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Exploring determinants of vaccine hesitancy among healthcare professionals: a systematic literature review.

INTRODUCTION: This systematic review aims to assess determinants of vaccine hesitancy (VH) among healthcare professionals, to identify knowledge gaps and inform targeted training programs. RESEARCH DESIGN AND METHODS: A systematic search of PubMed and Scopus was conducted in February 2024. PRISMA criteria were applied, and methodological quality was assessed using a cross-sectional study evaluation tool. Studies addressing HCWs' VH determinants, including knowledge, attitudes, communication, and organizational factors, were included. RESULTS: Out of 1394 records, 221 articles were included. Reported prevalence of VH among HCWs varied across studies, reflecting differences in professional roles, settings, and vaccines studied. Key determinants included gaps in knowledge, personal beliefs, organizational barriers, and communication skills. The review highlights the importance of evidence-based information, continuing education, and effective communication in addressing VH among HCWs. CONCLUSIONS: Educational and organizational interventions are essential to improve HCWs' knowledge, attitudes, and practices regarding vaccination. Strengthening vaccine education, fostering effective communication, and addressing organizational challenges can reduce hesitancy and support HCWs in promoting vaccination among patients. Future initiatives should consider the diversity of educational settings, professional roles, and training requirements across healthcare systems.

Humans

Safety of a quadrivalent meningococcal conjugate vaccine (MenACYW-TT) administered concomitantly with routine pediatric vaccines in healthy infants and toddlers in USA and Puerto Rico: Results from a Phase III, randomized, active-controlled study.

MenACYW-TT, a quadrivalent meningococcal tetanus toxoid-conjugate vaccine, is approved for prevention of invasive meningococcal disease in infants ≥ 6 weeks of age in the USA. This Phase III study (NCT03673462; September 17, 2018 - March 16, 2023) evaluated the safety of MenACYW-TT compared with a licensed quadrivalent meningococcal oligosaccharide diphtheria CRM197-conjugate vaccine (MenACWY-CRM) when administered concomitantly with routine pediatric vaccines in healthy infants and toddlers in a four-dose series (3+1 schedule). Participants were randomized 3:1 to receive MenACYW-TT (Group 1; n = 2080) or MenACWY-CRM (Group 2; n = 697) at 2, 4, 6, and 12 months of age, with concomitant administration of routine pediatric vaccines (DTaP5-IPV/Hib, PCV13, rotavirus, hepatitis B, MMR, and varicella vaccines). Safety assessments included immediate unsolicited adverse events within 30 minutes post-vaccination, solicited injection site and systemic reactions within 7d, unsolicited AEs within 30d, serious adverse events (SAEs) including adverse events of special interest (AESIs), and medically attended adverse events (MAAEs) throughout the study. MenACYW-TT and MenACWY-CRM were overall well tolerated, and safety profiles were comparable. Solicited injection site reactions occurred in 84.9% and 84.6% of participants in Groups 1 and 2, respectively; solicited systemic reactions in 87.1% and 88.2%, respectively. During the entire study, 5.2% in Group 1 and 3.0% in Group 2 experienced at least one SAE; 0.9% and 0.1%, respectively, reported at least one AESI. Three deaths occurred in Group 1. All SAEs, AESIs, and deaths were unrelated to study vaccines. This study supports the safety profile of MenACYW-TT in infants and toddlers aged ≥ 6 weeks.Study registration: Clinicaltrials.gov: NCT03673462; EudraCT: 2019-004459-35.

Child, Preschool

Dengue and chikungunya vaccines past, present and future: implications for travelers.

PURPOSE OF REVIEW: Novel vaccines for dengue and chikungunya viruses offer new prevention options against two globally important arboviral diseases. This review summarizes recent developments in vaccine licensure, implementation, real-world experience and research priorities, with emphasis on implications for both endemic populations and travelers. RECENT FINDINGS: Of the three live-attenuated dengue vaccines licensed to date, TAK-003 is authorized in >40 countries and Butantan-DV in Brazil, while manufacturing of CYD-TDV is discontinued. Long-term and postmarketing data continue to refine understanding of serotype-specific protection, waning immunity, and rare adverse events.For chikungunya, two single-dose vaccines are licensed-a live-attenuated vaccine (VLA1553) and virus-like particle vaccine (PXVX0317). Uptake is guided by emerging safety and effectiveness data, with each platform offering potential advantages in different settings.Further data on long-term protection, safety, effectiveness, use in vulnerable populations and integration into outbreak management and immunization systems is anticipated. SUMMARY: Dengue and chikungunya vaccines are increasingly being used in immunization programs and pretravel consultations. Further real-world data are needed-particularly for seronegative dengue vaccine recipients and older, immunocompromised or medically at-risk adults. Research priorities include developing single-dose, nonlive dengue vaccines suitable for high-risk groups, understanding long-term chikungunya vaccine performance, and exploring broader flaviviral or pan-arboviral platforms.

Humans

Comparison of immunogenicity, safety, and efficacy of EVA71 vaccine in children: a systematic review and meta-analysis.

INTRODUCTION: Enterovirus 71 (EV-A71) is a principal cause of hand, foot, and mouth disease (HFMD), potentially leading to severe neurological complications in children. Inactivated EV-A71 vaccines have been introduced. This study compares the immunogenicity, safety, and efficacy of EV-A71 vaccines versus placebo in pediatric populations. RESEARCH DESIGN AND METHODS: Following a PROSPERO-registered protocol, RCTs involving EV-A71 in children were identified via PubMed, Scopus, Cochrane, and ClinicalTrials.gov. Two independent reviewers performed screening, extraction, and RoB assessments (RoB 2.0). RESULTS: Five phase III RCTs involving 36,659 children were included. EV-A71 vaccination significantly increased seropositivity across follow-up periods, including early (RR 5.8), medium-term (RR 3.09), and long-term (RR 2.95) response. Seroconversion was significantly higher in the vaccinated group (pooled RR 13.04, 95% CI 2.80-60.61; p&#x2009;<&#x2009;0.001). Geometric mean titers, analyzed using the ratio of means approach, were significantly higher in the vaccinated group during early and medium-term follow-up. Vaccine efficacy against EV-A71-associated HFMD exceeded 98% (pooled RR 0.02, 95% CI 0.01-0.09; p = 0.0028; I2&#x2009;=&#x2009;50%). Solicited local and systemic adverse events were mild and comparable between groups. CONCLUSION: Inactivated EV-A71 vaccines robust immunogenicity, high clinical efficacy, and an acceptable safety profile in children. Future studies should explore long-term protection, booster schedules, and multivalent formulations against non-EV-A71 serotypes.

Humans

Molecular characterization of 16 MAPK genes in silver carp (Hypophthalmichthys molitrix) and the differences of their mRNA expression between Qiandao Lake and Taihu Lake.

Mitogen-activated protein kinase (MAPK), a serine-threonine protein kinase, is involved in a variety of stress-induced responses and also plays an important regulatory role in cell metabolism. In the study the open reading frames (ORFs) of 16 MAPK genes in silver carp (Hypophthalmichthys molitrix) were obtained and verified, with the evaluations of their taxonomy, structures, conserved motifs, and evolutionary linkages. And the expression patterns of these genes in the silver carp from Qiandao Lake and Taihu Lake were explored for better understanding the response of MAPK genes to different water environment. MAPK genes of silver carp were divided into three subfamilies, including extracellular signal-regulated kinase (ERK) subfamily, p38 subfamily and C-Jun N-terminal kinase (JNK) subfamily. All these genes possessed similar structures and conserved motifs of MAPK family. Realtime qPCR revealed that the expression patterns of 10 MAPK genes (ScMAPK1, ScMAPK3, ScMAPK4, ScMAPK7, ScMAPK15, ScMAPK8a, ScMAPK8b, ScMAPK9, ScMAPK10 and ScMAPK11) in head kidney, spleen and gill of silver carp in Taihu Lake and Qiandao Lake were different. These findings provide a basis for further research on the function of MAPK in silver carp.

Animals

A multi-center, open-labelled, randomized controlled extended phase III non-inferiority clinical trial to evaluate the immunogenicity and tolerability of poliomyelitis vaccine (Vero cells), inactivated, Sabin strains administered with or without routine infant vaccines.

BACKGROUND: Oral poliovirus vaccine (OPV) has been reported to cause vaccine-derived poliovirus and vaccine-associated paralytic poliomyelitis, and the limited global supply of conventional IPV has led many countries to rely on fractional-dose IPV regimens alongside OPV. The current study aims to assess the sIPV safety and immunogenicity when given concurrently with or in a staggered manner with routine immunization. METHODS: A multi-country, multi-center, open-label, randomized controlled, extended phase III non-inferiority clinical trial was conducted with 1442 healthy infants aged 6-8&#xa0;weeks from Bangladesh and Pakistan enrolled and randomized into four groups, i.e., co-administration group 1 (group C1), co-administration group 2 (group C2), staggered administration group 1 (group S1) and staggered administration group 2 (group S2). Antibody levels were determined using the collected sera for immunogenicity evaluation. The difference in seroconversion rates between the coadministration group and the staggered administration group is compared using the Cochran-Mantel-Haenszel &#x3c7;2 (CMH-&#x3c7;2) test, stratified by study site. Non-inferiority is concluded if the lower bound of the 95% confidence interval (CI) for the rate difference (coadministration group minus staggered administration group) is greater than -10%. The trial was registered prior to patient enrollment at clinicaltrials.gov (NCT05850364), and the protocol and statistical analysis plan are available at https://clinicaltrials.gov/study/NCT05850364. The trial is closed to new participants. FINDINGS: The post-vaccination seroconversion rates for PV I were 90.3% (306/339) in group C1 and 87.0% (261/300) in group S1, for PV II, 91.7% (311/339) in group C1 and 91.3% (274/300) in group S1 and for PV III, 86.4% (293/339) in group C1 and 92.3% (277/300) in group S1. Among adverse reactions (ARs) reported within 7&#xa0;days of vaccination, the incidence was similarly high in both the co-administration and staggered vaccination groups (92.8% vs. 95.5%). INTERPRETATION: Our results demonstrated favorable safety and immunogenicity of co-administration of sIPV with other routine infant vaccines according to a 3-dose primary immunization schedule.

Humans

Immunogenicity of Two Versus Three Doses of Hepatitis B Vaccine When Administered to Children Aged 2-18 Months: A Randomized Clinical Trial.

BACKGROUND: A 2-dose hepatitis B vaccination schedule is highly immunogenic in children aged &#x2265;1 year, but data for infants are scarce. Our goal was to compare the immunogenicity of 2- and 3-dose hepatitis B vaccination schedules in this population. METHODS: Children in the experimental group were recruited at 2 months of age and randomized to receive a homologous (Infanrix-hexa/Infanrix-hexa) or heterologous (Infanrix-hexa/Twinrix) 2-dose schedule at 2 and 12 months. Children in the control group were recruited at 18 months and had received a homologous 3-dose schedule (Infanrix-hexa/Infanrix-hexa/Infanrix-hexa) at 2, 4, and 18 months. All groups received a challenge dose (Twinrix) 3 years later. RESULTS: One month after the primary series, seroprotection rates (anti-HBs &#x2265;10 mIU/mL) were high and similar among the 3 groups (heterologous 2-dose, 91.7%; homologous 2-dose, 90.9%; 3-dose, 94.2%). Geometric mean titers (GMTs) were lower in the 2-dose groups than in the 3-dose group. Post-challenge dose, the majority exhibited an anamnestic response, similar across all 3 groups (heterologous 2-dose, 97.2%; homologous 2-dose, 95.5%; 3-dose, 92.7%). GMTs were numerically higher in the heterologous 2-dose group (9380.5 mIU/mL) than in the 3-dose group (6900.6 mIU/mL) (P = .4). The proportion exhibiting local reactions was significantly lower after the heterologous 2-dose schedule than after the homologous 2-dose schedule. CONCLUSIONS: The anamnestic response 3 years after 2-dose (2 and 12 months) and 3-dose (2, 4, and 18 months) hepatitis B vaccination schedules was similar. The heterologous 2-dose schedule was more immunogenic and less reactogenic than the homologous 2-dose schedule.

Humans

Maternal vaccination with RSVpreF and risk of hypertensive disorders of pregnancy: a systematic review and meta-analysis.

BACKGROUND: A bivalent respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVpreF) was approved in the United States in August 2023 for use during pregnancy to prevent infant RSV-associated lower respiratory tract disease. The pivotal phase 3 trial identified a numerical imbalance in hypertensive disorders of pregnancy (HDP) that did not reach statistical significance; postmarketing observational studies have since reported inconsistent findings. We conducted a systematic review and meta-analysis to assess this association. METHODS: We searched MEDLINE, Embase, CENTRAL, Scopus, ClinicalTrials.gov, and WHO ICTRP from inception to Jan 26, 2026, for randomized controlled trials (RCTs) and observational studies comparing HDP outcomes in RSVpreF-vaccinated versus unvaccinated or placebo-receiving pregnant individuals. Unadjusted risk ratios (RRs) were pooled using a random-effects model; adjusted estimates from observational studies were pooled separately by inverse variance methods. This study is registered with PROSPERO (CRD420251026835). RESULTS: Nine studies were included (3 RCTs, 6 retrospective cohort studies; n&#xa0;=&#xa0;148,267). RSVpreF vaccination was associated with a small but statistically significant increase in overall HDP risk (RR 1&#xb7;08, 95% CI 1&#xb7;02-1&#xb7;13; p&#xa0;=&#xa0;0&#xb7;004; I2&#xa0;=&#xa0;44%), driven by the observational studies group (1&#xb7;08, 1&#xb7;02-1&#xb7;14; I2&#xa0;=&#xa0;61%); RCTs showed a directionally consistent but non-significant RR (1&#xb7;12, 0&#xb7;87-1&#xb7;43; I2&#xa0;=&#xa0;0%). The association was attributable to gestational hypertension, with no significant association for preeclampsia/eclampsia. CONCLUSION: Maternal RSVpreF vaccination was associated with a small increase in HDP attributable to gestational hypertension and driven primarily by observational studies, in which residual confounding remains possible. The benefits of infant RSV prevention remain substantial, and these findings support continued postmarketing surveillance and informed shared decision-making.

Humans

Safety and Immunogenicity of Varicella Vaccination in Children and Adolescents Living With HIV: A Systematic Review.

INTRODUCTION: Preventing varicella-zoster virus infection is important in the management of human immunodeficiency virus (HIV)-positive persons. Varicella remains endemic worldwide, and HIV-positive persons can experience greater morbidity than the general population. We summarized the global literature on the safety and immunogenicity of the varicella vaccine in HIV-positive children. METHODS: Systematic review of original reports on varicella vaccination of HIV-positive children, published through December 31, 2024, including assessment of safety, immunologic responses and effectiveness after vaccination. RESULTS: Eighteen articles were analyzed. Local reactions were the most common adverse events, albeit infrequent (<21% and <10% of vaccinees after dose 1 and 2, respectively). Systemic reactions were also infrequent, consisting mostly of low-grade fever. A vaccine-related rash, reported in <5% of vaccinees, had fewer lesions and a shorter duration than typical varicella. Serious adverse events were reported only when the vaccine was inadvertently administered to children with severe HIV immunosuppression. Varicella vaccination had no clinically significant impact on plasma HIV RNA or CD4+ T-cell count after either dose. An antibody response was reported in 60%-79% of HIV-positive vaccinees after dose 2 and often declined more rapidly than in uninfected children. Cell-mediated immunity was detected in 67%-83% after dose 2. No significant differences in adverse events or short-term immune response after vaccination correlated with past or current CD4+ T-cell status. CONCLUSIONS: The varicella vaccine had a favorable safety profile and induced specific immune responses in most nonseverely immunocompromised HIV-positive children. The vaccine remains contraindicated for persons with severe HIV infection. Robust data on the durability of immune response and long-term effectiveness are needed.

Humans

Immunogenicity and safety of prophylactic HPV vaccines in people living with HIV: A systematic review and meta-analysis.

Human papillomavirus (HPV) is a major global public health concern, causing genital warts and cancers of the cervix, anus, oropharynx, vulva, and penis. People living with HIV (PLWH) face a disproportionately elevated burden of HPV infection and HPV-related malignancies due to chronic immunosuppression. We conducted a systematic review and meta-analysis searching six databases from January 2006 to June 2026 without language restrictions. Twenty-five studies were included in the systematic review; 12 independent studies (N&#x2009;=&#x2009;1,493 for HPV16) were included in the quantitative meta-analysis. Using a DerSimonian-Laird random-effects model with logit transformation, pooled seroconversion rates were: HPV16 97.8% (95% CI: 94.9-99.1%; I2&#x2009;=&#x2009;89.6%; 15 datasets), HPV18 94.2% (95% CI: 86.1-97.7%; I2&#x2009;=&#x2009;95.8%; 13 datasets), HPV6 97.0% (95% CI: 93.7-98.6%; I2&#x2009;=&#x2009;66.1%; 10 studies), and HPV11 97.1% (95% CI: 90.5-99.1%; I2&#x2009;=&#x2009;95.5%; 10 studies). CD4 count was the most consistently reported modifier of immunogenic response: HPV16 seroconversion was 98.5% in PLWH with CD4&#x2009;>&#x2009;350 cells/&#x3bc;L vs. 71.1% in those with CD4&#x2009;&#x2264;&#x2009;200 cells/&#x3bc;L (ACTG A5240). All three vaccine generations demonstrated high immunogenicity. Two doses of the nonavalent vaccine were non-inferior to three doses in virologically suppressed women (Papillon RCT). No vaccine-related serious adverse events were reported. GRADE certainty of evidence was moderate for HPV16, HPV6, and HPV11, and low for HPV18. Prophylactic HPV vaccination achieves high seroconversion rates across all vaccine generations in PLWH. CD4 count significantly modifies vaccine response, underscoring the importance of vaccination before severe immunosuppression develops. These findings support current international recommendations advocating HPV vaccination for all PLWH.

Humans

Immunogenicity and safety of inactivated TZ84- vs. HM175-based hepatitis A vaccines in pediatric populations: A systematic review and meta-analysis.

Individual studies indicate stronger and persistent long-term immunogenicity with TZ84-based than HM175-based hepatitis A vaccines. This systematic review and meta-analysis compared immunogenicity and safety of inactivated TZ84- and HM175-based hepatitis A vaccines in children and adolescents. Studies involving adults, immunocompromised populations, non-comparative designs, non-English publications, and studies with non-extractable outcomes were excluded. MEDLINE/PubMed, Google Scholar, other electronic databases, and grey literature were searched (September-October 2025). Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, and meta-analyses were performed where appropriate. Seven publications arising from four randomized cohorts (total participants: 3,282) reporting seroconversion rates (SCRs), geometric mean concentrations (GMCs), long-term seroprotection, and adverse events (AEs) were identified. Pooled analyses demonstrated higher SCRs and GMCs with TZ84 than HM175-based vaccines following both one and two doses. SCRs at 1&#x2009;month [odds ratio (OR): 3.05; 95% confidence interval (CI): 1.88-4.96] and GMCs at 7&#x2009;months [standardized mean difference (SMD): 0.88; 95% CI: 0.18-1.58; p&#x2009;=&#x2009;.01] both favored TZ84-based vaccines. Long-term follow-up (up to 186&#x2009;months/15.5 y) showed higher reported anti-HAV antibody concentrations for TZ84-based vaccines. The AEs were comparable between vaccine types (RR: 0.95; 95% CI: 0.76-1.20; p&#x2009;=&#x2009;.69). Evidence was limited by the small number of unique randomized cohorts, geographic concentration in China, heterogeneity across studies, and reliance on surrogate immunogenicity outcomes. Overall, available evidence suggests that TZ84-based hepatitis A vaccines (HAPIBEV&#x2122;/HEALIVE&#xae;) are associated with higher reported antibody responses and greater reported antibody persistence than the HM175-based vaccine (HAVRIX&#xae;) in children and adolescents, with comparable safety profiles.Registration: PROSPERO CRD420251154480.

Humans

Pre-clinical immunogenicity and safety evaluation of H2 strain Hepatitis A Inactivated Vaccine in rhesus macaques.

BACKGROUND: Hepatitis A is a viral infection of the liver that can cause mild to severe illness. Currently, two types of HAV vaccines are used worldwide, inactivated hepatitis A vaccines, which are used in most countries, and live attenuated vaccines (H2 and L-A-1 strain), which are mainly used in China. The major disadvantage of live attenuated virus to cause secondary infections among contacts and mutation shifts of the live vaccine strain. The H2 strain was selected for the development of an inactivated hepatitis A vaccine to further reduce biosafety risks. Rhesus macaques high genomic homology with humans and the incubation period after hepatitis A vaccination and human natural infections are similar. We use rhesus macaques to assess immunogenicity and safety of the H2 strain Hepatitis A Inactivated Vaccine. METHODS: The vaccine was assessed in rhesus macaques, divided into four groups (n&#x202f;=&#x202f;10 per group): the control group (adjuvant buffer; aluminum content 0.35&#x202f;mg/mL; 2&#x202f;mL per dose), the low-dose group (320EU, 0.5&#x202f;mL of 640EU/mL with aluminum content 0.35&#x202f;mg/mL), the medium-dose group (640EU, 1&#x202f;mL of 640EU/mL with aluminum content 0.35&#x202f;mg/mL), and the high-dose group (1280EU, 2&#x202f;mL of 640EU/mL with aluminum content 0.35&#x202f;mg/mL). Animals were injected intramuscularly at multiple sites in the hind limbs and received four inoculations at 4-week intervals. Test items including Clinical indicators, immunogenicity indicators and Histopathological examination. RESULTS: No abnormalities were observed in any group in terms of general clinical condition throughout the study period except for slight decreases in body temperature after immunization. Hematological parameters, serum biochemistry indices, and histopathological findings showed fluctuated to different degrees of fluctuation after immunization across all groups. Immunogenicity assessments showed that the inactivated hepatitis A vaccine (H2) induced both humoral and cellular immune responses effectively, and the levels of antibodies increased with certain dose- and time-response trends. CONCLUSION: The inactivated hepatitis A vaccine (H2 strain, human diploid cell) was safe and immunogenic in non-human primates. The results provide strong preclinical support for the further clinical development of this vaccine candidate.

Animals

Recombinant vs Standard Influenza Vaccine in Adults With Severe Obesity: A Randomized Clinical Trial.

BACKGROUND: Individuals with severe obesity are at increased risk of severe influenza and may have impaired immune responses to vaccination. Recombinant influenza vaccine (RIV) may provide enhanced protection compared with egg-based standard-dose influenza vaccine (SD), but data in this high-risk population are limited. METHODS: The AP-HP FLUO trial (NCT05409612) was an open-label, randomized clinical trial conducted in 15 centers in France (November 2022-March 2023) with 6 months of follow-up. Adults with BMI &#x2265;35 kg/m2 were randomized 1:1 to receive RIV or SD, using minimization by center, age (<50 vs &#x2265;50 years), and BMI (<40 vs &#x2265;40 kg/m2). The primary outcome was the ratio (RIV/SD) of geometric mean hemagglutinin-inhibition (HAI) titers (GMTs) for 4 influenza strains 28 days after vaccination. Safety and reactogenicity were also assessed. RESULTS: A total of 206 participants were included (104 RIV, 102 SD). Median age was 50 years, 60.2% were women, and median BMI was 41.0 kg/m2. At Day 28, GMT ratios favored RIV for A/H1N1 (1.6; 95% CI, 1.1-2.3), A/H3N2 (2.0; 95% CI, 1.3-3.2), and B/Yamagata (1.3; 95% CI, 1.0-1.8), but not for B/Victoria (0.9; 95% CI, 0.6-1.3). The effect did not vary significantly across the different age and BMI groups. By Day 180, titers did not differ significantly. Reactogenicity and safety profiles were similar between groups. CONCLUSIONS: In adults with severe obesity, RIV elicited stronger short-term humoral immune responses than an egg-based standard-dose vaccine, suggesting potential additional benefit for influenza prevention in this vulnerable population.

Humans

Whole-transcriptome RNA sequencing and ceRNA network analyses provide novel insights into the antibacterial immune response of Hippocampus abdominalis against Vibrio harveyi.

Long non-coding RNAs (lncRNAs) stand as newly-arisen molecular types that exert regulatory effects, able to operate as competitive endogenous RNAs (ceRNAs) to engage microRNAs (miRNAs) in interaction, resulting in the recovery of target mRNA expression and activity. Increasing evidences indicate that the ceRNA network affects various biological processes in mammals, including development, cellular differentiation, metabolism, immune response, and disease pathogenesis. In teleost fish, the lncRNA-miRNA-mRNA regulatory networks have been reported occasionally. However, up to now, the roles of lncRNAs in the big-belly seahorse (Hippocampus abdominalis) remains unclear. In this study, we reported for the first time, via whole-transcriptome RNA sequencing, the lncRNA mediated ceRNA regulatory network in Vibrio harveyi-infected H. abdominalis. A total of 4197 differentially expressed mRNAs (DE-mRNAs), 1317 DE-lncRNAs, and 183 DE-miRNAs were identified. Furthermore, the crosstalk between miRNAs and lncRNAs as well as between miRNAs and mRNAs was inferred based on the negative correlations between miRNAs and their target lncRNAs/mRNAs. A core immune associated lncRNA-miRNA-mRNA putative regulatory network was thus constructed, comprising 211 lncRNA-miRNA and 224 mRNA-miRNA pairs. In conclusion, our findings provide an integrative overview of the ceRNA regulatory networks on the underlying immune responses to V. harveyi infection in the big-belly seahorse, and offer a solid theoretical foundation for the comparative immunological research of teleost fish.

Animals

Rotavirus vaccine effectiveness against rotavirus and acute gastroenteritis mortality: an analysis of pooled case-control studies from the MNSSTER-V dataset.

BACKGROUND: Rotavirus accounts for an estimated 25% of diarrhoea deaths in children under 5 years globally, and more than 140 countries have included rotavirus vaccines in their routine national infant vaccination programmes. We aimed to calculate rotavirus vaccine effectiveness against rotavirus-positive and all-cause acute gastroenteritis deaths. METHODS: The Multi-National Subpopulations Study to Evaluate Rotavirus Vaccines (MNSSTER-V) dataset combines child-level data from test-negative case-control studies of rotavirus vaccine effectiveness that enrolled children under 5 years of age seeking care for acute gastroenteritis at hospitals or emergency departments in 24 countries between July 1, 2007, and Aug 24, 2023. Children were included in this study if they were: younger than 5 years, met the acute gastroenteritis case definition (had at least three episodes of diarrhoea in a 24-h period, had non-bloody and non-chronic diarrhoea, and were enrolled within 7 days of diarrhoea onset), met vaccine card quality metrics, had vaccine delivery dates if the child was reported to have received a rotavirus vaccine, and had a reported outcome of death or discharge. In-hospital acute gastroenteritis deaths were characterised, and rotavirus vaccine effectiveness against all-cause and rotavirus-positive acute gastroenteritis mortality was calculated using an unconditional logistic regression model with adjustment for national under-5 mortality strata and child's age. Vaccine effectiveness analyses against all-cause and rotavirus-positive acute gastroenteritis mortality were restricted to children aged at least 3 months who received any routine vaccines from countries reporting at least one acute gastroenteritis death. FINDINGS: From the MNSSTER-V dataset, we included 27&#x2008;252 children younger than 5 years enrolled from 22 countries; outcomes of patients were not available for two countries. At least one in-hospital acute gastroenteritis death was reported from 16 countries including 21&#x2008;522 children; in total, 183 all-cause acute gastroenteritis deaths and 25 rotavirus-positive deaths were reported. Among children aged at least 3 months who had received any routine vaccines, receiving at least one dose of a rotavirus vaccine had an adjusted vaccine effectiveness of 75&#xb7;8% (95% CI 28&#xb7;4 to 91&#xb7;8; n=13&#x2008;630) against rotavirus-positive acute gastroenteritis mortality and 20&#xb7;8% (-47&#xb7;0 to 57&#xb7;3; n=20&#x2008;005) against all-cause acute gastroenteritis mortality. INTERPRETATION: Rotavirus vaccines are effective in preventing rotavirus-positive acute gastroenteritis mortality. Continued efforts to improve vaccine delivery could help to reduce acute gastroenteritis mortality due to rotavirus worldwide. FUNDING: None.

Humans

Transcriptomic responses of gill and intestinal tissues in Nile tilapia (Oreochromis niloticus) to bacterial infection following sequential nanoimmersion and hydrogel-based multivalent vaccination.

Bacterial pathogens, including Flavobacterium oreochromis, Aeromonas veronii, Streptococcus agalactiae, and Edwardsiella tarda, represent major infectious threats to Nile tilapia (Oreochromis niloticus). A multivalent vaccination strategy integrating cationic nanoemulsion immersion with oral hydrogel boosters was developed to investigate tissue-specific immune responses at the transcriptomic level. Gill tissues were collected following immersion challenge and intestinal tissues following intraperitoneal injection challenge, reflecting the physiologically relevant infection biology of each pathogen and the mechanistic rationale of each delivery platform. RNA sequencing (RNA-seq) generated high-quality datasets (mapping rate&#xa0;>&#xa0;81.64%) with strong concordance to quantitative real-time PCR (qRT-PCR) validation (r&#xa0;=&#xa0;0.83). Comparative transcriptomic analysis revealed distinct yet complementary immune signatures between tissues. Gill transcriptomes were enriched in phagosome, focal adhesion, extracellular matrix-receptor interaction (ECM-receptor interaction), and cytokine-cytokine receptor interaction pathways, accompanied by increased expression of major histocompatibility complex class I/II (MHC class I/II), mannose receptor, &#x3b1;V&#x3b2;3 integrin, and calnexin, indicating innate activation, enhanced phagocytic capacity, epithelial barrier reinforcement, and adaptive immune coordination. Intestinal transcriptomes showed predominant enrichment of adaptive immune pathways, including the intestinal immune network for immunoglobulin (Ig) production, Forkhead box O (FoxO) signaling, and mitogen-activated protein kinase (MAPK) signaling, with increased expression of T-cell receptor (TCR), inducible T-cell co-stimulator ligand (ICOS-L), C-X-C chemokine receptor type 4 (CXCR4), and polymeric immunoglobulin receptor (pIgR), reflecting T and B cell coordination, lymphocyte trafficking, and mucosal immunoglobulin transport, alongside innate engagement through phagosome pathway enrichment. Shared upregulation of MHC class II, B-cell receptor (BCR) signaling, integrin alpha M (ITGAM), and immunoglobulin-associated components across both tissues suggests coordinated mucosal immune activation through a conserved immune module, warranting direct experimental validation. Collectively, these findings provide transcriptomic evidence that this vaccination strategy elicits an integrated, tissue-specialized immune response, advancing mechanistic understanding of gill and intestinal immunity in vaccine-induced protection of teleost fish.

Animals

Adherence and efficacy of the 0&#x2009;-&#x2009;7&#x2009;-&#x2009;21-day versus the 0&#x2009;-&#x2009;1&#x2009;-&#x2009;6-month hepatitis B vaccination schedules among people who use drugs: a two-year randomized controlled trial.

BACKGROUND: To compare the adherence and efficacy between the 0&#x2009;-&#x2009;7&#x2009;-&#x2009;21-day and the 0&#x2009;-&#x2009;1&#x2009;-&#x2009;6-month hepatitis B virus (HBV) vaccination schedules among people who use drugs (PWUD) in China. RESEARCH DESIGN AND METHODS: A randomized controlled trial was conducted in 1261 HBV-susceptible PWUD from compulsory isolated detoxification centers (CIDCs) and methadone maintenance treatment (MMT) clinics in Xi'an. A 20&#x2009;&#xb5;g per-dose vaccine was used. HBV surface antibody (anti-HBs), surface antigen, and core antibody were tested at months 7, 15, and 22 after the first dose. RESULTS: Third-dose coverage was significantly higher in the 0&#x2009;-&#x2009;7&#x2009;-&#x2009;21-day group (74.40%) than in the 0&#x2009;-&#x2009;1&#x2009;-&#x2009;6-month group (51.58%, p&#x2009;<&#x2009;0.001), mainly driven by participants from CIDCs (77.75% vs. 45.69%). Anti-HBs positive rates at months 7, 15, and 22 among participants who completed all three doses were significantly higher for the 0&#x2009;-&#x2009;1&#x2009;-&#x2009;6-month schedule (90.71%, 76.82%, and 67.35%) than for the 0&#x2009;-&#x2009;7&#x2009;-&#x2009;21-day schedule (74.23%, 49.40%, and 40.95%; all p&#x2009;<&#x2009;0.001). HBV infection incidence was similar between schedules, but significantly different between vaccinees and non-vaccinees (p&#x2009;=&#x2009;0.018). CONCLUSIONS: The 0&#x2009;-&#x2009;7&#x2009;-&#x2009;21-day schedule substantially enhances three-dose completion in PWUD, but induces a notably weaker anti-HBs response and persistence. Schedules should be selected based on the management models for PWUD and their individual characteristics. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900022403).

Humans

Characterization of the Immune Response after Oral Cholera Vaccination (OCV) and Effects of Mycophenolate Mofetil on Priming of this Immune Response-A Randomized, Placebo-Controlled Trial.

Mycophenolate mofetil (MMF) is an immunosuppressive drug widely used by solid organ transplant recipients. Although it is known that MMF suppresses immune responses, its exact effects on specific vaccinations have not been investigated yet. Mucosal vaccinations are increasingly used, such as a cholera vaccination consisting of two oral immunizations (oral cholera vaccination; OCV). This study aimed to investigate the specific immunosuppressive effects of MMF use during the first dose of OCV in a randomized, placebo-controlled trial in healthy volunteers. Moreover, the study aimed to characterize the immune response provoked by OCV in detail. This randomized, placebo-controlled, single-blind trial included 16 healthy volunteers, each receiving two doses of Dukoral&#xae; and an intranasal rechallenge. Outcome measures were serum antibody responses (IgA and IgG) and IgA levels in saliva. Additionally, peripheral blood mononuclear cells (PBMCs) of participants were investigated for ex&#xa0;vivo cytokine production and expression of tissue-specific homing markers after OCV. There were considerable serum IgA and IgG responses after vaccination. MMF-treated volunteers still showed a significant cholera antibody response, though data suggest a potential suppression by MMF without reaching statistical significance. There was no substantial IgA response in saliva. Investigation of PBMCs from OCV-treated participants showed a Th2 skewing with increased ex&#xa0;vivo production of TNF, IL-2, IL-5, IL-13, and IL-22 compared to the placebo group. Taken together, this study provides a framework for future clinical pharmacology studies building on OCV as a challenge model and for further investigation of specific effects of MMF on mucosal vaccination responses.

Humans