Vaccine Efficacy Research Articles

Ebola Outbreak Response in the DRC with rVSV-ZEBOV-GP Ring Vaccination

BackgroundAt the beginning of the 2018–2020 outbreak of Ebola virus disease (EVD) in eastern Democratic Republic of Congo (DRC), no vaccine had been licensed. However, cluster-randomized evidence from Guinea in 2015 had indicated that ring vaccination around new cases (targeting contacts and contacts-of-contacts) with the use of single-dose live-replicating rVSV-ZEBOV-GP vaccine reduced EVD rates starting 10 days after vaccination. Thus, ring vaccination was added to the standard control measures for that outbreak.MethodsIn this study, we evaluated the incidence of EVD within the first 9 days after vaccination (when little protection was expected from case isolation or ring vaccination), during days 10 to 29, and at later time periods. We established 1853 rings around new cases or clusters within 21 days after symptom onset in the index case and offered vaccination to the ring members. Vaccinees were monitored for EVD onset until the end of the outbreak in mid-2020.ResultsFrom August 8, 2018, to January 14, 2020, we vaccinated 265,183 participants. Of these vaccinees, 102,515 were monitored on days 0, 3, and 21 for safety. Among the contacts and contacts-of-contacts, 434 cases of EVD (0.2 per ring) were diagnosed, almost all within 0 to 9 days (380 cases) or 10 to 29 days (32 cases) after vaccination. An additional 22 cases were diagnosed after day 29 during an average of 170 more days of follow-up. The sooner that control measures (including ring vaccination) began after EVD onset in the index case, the sooner EVD rates fell among contacts. In each subgroup, EVD rates fell suddenly around day 10. Among the contacts and contacts-of-contacts who were still disease-free at day 10, the EVD onset rate during days 10 to 29 was 0.16 per 1000 (in 32 of 194,019 participants). This rate was much lower than the rate of 4.64 per 1000 (in 21 of 4528 participants) that had been seen among similarly defined ring members in Guinea, in whom standard control measures had been promptly initiated but vaccination was delayed until 21 days after ring formation (rate ratio, 0.04; 95% confidence interval, 0.02 to 0.06). No safety concerns with the vaccine were identified.ConclusionsNonrandomized evidence regarding standard EVD control measures plus ring vaccination in eastern DRC reinforces the earlier randomized evidence from Guinea of vaccine efficacy against EVD onset 10 or more days after vaccination.

Isolation of porcine epidemic diarrhea virus strain CHCQ-2023 from Chongqing Province and analysis of S gene recombination

BackgroundIn recent years, the prevalence and incidence of porcine epidemic diarrhea virus (PEDV) infection have been on the rise. The occurrence of multiviral infections and recombination mutations has led to accelerated viral evolution and reduced vaccine efficacy. In the present study, a PEDV strain was isolated from a pig farm (Chongqing Province, China) with an outbreak of porcine diarrhea, and its S gene was found to be recombinant.ResultsThe optimal trypsin concentration for blind passage of PEDV in Vero cells was determined to be 7.5 µg/mL. Following two blind passages of the virus in Vero cells, the virus was unable to adapt to the cells. Therefore, PEDV was blindly passaged in IPEC-J2 cells using the optimal concentration of trypsin (5 µg/mL). Next, a series of characterization experiments were performed. Recombination analyses of the isolates using software revealed that the S gene of strain CHCQ-2023 was derived from the primary parent strain PEDV-1 C and secondary parent strain SQ2014, with recombination occurring at a 3152 bp breakpoint. Furthermore, a specific B-cell antigenic epitope was predicted on the S2 subunit of the S protein.ConclusionA PEDV strain was isolated and characterized, and its S gene was characterized. The findings provide a bioinformatic basis for the study of PEDV strain variation due to genetic recombination.

Economic evaluation of childhood pneumococcal conjugate vaccination programs in Qinghai and Hainan provinces, China

ABSTRACT Background The burden of pneumococcal disease varies regionally in China, particularly affecting children in Qinghai and Hainan. Nevertheless, absence of pneumococcal conjugate vaccine (PCV) in the National Immunization Program (NIP) or local programs presents limited coverage. This study evaluated the health and economic impact of including PCV in immunization programs in Qinghai and Hainan. Research design and methods A decision tree Markov model was constructed to simulate health outcomes and lifetime costs among children under different 13-valent PCV (PCV13) vaccination strategies compared to current practices, from societal and healthcare perspectives. Data on epidemiology, vaccine efficacy, cost, and utility were obtained from literature or open databases. Sensitivity analyses were conducted to explore parameter uncertainty. Results Including three-dose PCV13 in provincial programs at NIP coverage (98.91%) could avert 7100 episodes and 118 deaths in Qinghai, and 6200 episodes and 66 deaths in Hainan. It was cost-effective at the $68.2/dose in private market and cost-saving at the United Nations Children’s Fund (UNICEF) recommended $25/dose for both provinces. Increasing coverage to 50% or 75% was also cost-effective. Sensitivity analyses confirmed results robustness despite parameter uncertainty. Conclusions Prioritizing PCV13 in immunization programs in Qinghai and Hainan could effectively reduce disease burden, improve population health, and promote health equity.

Modeling of randomized hepatitis C vaccine trials: Bridging the gap between controlled human infection models and real-word testing

Abstract Global elimination of chronic hepatitis C (CHC) remains difficult without an effective vaccine. Since injection drug use is the leading cause of hepatitis C virus (HCV) transmission in Western Europe and North America, people who inject drugs (PWID) are an important population for testing HCV vaccine effectiveness in randomized-clinical trials (RCTs). However, RCTs in PWID are inherently challenging. To accelerate vaccine development, controlled human infection (CHI) models have been suggested as a means to identify effective vaccines. To bridge the gap between CHI models and real-world testing, we developed an agent-based model simulating a two-dose vaccine to prevent CHC in PWID, representing 32,000 PWID in metropolitan Chicago and accounting for networks and HCV infections. We ran 500 trial simulations under 50% and 75% assumed-vaccine efficacy (aVE) and sampled HCV infection status of recruited in silico PWID. The mean estimated vaccine efficacy (eVE) for 50% and 75% aVE was 48% (standard deviation (SD ±12) and 72% (SD±11), respectively. For both conditions, the majority of trials (∼71%) resulted in eVEs within 1SD of the mean, demonstrating a robust trial design. Trials that resulted in eVEs >1SD from the mean (lowest eVEs of 3% and 35% for 50% and 75% aVE, respectively), were more likely to have imbalances in acute infection rates across trial arms. Modeling indicates robust trial design and high success rates of finding vaccines to be effective in real-life trials in PWID. However, with less effective vaccines (aVEs∼50%) there remains a higher risk of concluding poor vaccine efficacy due to post-randomization imbalances.

Revitalizing tetanus vaccine literacy post road accidents: a comprehensive examination of knowledge and awareness initiative among non-medical university students in Lahore, Pakistan

IntroductionTetanus, caused by Clostridium tetani, poses a life-threatening risk by affecting the nervous system and inducing muscle tightness. The objective of this study is to examine the knowledge, attitudes, and behaviors of non-medical university students regarding the tetanus vaccine in the context of post-road accidents.MethodsA descriptive cross-sectional study was conducted in 2023, involving 378 students from non-medical disciplines, primarily from information technology, business administration, and engineering faculties, with a mean age of 20.7 years. The sample size was calculated using the Raosoft sample calculator, and participants were selected via consecutive random sampling. Data was collected through a structured, self-administered questionnaire and analyzed using SPSS 22.0.ResultsGender distribution was 51.6% female and 48.4% male. Out of the 378 students, 53.4% (p=0.003) were unaware of tetanus contraction sources, 52.8% (p=0.004) lacked knowledge of its symptoms and 68.3% (p=0.004) were unfamiliar with the total number of doses. An appreciable 88.9% (p0.063) are willing to receive post-accident tetanus vaccination, reflecting positive attitudes and openness to preventive measures. Similarly, the p-values >0.05 show no gender disparity in willingness to receive tetanus vaccination (p=0.063) and recommending vaccination to others after a road accident (p=0.879).ConclusionsNotwithstanding participants' positive attitudes, the results indicate poor knowledge of tetanus regarding its transmission, symptoms, and doses. Interventions should focus on refining practical aspects of education, including symptom recognition, vaccine efficacy, duration, and the importance of sustaining immunity.

A newly developed oral infection mouse model of shigellosis for immunogenicity and protective efficacy studies of a candidate vaccine.

Shigella infection poses a significant public health challenge in the developing world. However, lack of a widely available mouse model that replicates human shigellosis creates a major bottleneck to better understanding of disease pathogenesis and development of newer drugs and vaccines. BALB/c mice pre-treated with streptomycin and iron (FeCl3) plus desferrioxamine intraperitoneally followed by oral infection with virulent Shigella flexneri 2a resulted in diarrhea, loss of body weight, bacterial colonization and progressive colitis characterized by disruption of epithelial lining, loss of crypt architecture with goblet cell depletion, increased polymorphonuclear infiltration into the mucosa, submucosal swelling (edema), and raised proinflammatory cytokines and chemokines in the large intestine. To evaluate the usefulness of the model for vaccine efficacy studies, mice were immunized intranasally with a recombinant protein vaccine containing Shigella invasion protein invasion plasmid antigen B (IpaB). Vaccinated mice conferred protection against Shigella, indicating that the model is suitable for testing of vaccine candidates. To protect both Shigella and Salmonella, a chimeric recombinant vaccine (rIpaB-T2544) was developed by fusing IpaB with Salmonella outer membrane protein T2544. Vaccinated mice developed antigen-specific serum IgG and IgA antibodies and a balanced Th1/Th2 response and were protected against oral challenge with Shigella (S. flexneri 2a, Shigella dysenteriae, and Shigella sonnei) using our present mouse model and Salmonella (Salmonella Typhi and Paratyphi) using an iron overload mouse model. We describe here the development of an oral Shigella infection model in wild-type mouse. This model was successfully used to demonstrate the immunogenicity and protective efficacy of a candidate protein subunit vaccine against Shigella.

Vaccination for solid organ transplanted patients: Recommendations, efficacy, and safety.

Solid organ transplant recipients face unique challenges in managing their immunosuppressed status, making vaccination a critical consideration. This review aimed to comprehensively analyze current recommendations, evaluate the efficacy of vaccinations in this population, and assess safety concerns. We explored the latest evidence on vaccine types, timing, and potential benefits for transplant patients, highlighting the importance of individualized approaches for routinely used vaccines as well as coronavirus disease 2019 vaccines. By synthesizing available data, this review underscored the pressing need to optimize vaccination strategies, ensuring that transplant recipients can obtain the full protection against many pathogens while minimizing risks associated with their post-transplant immunosuppression.

Diversity in Naturally Acquired Immunity to Group B Streptococcus: A Comparative Study of Women from Bangladesh, Malawi, and the United Kingdom.

Significant disparities in Group B Streptococcus (GBS) colonisation and neonatal disease rates have been documented across different geographical regions. For example, Bangladesh reports notably lower rates compared to the United Kingdom (UK) and Malawi. This study investigates whether this epidemiological variability correlates with the immune response to GBS in these regions. Qualitative and quantitative analyses of naturally acquired immunoglobulin G (IgG) antibodies against GBS capsular polysaccharides (CPS) and the Alp protein family were conducted in serum samples from women of childbearing age in the UK, Bangladesh, and Malawi. The efficacy of these antibodies in clearing vaginal colonisation or protecting newborns from GBS infection was assessed using humanised mouse models. Bangladeshi women displayed the highest diversity in serotype distribution, with elevated immunoglobulin G (IgG) levels in the serum against GBS capsular polysaccharides (CPS)- Ia, Ib, II, III, IV, and V, as well as Alp family proteins. In contrast, Malawian sera demonstrated the weakest antibody response. Bangladeshi sera also showed heightened IgG-mediated complement deposition, opsonophagocytic killing and neonatal Fc receptor (FcRn)-binding while tested against CPS Ib. In a humanised FcRn mouse model, Bangladeshi sera led to faster clearance of GBS virulent serotype Ib vaginal colonisation. Additionally, offspring from dams passively immunised with Bangladeshi sera demonstrated notably increased survival rates. This study demonstrates significant variability in the immune response to GBS across different geographical regions. These findings underscore the importance of understanding GBS-induced immune response in diverse populations, which may significantly impact vaccine efficacy in these regions.

Glucocorticoid dosing and implications for vaccination: Evolution of global definitions.

Despite widespread adoption of "high-dose" glucocorticoid definitions across international immunisation guidelines (i.e., prednisone-equivalent dosing >20 mg/day, or >2 mg/kg/day in children), the rationale remains unclear. Literature searches were performed through academic databases for this narrative review to identify relevant evidence regarding glucocorticoid dosing on vaccine responses and safety. In people receiving prednisone <7 mg/day, vaccine responses are maintained. In people on 'high-dose' glucocorticoids (>20 mg/day), antibody titres and seropositivity are reduced, whereas the impact of low- to medium-dose glucocorticoids (7 to 20 mg/day) on vaccine efficacy remains inconclusive. Due to inconsistent paediatric dosing regimens, data is insufficient to support a unified "high-dose" glucocorticoid threshold. Non-live vaccines are well tolerated in patients receiving glucocorticoids with rheumatic/inflammatory disorders, but enhanced reactogenicity after live vaccination may occur in those with severe immunodeficiencies. Clinicians should consider individual risk-benefit profiles, rather than following strict dosing thresholds, when curating immunisation programs for patients prescribed glucocorticoids.

Evaluating artesunate monotherapy and dihydroartemisinin-piperaquine as potential antimalarial options for prevaccination radical cures during future malaria vaccine field efficacy trials

BackgroundIn malaria vaccine clinical trials, immune responses after vaccination may be compromised due to immunosuppression caused by concurrent Plasmodium falciparum infection. This has a direct effect on the protective efficacy of the vaccine being evaluated. Therefore, parasite clearance prior to vaccination is being considered. Drugs with good safety and efficacy profiles and a short posttreatment prophylaxis period should be used. Two antimalarial drugs, artesunate (AS) as monotherapy and dihydroartemisinin-piperaquine (DHAPQ), have been evaluated in order to identify the most suitable option for use in future trials.MethodsA cohort of children aged 1.5–12 years living in the Banfora Health District area was recruited. They were randomly assigned to receive supervised curative doses of AS monotherapy for 7 days or DHAPQ for 3 days. A polymerase chain reaction (PCR) was performed 21 days after treatment to confirm clearance of infection, and only those with a negative PCR were included in the study cohort for a 6-month longitudinal follow-up. Cohort children were actively visited fortnightly to collect blood samples for P. falciparum detection via microscopy and PCR. Passive surveillance was also conducted at the local health facility to record incident malaria episodes that occurred between two active visits.ResultsA total of 513 children were treated. Among these patients, 458 (89.3%) were free of P. falciparum malaria infection on day 21: 87.3% (226/259) in the AS group vs 91.3% (232/254) in the DHAPQ group (p = 0.053). The mean time to first malaria infection by microscopy was 154.9 (2.9) days in the DHAPQ arm and 129.0 (3.9) days in the AS arm (p < 0.01). The incidence rates of clinical malaria episodes during the follow-up period were 0.507 (0.369–0.645) and 0.293 (0.190–0.397) in the AS and DHAPQ arms, respectively (p < 0.05).ConclusionsThese findings suggest that although both drugs are effective in clearing P. falciparum infections, AS is likely to cause no more than minimal interference with the evaluation of vaccine efficacy endpoints and could, therefore, be considered for use.Trial registration: NCT04601714.

Retrospective Analysis of HLA Class II-Restricted Neoantigen Peptide-Pulsed Dendritic Cell Vaccine for Breast Cancer

Background/Objectives: Neoantigens have attracted attention as ideal therapeutic targets for anti-tumour immunotherapy because the T cells that respond to neoantigens are not affected by central immune tolerance. Recent findings have revealed that the activation of CD4-positive T cells plays a central role in antitumor immunity, and thus targeting human leukocyte antigen (HLA) class II-restricted neoantigens, which are targets of CD4-positive T cells, is of significance. However, there are very few detailed reports of neoantigen vaccine therapies that use an HLA class II-restricted long peptide. In the present study, we retrospectively analysed the ability of HLA class II-restricted neoantigen-pulsed dendritic cell vaccines to induce immune response in five breast cancer patients. Methods: We performed whole exome and RNA sequencing of breast cancer tissues and neoantigen prediction using an in silico pipeline. We then administered dendritic cells pulsed with synthesized an HLA class II-restricted long peptide containing an epitope with high affinity to HLA class I in the lymph node. Results: ELISPOT analysis confirmed that a T-cell response specific for the HLA class II-restricted neoantigen was induced in all cases. TCR repertoire analysis of peripheral blood mononuclear cells before and after treatment in three patients showed increases of specific T-cell clones in two of the three patients. Importantly, no recurrence was observed in all patients. Conclusions: Our analysis demonstrated the immunological efficacy of the HLA class II-restricted neoantigen peptide dendritic cell vaccine against breast cancer and provides useful information for the development of neoantigen vaccine therapy for breast cancer.

Comparison of the Efficacy of Mycoplasma gallisepticum Vaccine Programs in Chickens

ABSTRACT The efficacy of two Mycoplasma gallisepticum commercially available vaccines administered singly or in combination was evaluated in two trials; in both trials, specific-pathogen-free (SPF) chickens were vaccinated with the live attenuated F-strain vaccine at 5 weeks of age (WOA), an inactivated M. gallisepticum bacterin at 9 and 13 WOA, or both vaccines. In the first trial, groups of vaccinated birds, along with controls, were challenged via aerosol with virulent R-strain at 22 and 41 weeks of age. All of the vaccine programs evaluated showed a statistically significant reduction in colonization with the challenge strain following challenge at either timepoint. However, only the programs including the live vaccine also showed significant protection from respiratory lesions and ovarian regression; and although there were numerical differences indicating benefits of a combined (live + bacterin) program, the addition of bacterins did not enhance (or reduce) the efficacy of the F-strain vaccine in a statistically significant manner (P ≤ 0.05). In the second trial, groups of vaccinated birds, along with controls, were challenged via aerosol with different doses of virulent M. gallisepticum R-strain at 17 weeks of age. Both vaccination programs in this trial (live only and live + bacterin) resulted in significant protection against challenge strain colonization and air sac lesions (P ≤ 0.05); In addition, the live + bacterin program showed significantly improved results with respect to colonization with the challenge strain as well as protection from air sac lesions compared to the live vaccine alone (P ≤ 0.05).

Is a Consensus Case Definition for Viral Associated Lower Respiratory Tract Disease (LRTD) in Clinical Trials Possible?

Lower respiratory tract illness or disease (LRTI/LRTD) represents a significant source of morbidity and mortality following viral respiratory illnesses, yet a consensus definition for this outcome is lacking. Recent studies of novel vaccines against respiratory syncytial virus (RSV) for older adults used LRTI/LRTD as the primary outcome to assess vaccine efficacy. However, the different vaccine trials have used highly variable criteria to define this outcome, leading to difficulty in comparison of vaccine efficacy results between trials. Here we review the key differences in criteria for case definitions, highlight strategies to best approximate compatibility between definitions, and review vaccine efficacy results among currently US Food and Drug Administration (FDA)-approved vaccines using these strategies. We hope this overview will support the need to develop a consensus definition for LRTI/LRTD to improve future research related to viral respiratory disease.

Beyond prevention: in silico designing a one-two punch novel therapeutic vaccine candidate against major oncoproteins of HPV 16, 18, 31, and 45 and subsequent cervical cancer

ABSTRACT The human papillomavirus (HPV) is the most prevalent viral sexually transmitted disease (STD). HPV 16, 18, 31 and 45 are most associated with the development of cervical cancer. Currently approved HPV vaccines are only preventive and have no therapeutic activity. With immunoinformatics approaches, we tried to design a novel vaccine against E6 and E7 oncoproteins of HPV 16, 18, 31 and 45 for the prevention and treatment of cervical cancer. The tertiary structure of the vaccine was modelled and validated. The vaccine was docked with TLR4 and TLR9 receptors, which have an undeniable anti-tumour immunity against cervical cancer. Molecular dynamic simulation indicates that the vaccine-TLR complexes were structurally stable. Immune stimulation and population coverage analysis results were much better than similar studies. Our new multi-epitope vaccine is the first HPV vaccine to target the E6 and E7 antigens of HPV 16, 18, 31 and 45. Also, this is the first study to target conserved regions of HPV and then merge the T and B cell epitopes as a regional epitope, which increases vaccine efficacy and reliability. We hope that the methodology of this study will even shed light on the design of vaccines against other viral STDs.

Enhancing COVID-19 Vaccine Efficacy: Dual Adjuvant Strategies with TLR7/8 Agonists and Glycolipids.

The controlled release of immunostimulatory agents represents a promising strategy to enhance vaccine efficacy while minimizing side effects. This study aimed to improve the efficacy of the RBD-Fc-based COVID-19 vaccine through combining of an iNKT cell agonist and a TLR7/8 agonist using covalent conjugation and temporal delivery. We hypothesized that these combinations would yield a more balanced Th1/Th2 immune response. For covalent conjugation, we employed an uncleavable linker and a self-immolative disulfide linker to conjugate α-galactosylceramide (αGC) to imidazoquinoline (IMDQ). The αGC-SS-IMDQ-Ac conjugate, designed with a prodrug strategy for controlled TLR7/8 agonist release, elicited a higher IFN-γ/IL-4 T cell response ratio than individual adjuvants or their admixture. In the temporal delivery approach, administering IMDQ followed by αGC after 2 h resulted in the highest IgG2a/IgG1 ratio, significantly surpassing other groups. A 6 h delay between glycolipid and IMDQ injections yielded balanced IgG responses, enhancing IgG, IgG1, and IgG2a levels synergistically.

The antitumor activity of TGFβ-specific T cells is dependent on IL-6 signaling.

Although interleukin (IL)-6 is considered immunosuppressive and tumor-promoting, emerging evidence suggests that it may support antitumor immunity. While combining immune checkpoint inhibitors (ICIs) and radiotherapy in patients with pancreatic cancer (PC) has yielded promising clinical results, the addition of an anti-IL-6 receptor (IL-6R) antibody has failed to elicit clinical benefits. Notably, a robust TGFβ-specific immune response at baseline in PC patients treated solely with ICIs and radiotherapy correlated with improved survival. Recent preclinical studies demonstrated the efficacy of a TGFβ-based immune modulatory vaccine in controlling PC tumor growth, underscoring the important role of TGFβ-specific immunity in PC. Here, we explored the importance of IL-6 for TGFβ-specific immunity in PC. In a murine model of PC, coadministration of the TGFβ-based immune modulatory vaccine with an anti-IL-6R antibody rendered the vaccine ineffective. IL-6R blockade hampered the development of vaccine-induced T-cells and tumoral T-cell infiltration. Furthermore, it impaired the myeloid population, resulting in increased tumor-associated macrophage infiltration and an enhanced immunosuppressive phenotype. In PC patients, in contrast to those receiving only ICIs and radiotherapy, robust TGFβ-specific T-cell responses at baseline did not correlate with improved survival in patients receiving ICIs, radiotherapy and IL-6R blockade. Peripheral blood immunophenotyping revealed that IL-6R blockade altered the T-cell and monocytic compartments, which was consistent with the findings in the murine model. Our data suggest that the antitumor efficacy of TGFβ-specific T cells in PC depends on the presence of IL-6 within the tumor. Consequently, caution should be exercised when employing IL-6R blockade in patients receiving cancer immunotherapy.

Vaccination of pregnant women: an overview of European policies and strategies to promote it

Maternal immunization is a valuable tool for protecting mother and unborn child from vaccine-preventable diseases. However, the implementation of strategies for vaccinating pregnant women has only recently gained traction. This work is aimed at providing an overview of European vaccination strategies and gathering evidence on interventions enhancing vaccination knowledge, attitudes, and behaviors (KAB) in pregnant women. To summarize current pregnancy vaccination strategies in Europe, we consulted literature, institutional national health system websites, and the ECDC Vaccine Scheduler. The review of evidence on interventions targeting pregnant women’s vaccination KAB was performed by searching primary studies on PubMed and Web of Science. The 27 EU member states offer various vaccinations in pregnancy, but only 10 recommend all of these: tetanus, pertussis, diphtheria, influenza, and COVID-19, albeit with different administration schedules. The literature review included 7 studies, 3 from Italy and 4 from other European countries (UK, Netherlands, Greece, Poland, and Ukraine). They were conducted in various settings such as childbirth preparation courses, prenatal visits, and online platforms, and all included educational interventions providing information on vaccine safety and efficacy during pregnancy. Knowledge about vaccines and vaccine-preventable diseases, generally low in the pre-intervention period, increased post-intervention, with a rise in awareness of the risks associated with infectious diseases and the recommended vaccines, a reduction in vaccine-related misinformation, and a greater propensity to vaccinate both newborns and themselves. Furthermore, there was a significant increase in adherence to recommended vaccinations, particularly among those with higher educational levels. However, vaccine hesitancy persisted, influenced by factors such as fear of adverse events and the lack of recommendations from healthcare providers. Variations in pregnancy vaccination strategies across Europe emphasize the importance of establishing a unified framework to optimize maternal and fetal health outcomes through evidence-based policies. Educational interventions may positively impact pregnant women’s KAB, therefore promoting vaccination uptake.

Diverse immune cell profiles in ASFV-associated lymphopenia

Pathogenic African swine fever virus (ASFV) remains a lethal causative agent in the domestic pig industry, which poses a burden on the swine market and causes substantial socioeconomic losses worldwide. Currently, there are no commercially efficacious vaccines or specific treatments available for ASF prevention and control. Unfortunately, little is known about the swine immune response upon ASFV infection. Here, we investigated the host immune response discrepancy induced by the field moderately virulent strain ASFV HB-2208 among healthy, diseased and asymptomatic pigs. In the peripheral blood of diseased swine, lymphopenia is caused by the massive loss of bystander lymphocytes, such as γδ T cells, B cells and CD4+ T cells. Conversely, ASFV has a strong tropism for the mononuclear phagocyte system (MPS) and partial dendritic cells (DCs), whose antigen-presenting ability is impeded by the downregulation of CD80 and MHC I. However, no significant difference in the number of CD8αhigh T cells was detected, whereas the frequencies of NK cells, NKT cells, and regulatory T cells (Tregs) were significantly increased. Additionally, an in vitro model was established with a coculture of primary pulmonary alveolar macrophages (PAMs) and peripheral blood mononuclear cells (PBMCs), which significantly reduced γδ T cells, B cells and CD4+ T cells and increased Tregs. The differentiated immune response might aid in enhancing the understanding of ASFV pathogenesis in suids and provide insights into the mechanism of ASFV-induced lymphopenia for further studies.

Development of a New Vaccine Adjuvant System Based on the Combination of the Synthetic TLR4 Agonist FP20 and a Synthetic QS-21 Variant.

In this study, we formulated an alternative to AS01b by combining FP20, a synthetic TLR4 agonist, and QS21v, a minimal saponin adjuvant, aiming to improve the vaccine efficacy and stability. The phase transition temperature of FP20 was determined by using differential scanning calorimetry to be 43.9 °C, providing a foundation for the formulation process. The coformulation was prepared using a dry film method for even adjuvant distribution. Characterization by dynamic light scattering and nanoparticle tracking analysis revealed a uniform particle size distribution of ∼120 nm. Cryogenic electron microscopy (CryoEM) revealed nanosized interactions between FP20 and QS21v, forming stable structures that likely enhanced the antigen presentation and immune activation. These physicochemical properties contributed to a robust in vivo synergy, where the coformulation elicited significantly higher antigen-specific antibody titers compared to individual adjuvants. These findings suggest that the FP20+QS21v coformulation provides a potent, stable, and safer alternative to traditional adjuvants, enhancing both vaccine efficacy and immunogenicity.

Mn and Zn-Doped Multivariate Metal-Organic Framework as a Metalloimmunological Adjuvant to Promote Protection Against Tuberculosis Infection.

A first-in-class vaccine adjuvant delivery system, Mn-ZIF, is developed by incorporating manganese (Mn) into the zinc-containing zeolitic-imidazolate framework-8 (ZIF-8). The mixed metal approach, which allowed for tunable Mn doping, is made possible by including a mild reducing agent in the reaction mixture. This approach allows up to 50% Mn, with the remaining 50% Zn within the ZIF. This multivariate approach exhibits significantly decreased cytotoxicity compared to ZIF-8. The porous structure of Mn-ZIF enables the co-delivery of the STING agonist cyclic di-adenosine monophosphate (CDA) through post-synthetic loading, forming CDA@Mn-ZIF. The composite demonstrated enhanced cellular uptake and synergistic activation of the cGAS-STING pathway, producing proinflammatory cytokines and activating antigen-presenting cells (APCs). In a preclinical Mycobacterium tuberculosis (Mtb) model, CDA@Mn-ZIF formulates with the CysVac2 fusion protein elicited a potent antigen-specific T-cell response and significantly reduced the mycobacterial burden in the lungs of infected mice. These findings highlight the potential of CDA@Mn-ZIF as a promising adjuvant for subunit vaccines, offering a novel approach to enhancing vaccine efficacy and protection against infectious diseases such as tuberculosis.