Adjuvanted Vaccine Research Articles

Cost-effectiveness of respiratory syncytial virus adjuvanted vaccine in Portuguese aged ≥ 60 years

Abstract Background Respiratory syncytial virus (RSV) infections are one of the leading causes of lower respiratory tract disease among adults aged ≥60 years in Europe. This study aims to assess the potential public health impact of the RSVPreF3 OA adjuvanted vaccine, the first approved preventive intervention for the older adult population in Portugal. Methods A monthly-cycle static Markov model was developed to assess RSVPreF3 OA adjuvanted vaccine impact on adults aged 60 years and older in Portugal. A single dose of RSVPreF3 OA adjuvanted vaccine was compared to no-vaccination over a three-year time-horizon. The model captures lower respiratory tract disease (LRTD) RSV cases, hospitalizations, deaths, and healthcare resource utilization. Data inputs were based on local published literature, supplemented by the best available data when local information was lacking. Results Based on preliminary analysis considering 75% vaccine coverage, model outputs estimate that RSVPreF3 OA adjuvanted vaccine can prevent 71,433 LRTD cases requiring medical attendance, 11,067 hospitalizations, 1,793 intensive care unit admissions and 1,003 deaths. The model estimates that 32 adults need to be vaccinated to avoid one RSV LRTD case, 207 adults need to be vaccinated to avoid one hospitalization and 2,283 adults need to be vaccinated to avoid one death. The incremental cost-effectiveness ratio was estimated at 9,541€, hence the RSVPreF3 OA adjuvanted vaccine is cost-effective compared to no vaccination. Conclusions The results demonstrate a strong preventive impact of the RSVPreF3 OA adjuvanted vaccine on health outcomes and healthcare resource utilization in adults ≥60 years, leading to a significant public health benefit. This result emphasizes the importance of preventing RSV to preserve the health and well-being of Portugal’s older adults. In addition, data from ongoing studies may enhance precision and extensive sensitivity analyses validate the robustness of the model’s input assumptions. Key messages • This study shows the robust evidence of RSVPreF3 OA adjuvanted vaccine to improve public health by preventing thousands of hospitalizations and deaths among ≥60 years, in Portugal. • Vaccinating adults aged ≥ 60 years with RSVPreF3 OA adjuvanted vaccine in Portugal is a cost-effective strategy.

The role of sociodemographic factors on herpes zoster vaccine uptake among hard-to-reach populations

Abstract Background The anti-Herpes Zoster (HZ) vaccination program was expanded with the adjuvated recombinant vaccine (HZR) in the Lazio Region, Italy, in 2022, restricting its use only to certain categories at risk due to pathological conditions, such as dialysis patients or immunocompromised individuals. This study focuses on the role of clinical and socio-demographic factors on HZR vaccine uptake within the fragile resident population of the Local Health Authority Rome 2 (ASL RM2). Methods This population-based, retrospective cohort study leveraged data from various registries and databases. The study population comprised 835,779 individuals aged ≥18 years who were both RM2 residents and registered with an RM2 general practitioner (GP). Among these, 143,242 individuals with at least one chronic condition were assessed for vaccination uptake using a multivariate logistic model, exploring associations with gender, age, nationality, marital status, household size, and level of deprivation. Results At the conclusion of the study period, a small fraction (1.5%) of the fragile subjects had received at least one dose of the HZR vaccine, and a majority (78%) completed the vaccination course of two doses. The analysis indicated that vaccine adherence was significantly higher in males (OR = 1.15) and individuals aged 65 + (OR = 1.13) while lower among residents in areas of medium (OR = 0.61) and high deprivation (OR = 0.44) and with specific living arrangements - widowed people living alone (OR = 0.66) and families ≥ 6 people (OR = 0.63). Conclusions The ASL RM2 vaccination strategy for hard-to-reach individuals includes an integrated approach, with the engagement of local healthcare facilities and hospitals. Despite these efforts, lower adherence in socioeconomically disadvantaged fragile patients suggests a pressing need for targeted communication strategies and interventions to ensure equitable access to the HZ vaccine, as these groups are more vulnerable to developing chronic diseases. Key messages • Socio-demographic factors significantly influence Herpes Zoster vaccine uptake in hard-to-reach populations, with lower adherence in socially deprived groups. • Tailored, equity-driven approaches are essential for enhancing vaccine coverage among hard-to-reach fragile individuals, mitigating the higher disease risks in these communities.

Immunogenicity and Safety of the Recombinant Adjuvanted Herpes Zoster Vaccine in Patients with Chronic Lymphocytic Leukemia and Multiple Myeloma

Background/objectives: Patients with chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are susceptible to viral infections, including varicella-zoster virus (VZV) reactivation due to both disease-related and treatment-induced immunosuppression. The recombinant adjuvanted herpes zoster vaccine (RZV) has shown high efficacy in immunocompetent adults, but immunogenicity data in CLL and MM patients are limited. This study evaluates the immunogenicity and safety of RZV in this population. Methods: Patients with CLL and MM vaccinated with RZV (administered in two doses at least one month apart) were included in the study. Pre- and post-vaccination anti-VZV IgM and IgG antibody levels were measured to assess immunogenicity, and adverse events (AEs) were captured for safety evaluation. Results: Seventy-eight patients received both vaccine doses, and 71 had post-vaccination samples. Most of the patients were IgM seronegative and IgG seropositive before vaccination. Pre-vaccination IgG levels were higher in CLL patients compared to MM patients (p = 0.001), while post-vaccination IgG levels significantly increased in both CLL (p < 0.0001) and MM (p < 0.0001) patients. In actively treated CLL patients, pre-vaccination IgG levels were significantly lower than in not actively treated patients (p = 0.002). Post-vaccination IgG levels were lower in MM patients receiving antiviral prophylaxis concurrently with the vaccination (p = 0.013). AEs were reported in 49.4% of patients after the first dose and 48.7% after the second dose, mostly mild (local or low-grade systemic). One case of immune thrombocytopenia was noted. Conclusions: RZV demonstrated strong immunogenicity and acceptable safety in CLL and MM patients, significantly boosting IgG levels, even in actively treated or heavily pretreated patients.

Fight the Flu: Protect Yourself and Others

As flu season approaches, it's crucial to take steps to protect yourself and those around you. The flu, a contagious respiratory illness caused by the influenza virus, can lead to severe complications, especially in young children, the elderly, and those with weakened immune systems. The best defense against the flu is vaccination. Flu vaccines are updated yearly to match circulating strains, reducing your chances of getting sick. Even if you catch the flu, the vaccine can lessen the severity of symptoms and prevent hospitalization. Different types of vaccines, such as standard-dose, high-dose, and adjuvanted vaccines, are tailored for various age groups, including children, adults, and seniors. In addition to vaccination, practicing good hygiene, like frequent handwashing, covering coughs, and staying home if sick, plays a crucial role in flu prevention. Together, these strategies form a strong defense against the flu, safeguarding communities during flu season.

Vaccination against respiratory syncytial virus (RSV)-For the protection of infants and older adults

Respiratory syncytial virus (RSV) is afrequent cause of respiratory infections in all age groups. Infections in infants and older adults frequently result in severe disease and complications. There is no specific antiviral treatment against RSV. The characterization of the structure of the fusion (F) protein in its immunogenic prefusion conformation has enabled the development of novel vaccines directed against the prefusion protein as the antigen. These include an adjuvanted monovalent vaccine (Arexvy) and anonadjuvanted bivalent vaccine (Abrysvo). Both are approved and indicated for use in older adults, in whom they have been shown to be over 80% effective in the protection against symptomatic RSV infections and associated lower respiratory tract diseases. Abrysvo is approved for use in pregnancy to protect the newborn through the transplacental transfer of high-titer maternal antibodies. The vaccine has been shown to have an efficacy of over 80% in the first 3 months of life to protect the infant from severe RSV-associated lower respiratory disease but slightly deceases after an age of 6 months. The clinical studies demonstrated the safety of the vaccines in both adults and pregnant women. The rate of undesired side effects was low in all studies and severe side effects were very rare. The new vaccines are efficacious new tools to prevent RSV-associated disease and complications in high-risk groups. For infants, an alternative strategy can be passive immunization with monoclonal antibodies, including the recently developed nirsevimab, which has also shown high efficacy.

Immunogenicity to Herpes Zoster recombinant subunit vaccine in immune-mediated rheumatic patients under treatment with JAK inhibitors.

Patients with immune-mediated rheumatic diseases (IMRDs) face an elevated risk of varicella-zoster virus infection (VZV), and herpes zoster (HZ). Treatment with immunosuppressors further increases the risk. A new recently approved adjuvant recombinant inactive vaccine, offers safe protection against HZ. However, limited data exist on the efficacy of this new vaccine in patients with IMRDs treated with JAK inhibitors. We aimed to characterize B cell and T cell immune responses elicited by the HZ recombinant subunit vaccine in patients with IMRDs under treatment with JAK inhibitors, and to identify factors that might be associated with reduced immunogenicity, and therefore reduced protection. We investigated humoral, and cellular CD4 and CD8 immune responses following a two-dose regimen of the recombinant inactive vaccine in 43 patients with rheumatic diseases treated with different JAK inhibitors. The responses were compared with age, gender and disease-matched healthy controls. Patients with IMRDs treated with JAK inhibitors showed reduced seroconversion rate (63% vs 100% and lower VZV IgG titers (1222 ± 411 vs 3048 ± 556, p< 0.0001) as compared with healthy controls. Functional T CD4 (IL-2 plus IFN-γ secretion) and T CD8 (Granzyme A and/or Granzyme B secretion) immune responses were also significantly diminished in IMRDs patients. Negative correlation was found between VZV antibody titers and age, specific treatments (baricitinib, tofacitinib, upadacitinib), cumulative methotrexate and glucocorticoid doses, history of multiple DMARDs, and treatment duration with JAK inhibitors. Functional T-CD4 responses but not functional T-CD8 responses also showed similar negative correlations. Positive associations were observed between functional T-CD4 and T-CD8 responses. Our study provides valuable insights into the immune responses elicited by the recombinant inactive vaccine in patients with IMRDs treated with JAK inhibitors. In these patients we have observed a broad impact on the adaptive humoral and cellular immune responses, suggesting a potential reduction in protection against herpes zoster infection and VHZ reactivation.

Vaccinations in pulmonary diseases - part 2: herpes zoste, RSV, pneumococcal infection and pertussis

RSV is a common cause of respiratory tract infections, posing a risk of severe disease, particularly for newborns and infants, as well as in older individuals with pre-existing conditions. Two safe and effective RSV vaccines were approved in 2023. These vaccines elicit protective antibodies and offer robust protection with no additional benefit from annual boosters. Both vaccines have been approved for individuals aged 60 years and older, while one of the vaccines has also been approved in pregnant women to elicit maternal immunity for passive protection of the unborn child. In Germany, RSV vaccination is currently recommended for all individuals aged 75 years and older, as well as people aged 60-74 years of age with severe underlying conditions. PNEUMOCOCCAL INFECTION: Streptococcus pneumoniae is a primary cause of community-acquired pneumonia (CAP). Since early 2022, a 20-valent conjugate vaccine (PCV20) is approved and recommended for people over 60 years of age and individuals over 18 years of age with risk factors. PCV20 replaces the 23-valent polysaccharide vaccine (PPV23) previously recommended for those over 60 years of age. Although viewed primarily as a childhood disease, the majority of infections affect adults. Patients with chronic respiratory diseases are at a higher risk for severe clinical course of pertussis infection. It has therefore been recommended that all adults should get a pertussis booster with their next scheduled tetanus vaccination, given as a combination vaccine (Tdap). For risk groups (healthcare personnel, community facilities) a booster vaccination every 10 years is recommended. Herpes Zoster (shingles) is caused by the varicella-zoster virus, and reactivations can lead to painful skin lesions and potential complications such as herpes zoster oticus, meningitis, or postherpetic neuralgia. People with chronic lung diseases such as COPD or asthma are at increased risk of herpes zoster-related complications. A recombinant adjuvanted inactivated vaccine was approved in 2018 and offers robust protection against herpes zoster and its complications. The vaccine is recommended for all people over 60 years of age and for certain risk groups over 50 years of age.

A Survey on Knowledge and Attitudes Towards Vaccination Against Herpes Zoster Virus Among Medical Oncologists for Patients with Solid Tumors.

Herpes zoster (HZ) virus reactivation is a significant medical problem among immunocompromised patients, especially considering its potential complications. Although the recombinant HZ vaccine has demonstrated > 90% efficacy against HZ in adults, its use is not as frequent as needed in daily oncology practice due to several barriers, including oncologists' knowledge, patients' willingness, and organizational issues. A web-based survey was sent to 139 oncologists treating solid tumors concerning their knowledge and attitudes toward the adjuvanted gE-based recombinant HZ vaccination. The survey included questions regarding the characteristics of medical oncologists participating, such as the type of hospital, main field of expertise, percent of work with patients, awareness of the HZ risk in cancer patients, knowledge of scientific data and scientific societies guidelines on HZ vaccination, familiarity with vaccinations, frequency of HZ detection in clinical practice, barriers, and challenges toward vaccine administration. Fifty-four physicians (46%; 95% CI 0.2918 to 0.5069) responded to all the questions. The main reason for non-response was the lack of time due to the overwhelming burden of assistance. When the survey was launched, 31 participants reported good knowledge of scientific and clinical data of HZ vaccines, 10% none, and 36 were aware of guidelines. Reported barriers included knowledge of the problem, patients' willingness, and organizational issues. Surveying medical oncologists on the adjuvanted gE-based recombinant HZ vaccination provides essential insights into their knowledge, attitudes, and practices regarding vaccination for cancer patients. These data suggest that continuing medical education is necessary to implement HZ vaccination prescription among oncologists.

Similar humoral responses but distinct CD4+ T cell transcriptomic profiles in older adults elicited by MF59 adjuvanted and high dose influenza vaccines.

Older age (≥ 65 years) is associated with impaired responses to influenza vaccination, leading to the preferential recommendation of MF59-adjuvanted (MF59Flu) or high-dose (HDFlu) influenza vaccines for this age group in the United States. Herein, we characterized transcriptomic profiles of CD4+ T cells isolated from 234 recipients (≥ 65 years) of either MF59Flu or HDFlu vaccine, prior to vaccination and 28 days thereafter. We identified 412 and 645 differentially expressed genes (DEGs) in CD4+ T cells of older adults after receiving MF59Flu and HDFlu, respectively. DEGs in CD4+ T cells of MF59Flu recipients were enriched in 14 KEGG pathways, all of which were downregulated. DEGs in CD4+ T cells of HDFlu recipients were enriched in 11 upregulated pathways and 20 downregulated pathways. CD4+ T cells in both vaccine groups shared 50 upregulated genes and 75 downregulated genes, all of which were enriched in 7 KEGG pathways. The remaining 287 and 520 DEGs were specifically associated with MF59Flu and HDFlu, respectively. Unexpectedly, none of these DEGs was significantly correlated with influenza A/H3N2-specific HAI titers, suggesting these DEGs at the individual level may have a limited role in protection against influenza. Our findings emphasize the need for further investigation into other factors influencing immunity against influenza in older adults.

Mixed Th1/Th2/Th17 Responses Induced by Plant Oil Adjuvant-Based B. bronchiseptica Vaccine in Mice, with Mechanisms Unraveled by RNA-Seq, 16S rRNA and Metabolomics.

The current Bordetella bronchiseptica (Bb) vaccine, when adjuvanted with alum, does not elicit adequate robust cellular immunity or effective antibody defense against Bb attacks. Unfortunately, antibiotic treatment generally represents an ineffective strategy due to the development of resistance against a broad range of antibiotics. The present study was designed to investigate the immune response, protective capabilities and underlying mechanisms of a plant oil-based adjuvant E515 formulated with inactivated Bb antigen as a potential vaccine candidate against Bordetella bronchiseptica. Immunization studies revealed that a combination of SO, VE and GS (E515) exhibited a good synergistic adjuvant effect. The E515 adjuvanted Bb vaccine was proven to be highly efficacious and induced a mixed Th1/Th2/Th17 immune response in mice, leading to a significant increase in Bb-specific IgG, IgG1 and IgG2a antibodies, proliferative lymphocyte responses and cytokine levels (by lymphocytes and serum) and effectively induced responses by CD4+ TE, TM cells and B cells. The E515 adjuvant significantly enhanced the immune protection provided by the Bb vaccine in a mice model, as indicated by a reduced bacterial burden in the lungs. Multi-omics sequencing analysis revealed that E515 functions as an adjuvant by modulating critical pathways, including cytokine-cytokine receptor interaction, the IL-17 signaling pathway and the chemokine signaling pathway. This modulation also included interactions with beneficial species of bacteria including Alistipes, Odoribacter and Colidextribacter, as well as energy and lipid-related metabolites, thus highlighting its role as an immunomodulatory agent. Collectively, our results demonstrate the huge potential of E515-Bb vaccine candidates, thus highlighting the vegetable oil original adjuvant E515 as a promising agent for the development of new veterinary vaccines.

Safety of Simultaneous Vaccination With Adjuvanted Zoster Vaccine and Adjuvanted Influenza Vaccine

Quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) and adjuvanted recombinant zoster vaccine (RZV) contain novel adjuvants. Data are limited on the comparative safety, reactogenicity, and health-related quality of life (HRQOL) effects of the simultaneous administration of these vaccines. To compare the safety and reactogenicity after simultaneous doses of RZV and aIIV4 administration (opposite arms) with simultaneous doses of RZV with quadrivalent high-dose inactivated influenza vaccine [HD-IIV4]). This randomized blinded clinical trial was conducted during the 2021-2022 and 2022-2023 influenza seasons at 2 centers in the US among community-dwelling adults aged 65 years or older. Analysis was performed on an intention-to-treat basis. Simultaneous intramuscular administration of RZV dose 1 and aIIV4 or HD-IIV4 in opposite arms after age stratification (65-69 and ≥70 years) and randomization. The primary outcome was the proportions of participants with 1 or more severe solicited reactions during days 1 to 8, using a noninferiority test (10% noninferiority margin). Additional measures included serious adverse events and adverse events of clinical interest during days 1 to 43 of the study period. A total of 267 adults (median age, 71 years [range, 65-92 years]; 137 men [51.3%]) were randomized; 130 received simultaneous RZV and aIIV4, and 137 received simultaneous RZV and HD-IIV4. The proportion of patients reporting 1 or more severe reactions after simultaneous administration of RZV and aIIV4 (15 of 115 [11.5%]) was noninferior compared with simultaneous RZV and HD-IIV4 (17 of 119 [12.5%]) (absolute difference, -1.0% [95% CI, -8.9% to 7.1%]). There were no significant differences in the number of serious adverse events or adverse events of clinical interest between the groups. In this clinical trial of simultaneous doses of RZV and aIIV4 compared with simultaneous doses of RZV and HD-IIV4, overall safety findings were similar between groups. From a safety standpoint, this study supports the simultaneous administration of RZV and aIIV4 among older adults. ClinicalTrials.gov Identifier: NCT05007041.

Systemic dysregulation and molecular insights into poor influenza vaccine response in the aging population.

Vaccination-induced protection against influenza is greatly diminished and increasingly heterogeneous with age. We investigated longitudinally (up to five time points) a cohort of 234 vaccinated >65-year-old vaccinees with adjuvanted vaccine FluAd across two independent seasons. System-level analyses of multiomics datasets measuring six modalities and serological data revealed that poor responders lacked time-dependent changes in response to vaccination as observed in responders, suggestive of systemic dysregulation in poor responders. Multiomics integration revealed key molecules and their likely role in vaccination response. High prevaccination plasma interleukin-15 (IL-15) concentrations negatively associated with antibody production, further supported by experimental validation in mice revealing an IL-15-driven natural killer cell axis explaining the suppressive role in vaccine-induced antibody production as observed in poor responders. We propose a subset of long-chain fatty acids as modulators of persistent inflammation in poor responders. Our findings provide a potential link between low-grade chronic inflammation and poor vaccination response and open avenues for possible pharmacological interventions to enhance vaccine responses.

Two-dose priming immunization amplifies humoral immunity by synchronizing vaccine delivery with the germinal center response.

Prolonging exposure to subunit vaccines during the primary immune response enhances humoral immunity. Escalating-dose immunization (EDI), administering vaccines every other day in an increasing pattern over 2 weeks, is particularly effective but challenging to implement clinically. Here, using an HIV Env trimer/saponin adjuvant vaccine, we explored simplified EDI regimens and found that a two-shot regimen administering 20% of the vaccine followed by the remaining 80% of the dose 7 days later increased TFH responses 6-fold, antigen-specific germinal center (GC) B cells 10-fold, and serum antibody titers 10-fold compared with bolus immunization. Computational modeling of TFH priming and the GC response suggested that enhanced activation/antigen loading on dendritic cells and increased capture of antigen delivered in the second dose by follicular dendritic cells contribute to these effects, predictions we verified experimentally. These results suggest that a two-shot priming approach can be used to substantially enhance responses to subunit vaccines.

Relative effectiveness of adjuvanted versus non-adjuvanted influenza vaccines in older adults with risk factors for influenza complications during the 2019–2020 U.S. influenza season

This study estimated the relative vaccine effectiveness (rVE) of the MF59®-adjuvanted trivalent influenza vaccine (aTIV) versus standard-dose nonadjuvanted egg-based quadrivalent influenza vaccines (QIVe) for the prevention of influenza-related medical encounters (IRMEs), outpatient IRMEs, and influenza- and pneumonia-related hospitalizations during the 2019–2020 US influenza season among adults ≥65 years of age who had ≥1 high-risk condition. A secondary objective evaluated the rVE of aTIV versus QIVe in preventing these outcomes among older adults with specific high-risk conditions. This retrospective cohort study included US adults ≥65 years of age vaccinated with aTIV or QIVe between August 1, 2019, and January 31, 2020. Exposures, covariates, risk factors, and outcomes were captured from a linked dataset comprised of electronic health records (EHR) (Veradigm Network EHR) linked to insurance claims (Komodo Healthcare Map). A doubly robust approach was applied wherein multivariable-adjusted odds ratios were derived using inverse probability of treatment-weighted samples to calculate rVEs and 95 % confidence interval independently for individuals ≥1 high-risk condition and those with specific high-risk conditions. The study included 954,707 aTIV and 719,125 QIVe recipients. For all outcomes, aTIV was more effective than QIVe among adults ≥65 years of age who had ≥1 high-risk condition (any IMRE: 23.6 % [20.9 %–26.1 %]), outpatient IRME: 23.3 % [20.4 %–26.1 %], and influenza- or pneumonia-related hospitalizations: 19.0 % [16.3 %–21.6 %]), during the 2019–2020 influenza season. Similarly, aTIV was more effective than QIVe at preventing outcomes among individuals with specific high-risk conditions except for body mass index ≥40. This study demonstrated higher effectiveness of aTIV versus QIVe in preventing any IRMEs, outpatient IRMEs, and influenza- or pneumonia-related hospitalizations among adults ≥65 years of age who had ≥1 high-risk condition.

Adjuvant Use of the Invariant-Natural-Killer-T-Cell Agonist α-Galactosylceramide Leads to Vaccine-Associated Enhanced Respiratory Disease in Influenza-Vaccinated Pigs.

Invariant natural killer T (iNKT) cells are glycolipid-reactive T cells with potent immunoregulatory properties. iNKT cells activated with the marine-sponge-derived glycolipid, α-galactosylceramide (αGC), provide a universal source of T-cell help that has shown considerable promise for a wide array of therapeutic applications. This includes harnessing iNKT-cell-mediated immune responses to adjuvant whole inactivated influenza virus (WIV) vaccines. An important concern with WIV vaccines is that under certain circumstances, they are capable of triggering vaccine-associated enhanced respiratory disease (VAERD). This immunopathological phenomenon can arise after immunization with an oil-in-water (OIW) adjuvanted WIV vaccine, followed by infection with a hemagglutinin and neuraminidase mismatched challenge virus. This elicits antibodies (Abs) that bind immunodominant epitopes in the HA2 region of the heterologous virus, which purportedly causes enhanced virus fusion activity to the host cell and increased infection. Here, we show that αGC can induce severe VAERD in pigs. However, instead of stimulating high concentrations of HA2 Abs, αGC elicits high concentrations of interferon (IFN)-γ-secreting cells both in the lungs and systemically. Additionally, we found that VAERD mediated by iNKT cells results in distinct cytokine profiles and altered adaptation of the challenge virus following infection compared to an OIW adjuvant. Overall, these results provide a cautionary note about considering the formulation of WIV vaccines with iNKT-cell agonists as a potential strategy to modulate antigen-specific immunity.

Inactivated LMBV vaccine with nano‑aluminum adjuvant provided immune protection in largemouth bass (Micropterus Salmoides)

Largemouth bass ranavirus (LMBV) has caused severe economic losses in largemouth bass (Micropterus salmoides) aquaculture. Vaccination is acknowledged as an efficient strategy to prevent viral diseases in fish. In this study, an inactivated virus vaccine with nano‑aluminum adjuvant was successfully developed to protect largemouth bass effectively against LMBV. LMBV was inactivated by formalin and mixed with nano‑aluminum adjuvant under moderate agitation. The nano‑aluminum hydroxide adjuvant showed a cuboidal structure under the scanning transmission electron microscope (STEM), scanning electron microscope (SEM), and transmission electron microscope (TEM), and LMBV antigen-adsorbing rate was 39.49 % superior to those of micro‑aluminum hydroxide and IMS1312 adjuvants. The results from both external and internal damage assessments indicated that the nano‑aluminum vaccine had good safety for Micropterus salmoides. The relative percentage of survival was 80 % with a booster immunization in largemouth bass. The expression levels of immune-related genes such as TNF-α, IFN, and IL-8 were significantly up-regulated in the spleen of fish immunized by nano‑aluminum adjuvant vaccine compared to those in inactivated LMBV and control groups. The neutralizing antibody in nano‑aluminum adjuvant vaccine group showed higher abundance and lasted for a longer period. Lymphocytes from the head kidney of largemouth bass in the nano‑aluminum adjuvant vaccine group showed stronger proliferation activity in vitro post-stimulation with ConA. Moreover, stronger migration of the dendritic cells was induced by the nano‑aluminum adjuvant vaccine. Collectively, our findings suggested that the inactivated LMBV vaccine with nano‑aluminum adjuvant could provide efficient protection for largemouth bass against LMBV infection. The nano‑aluminum adjuvant has potential application with inactivated viral vaccines in fish.

Protection against influenza hospitalizations from enhanced influenza vaccines among older adults: A systematic review and network meta-analysis.

Influenza vaccines are available to help protect persons aged ≥65 years, who experience thousands of influenza hospitalizations annually. Because some influenza vaccines may work better than others, we sought to assess benefit of high-dose (HD), adjuvanted (ADJ), and recombinant (RIV) influenza vaccines ("enhanced influenza vaccines") compared with standard-dose unadjuvanted influenza vaccines (SD) and with one another for prevention of influenza-associated hospitalizations among persons aged ≥65 years. We searched MEDLINE, Embase, CINAHL, Scopus, and Cochrane Library to identify randomized or observational studies published between January 1990 and October 2023 and reporting relative vaccine effectiveness (rVE) of HD, ADJ, or RIV for prevention of influenza-associated hospitalizations among adults aged ≥65 years. We extracted study data, assessed risk of bias, and conducted random-effects network meta-analysis and meta-regression. We identified 32 studies with 90 rVE estimates from five randomized and 27 observational studies (71,459,918 vaccinated participants). rVE estimates varied across studies and influenza seasons. Pooled rVE from randomized studies was 20% (95% CI -54 to 59) and 25% (95% CI -19 to 53) for ADJ and HD compared with SD, respectively; rVE was 6% (95% CI -109 to 58) for HD compared with ADJ; these differences were not statistically significant. In observational studies, ADJ, HD, and RIV conferred modestly increased protection compared with SD (rVE ranging from 10% to 19%), with no significant differences between HD, ADJ, and RIV. With enhanced vaccines combined, rVE versus SD was 18% (95% CI 3 to 32) from randomized and 11% (95% CI 8 to 14) from observational evidence. Meta-regression of observational studies suggested that those requiring laboratory confirmation of influenza reported greater benefit of enhanced vaccines. HD, ADJ, and RIV provided stronger protection than SD against influenza hospitalizations among older adults. No differences in benefit were observed in comparisons of enhanced influenza vaccines with one another.

2D Differential Metallic Immunopotentiators Drive High Diversity and Capability of Antigen-specific Immunity Against Tumor.

The therapeutic efficacy of vaccines for treating cancers in clinics remains limited. Here, a rationally designed cancer vaccine by placing immunogenically differential and clinically approved aluminum (Al)or manganese (Mn) in a 2D nanosheet (NS) architecture together with antigens is reported. Structurally optimal NS with a high molar ratio of Mn to Al (MANS-H) features distinctive immune modulation, markedly promoting the influx of heterogeneous innate immune cells at the injection site. Stimulation of multiple subsets of dendritic cells (DCs) significantly increases the levels, subtypes, and functionalities of antigen-specific T cells. MANS-H demonstrates even greater effectiveness in the production of antigen-specific antibodies than the commercial adjuvant (Alhydrogel) by priming T helper (Th)2 cells rather than T follicular helper (Tfh) cells. Beyond humoral immunity, MANS-H evokes high frequencies of antigen-specific Th1 and CD8+ cell immunity, which are comparable with Quil-A that is widely used in veterinary vaccines. Immunized mice with MANS-H adjuvanted vaccines exert strong potency in tumor regression by promoting effector T cells infiltrating at tumor and overcoming tumor resistance in multiple highly aggressive tumor models. The engineered immunogen with an intriguing NS architecture and safe immunopotentiators offers the next clinical advance in cancer immunotherapy.

Tumor lysate particle only vaccine (TLPO) vs. Tumor lysate particle-loaded, dendritic cell vaccine (TLPLDC) to prevent recurrence in resected stage III/IV melanoma patients: Results of a phase I/IIa trial

BackgroundThe autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is produced from dendritic cells (DC) loaded ex vivo with autologous tumor lysate (TL). TLPLDC has been shown to decrease recurrence in resected Stage III/IV melanoma patients in a Phase IIb trial. The TL particle only (TLPO) vaccine is produced by loading of yeast cell wall particles with autologous TL and direct injection allowing for in vivo DC loading. We have compared the TLPO and TLPLDC vaccines in an embedded Phase I/IIa trial of a larger Phase IIb trial of the TLPLDC vaccine. MethodsPatients rendered clinically disease-free after surgery were randomized 2:1 to receive the TLPO or TLPLDC vaccine and followed for recurrence and death. Patients had scheduled intradermal inoculations at 0, 1, 2, 6, 12, and 18 months after enrollment. Kaplan-Meier and log-rank analysis were used to compare disease-free survival (DFS) and overall survival (OS) in an intention-to-treat (ITT) analysis. ResultsSixty-three patients were randomized, 43 TLPO and 20 TLPLDC. Patients randomized to the TLPO arm were more likely to be female (37.2% vs. 10.0 %, p = 0.026), but otherwise no significant clinicopathological differences were identified. No differences in related adverse events (AE) were found between treatment arms. At a median follow-up of 20.5 months, the DFS (60.8% vs. 58.7 %, p = 0.714) and OS (94.6% vs. 93.8 %, p = 0.966) were equivalent between the TLPO and TLPLDC groups, respectively. No statistical differences were found in subgroup analyses between vaccine types, which accounted for receipt of immunotherapy and the use of G-CSF pre-blood draw. ConclusionsIn a randomized, double-blind Phase I/IIa trial, there were no differences in DFS or OS in resected Stage III/IV melanoma patients receiving adjuvant TLPO versus TLPLDC vaccines. Given manufacturing advantages, further efficacy testing of TLPO is warranted in a Phase III trial.

Production and Evaluation of an Inactivated Adjuvanted Vaccine against Canine Parvovirus in Morocco.

The study conducted in Morocco focused on addressing the challenges posed by canine parvovirus (CPV-2) through comprehensive research, vaccine development, and efficacy assessment. Through real-time PCR screening and genotyping, CPV-2 variants were identified circulating in the region. An inactivated vaccine, derived from a CPV-2 strain isolated from a symptomatic dog, was produced and evaluated for safety and efficacy. The vaccine, from the strain named "CaPV M/3-2022", demonstrated safety in vaccinated puppies, with no adverse reactions observed during the trial period. Efficacy trials showed that vaccinated puppies remained healthy and exhibited lower viral excretion post-challenge compared to unvaccinated controls. These results indicate that the vaccine effectively protects against illness related to CPV-2 and reduces viral shedding. The study provides valuable insights into CPV-2 epidemiology in Morocco, offers a promising vaccine solution, and underscores the importance of vaccination in controlling CPV-2 outbreaks and protecting canine health.