmette-Guerin (BCG) is a widely used treatment for non-muscle invasive bladder cancer (NMIBC). A comprehensive evaluation of intravesical BCG, including the safety profile and adverse events (AEs), is essential. In particular, exploring the sex differences is crucial. We conducted a pharmacovigilance data analysis using real-world big data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. In our study, we analyzed 3,374 cases of intravesical BCG for signal mining. We detected 353 signals at the Preferred Term (PT) level and 10 signals at the System Organ Class (SOC) level when compared to the full FAERS database. When comparing between intravesical BCG and other administration routes, we identified 14 signals at the PT level and 8 signals at the SOC level. Intravesical BCG exhibited lower immune-related AEs (irAEs) risk than anti-PD-1/PD-L1 treatment, but antibiotics increased the risk. Notably, AEs associated with intravesical BCG exhibited significant sex differences. Female patients showed a higher susceptibility to developing allergic diseases such as Reiter's syndrome and Arthralgia, while male patients were more prone to infectious diseases. Additionally, we highlighted that male patients had higher fatality rates, whereas female patients experienced higher rates of recurrence and irAEs. We have compiled an overview of AEs associated with intravesical BCG. These findings enhance understanding of safety profiles and risks, enabling informed decisions prioritizing patients.
Seasonal influenza vaccines: Variability of immune responses to B lineage viruses
Miller MS, Montomoli E, Leshem E, Schotsaert M, Weinke T, Vicic N and Rudin D
Although influenza A viruses predominate globally, influenza B viruses are responsible for a significant and often underappreciated burden. Despite this, immunity to influenza B viruses remains understudied, and there is a perception that vaccine-mediated immune responses to influenza B strains are less robust than influenza A strains. This targeted literature review examines this concept using data from pivotal phase 3 immunogenicity studies on currently licensed seasonal influenza vaccines and explores several explanations for this phenomenon, including immune exposure history, assay limitations, virus-related properties inherent to B lineages, and strain mismatch. Overall, studies demonstrated vaccines induce variable and sometimes less robust immune responses to influenza B strains; however, further studies are needed to fully confirm and understand these observations. In identifying the potential causes of variable performance of current vaccines against influenza, this review aims to guide vaccine development to enhance overall vaccine performance and reduce disease burden worldwide.
Epidemiological characteristics of breakthrough mumps infection cases from 2019 to 2023 in Chongqing, China
Liu Y, Cai X, Yang D, Xiang Y, Wang Q, Yao N, Zhang Y and Xu J
The high coverage of mumps-containing vaccine (MuCV) has effectively controlled the mumps incidence, while the prevention and control of breakthrough cases has become a prominent problem. To analyze the epidemiology of mumps breakthrough cases in Chongqing from 2019 to 2023, and provide scientific evidence for the prevention and control of mumps. The data of clinical and laboratory-confirmed mumps cases in Chongqing from 2019 to 2023 were exported from the China Information System for Disease Control and Prevention. The immunization history was screened and matched from the Chongqing Immunization Program Information System. Least-Significant Difference (LSD) and T-test were used for data analysis. There were 12,566 breakthrough cases in Chongqing, accounting for 61.09% of the total mumps cases reported. The most breakthrough infection occurred in the 3-9 years age group. In 2019 and 2020, the mean age of breakthrough cases with two doses was older than that with one dose ( < .05). In 2022 and 2023, the age was younger than that with one dose ( < .05). The breakthrough intervals for one dose and two doses were (4.87 ± 2.57) and (2.01 ± 1.79) years, respectively. The proportion of breakthrough mumps cases continues to increase in highly vaccinated populations in Chongqing. It is necessary to carry out research on a supplementary dose of MuCV vaccination strategy, and enhance the monitoring of mumps outbreaks in key populations such as children in kindergartens and primary schools.
Seroepidemiology of pertussis immunity in five provinces of China: A population-based, cross-sectional study
Zhang Z, Wang Q, Zhu Q, Bai S, Liu Y, Ren J, Xu X, Qu J, Pan J, Lu L, Suo L, Sun X, Zhang Y and Wu J
This study aimed to evaluate the seroprevalence of and persistence of antibodies following vaccination. We recruited 6060 healthy subjects from five provinces of China during 2017-2018. Serum IgG antibodies against pertussis toxin (anti-PT IgG) and filamentous hemagglutinin (anti-FHA IgG), and serum IgA antibodies against pertussis toxin (anti-PT IgA) were measured by ELISA. Geometric mean concentration (GMC), seropositivity rate, and recent infection rate were calculated. Among 0-6 years-olds, the anti-PT IgG, anti-PT IgA, and anti-FHA IgG GMCs were 6.4 IU/ml (95% CI 6.1-6.8), 2.8 IU/ml (95% CI 2.7-2.8), and 13.3 IU/ml (95% CI 12.4-14.2), respectively. The anti-PT IgG GMC increased in accordance with the primary vaccination series (4-6 months) and the toddler booster (18-24 months), but declined thereafter through to age 5 years [4.7 IU/ml (95% CI 4.2-5.4)]. The seropositivity rate of pertussis in >6 year-olds was 9.0% (95% CI 8.1-9.9) and the recent infection rate was 3.3% (95% CI, 2.7-3.8). Recent infection rate began to increase from 6 years of age, with peaks at 9, 20, 40, and ≥60 years of age. The anti-PT IgG GMCs of children aged 0-6 years who were vaccinated with DTaP, DTaP-IPV//PRP~T, and DTaP-Hib were 5.9 IU/ml (95% CI 5.6-6.3), 20.7 IU/ml (95% CI 15.6-27.8), and 11.7 IU/ml (95% CI 7.5-18.1) ( < .001), respectively ( < .001). Pertussis vaccination improves anti-PT IgG levels, however these wane soon after vaccination. Sero-estimated recent infection rates appear to increase from school age into adolescence and adulthood. Pertussis vaccine boosters should be considered in these age groups.
A randomized clinical trial of the impact of melatonin on influenza vaccine: Outcomes from the melatonin and vaccine response immunity and chronobiology study (MAVRICS)
Lee RU, Watson NL, Glickman GL, White L, Isidean SD, Porter CK, Hollis-Perry M, Walther SR, Maiolatesi S, Sedegah M, Ganeshan H, Huang J, Boulifard DA, Ewing D, Sundaram AK, Harrison EM, DeTizio K, Belmonte M, Belmonte A, Inoue S, Easterling A, Cooper ES and Danko J
Vaccine immunogenicity is affected by a variety of factors. Melatonin has been reported to affect immune responses to vaccines and infection. This was a randomized open-label trial - in which adults scheduled to receive the influenza vaccine were randomized to 5 mg melatonin or control to evaluate the effect of post-vaccination melatonin on humoral (hemagglutination-inhibition assays, HAI) and cellular (FluoroSpot) vaccine-specific cytokine responses 14-21 days post-vaccination. A total of 108 participants (melatonin treatment group: 53; control group: 55) completed the study. The groups were similar in baseline characteristics, including sleep as measured by the Pittsburgh Sleep Quality Index. Seroconversion rates or geometric mean fold rises (GMFR) in HAI titers did not vary by treatment group. There were also no statistically significant differences between pre- and post-vaccination levels of interferon gamma (IFN-γ) or granzyme B (GzB) by treatment; however, there was a significantly higher fold rise in the double secretor (IFN-γ + GzB) peripheral blood mononuclear cells for influenza vaccine in subjects taking daily melatonin (GMFR 1.7; 95% CI 1.3, 2.3) compared to those who did not (GMFR 0.9; 95% CI 0.7, 1.1) ( < .001). Daily melatonin for 14 days post-influenza vaccination significantly increased the cellular co-expression of IFN-γ + GzB; however, there were no other differences in the cellular or humoral responses. Future studies of the potential utility of melatonin for enhancing vaccine response with larger sample sizes may help elucidate candidate mechanisms for these limited effects, including any interactions with the circadian system.
Knowledge mapping and research trends of IL-22 from 2014 to 2023: A bibliometric analysis
Liu SZ, Xie JH, Yan BJ and Wang J
Although IL-22 has been extensively studied, a comprehensive and systematic bibliometric analysis has not yet been conducted on it. This article reviews the research progress of IL-22 using bibliometric methods. On May 20, 2024, publications related to IL-22 were identified and selected from the Web of Science Core Collection (WoSCC) database. CiteSpace and VOSviewer are beneficial for IL-22 bibliometric and knowledge graph analysis. From January 1, 2014 to December 31, 2023, 25134 authors from 4206 institutions in 106 countries published 3943 articles on IL-22 research in 940 academic journals. During this period, the number of articles steadily increased. The United States and China are the main contributors to this research field, with the most active institutions being the Medical Research Institute (INSERM) led by De la Sante et al. and the University of California system. The most prolific journal is Frontiers of Immunology, and it is also the journal with the most citations. Guttman Yassky, E. has published the most articles, and Guttman Yassky, E. is also the most frequently cited. The main areas of these publications are immunology and cell biology. After analysis, the high-frequency keywords of IL-22 research involve molecular biology (IL-17) and immune response (T cells) Th17 cells and diseases (autoimmune diseases, cancer). Among them, the involvement of interleukin-22 in microbial populations and cancer cell spread has strong research potential and is currently a hot research topic. Since 2014, IL-22 has received significant attention in scientific research as a key immune regulatory factor. China is at the forefront of research in this field, followed closely by the United States. At present, breakthrough progress is being made in the research of immunotherapy, and in-depth study of IL-22 and its signal transduction mechanisms is crucial for understanding its biological functions. Meanwhile, exploring new possibilities for IL-22 as a therapeutic target will help develop more effective treatment strategies. This study can provide scholars with research directions related to IL-22.
Establishment of potent TCR-T cells specific for cisplatin-resistance related tumor-associated antigen, CLSPN using codon-optimization
Hori K, Yamada S, Murata K, Miyata H, Mizue Y, Murai A, Minowa T, Sasaki K, Shijubou N, Kubo T, Morita R, Tokita S, Kanaseki T, Tsukahara T, Abe T, Shinohara N, Hirohashi Y and Torigoe T
Adoptive T cell therapy, using T cell receptor-engineered T (TCR-T) cells and chimeric antigen receptor T (CAR-T) cells, is a potent immunotherapy option. Bladder cancer is a prevalent urological malignancy, particularly in cases of muscle invasion and metastasis, for which systemic therapy is crucial. Immunotherapy utilizing immune checkpoint blockade has been approved for bladder cancer treatment. The antitumor effect of an immune checkpoint blockade based on cytotoxic T cells (CTLs) and the patient's immune status is essential. The chemotherapeutic drug cisplatin (CDDP) is a key drug in bladder cancer treatment. However, it has been shown to suppress T cells, making combination therapy with CDDP and immunotherapy difficult. To address this, we developed TCR-T cells specific for bladder cancer cells. In previous studies, we found that the tumor-associated antigen CLSPN is overexpressed in CDDP-resistant bladder cancer cells and that the antigenic peptide HLA-A*02:01/CLSPN, encoded by CLSPN, could be targeted by a CTL clone. The TCR was cloned from the HLA-A*02:01/CLSPN specific CTL clone yc3. We also designed a codon-optimized TCR sequence using GeneArt® GeneOptimizer® (Opt TCR) and compared the TCR-T cells using the original TCR sequence (Ori TCR-T cells) and the codon-optimized TCR sequence (Opt TCR-T cells). Opt TCR-T cells exhibited higher TCR transduction efficiency, higher TCR expression levels, higher avidity, and greater cytotoxicity than did Ori TCR-T cells. These results suggest that HLA-A*02:01/CLSPN specific Opt TCR-T cells are promising candidates for CDDP combination therapy.
A visualization analysis of immune-related adverse reactions in pulmonary carcinoma
Gong Y, Kang J, Wang M, Firdaus Mohd Hayati M, Wah Goh LP and Bin Syed Abdul Rahim SS
Immunotherapy has emerged as a crucial advancement in pulmonary carcinoma treatment. Nevertheless, its unique side effects not only reduce patients' quality of life but also affect treatment efficacy, with severe cases potentially endangering the patient's life. This study uses bibliometric analysis to perform a comprehensive bibliometric analysis literature on IRAEs in lung cancer from 1991 to 2023, retrieved from the Web of Science database. The dataset was analyzed using VOSviewer and CiteSpace to identify trends, key contributors, and emerging research areas. A total of 124 publications were analyzed, revealing a notable increase in research activity post-2015, with China and the USA contributing over 50% of the studies. This research highlights the importance of understanding IRAEs and suggests future investigations into the pulmonary microbiota and tumor microenvironment.