This study focuses on the development and characterization of an intranasal vaccine platform using adjuvanted nanoparticulate delivery of swine influenza A virus (SwIAV). The vaccine employed whole inactivated H1N2 SwIAV as an antigen and STING-agonist ADU-S100 as an adjuvant, with both surface adsorbed or encapsulated in mannose-chitosan nanoparticles (mChit-NPs). Optimization of mChit-NPs included evaluating size, zeta potential, and cytotoxicity, with a 1:9 mass ratio of antigen to NP demonstrating high loading efficacy and non-cytotoxic properties suitable for intranasal vaccination. In a heterologous H1N1 pig challenge trial, the mChit-NP intranasal vaccine induced cross-reactive sIgA antibodies in the respiratory tract, surpassing those of a commercial SwIAV vaccine. The encapsulated mChit-NP vaccine induced high virus-specific neutralizing antibody and robust cellular immune responses, while the adsorbed vaccine elicited specific high IgG and hemagglutinin inhibition antibodies. Importantly, both the mChit-NP vaccines reduced challenge heterologous viral replication in the nasal cavity higher than commercial swine influenza vaccine. In summary, a novel intranasal mChit-NP vaccine platform activated both the arms of the immune system and is a significant advancement in swine influenza vaccine design, demonstrating its potential effectiveness for pig immunization.

BACKGROUND: In France, influenza accounts for an average of over one million consultations with GPs, 20,000 hospitalizations, and 9000 deaths per year, particularly among the over-65s. This study evaluates the cost-effectiveness of the adjuvanted quadrivalent influenza vaccine (aQIV) compared to standard (SD-QIV) and high-dose (HD-QIV) quadrivalent influenza vaccines for individuals aged 65 and older in France.
METHODS: The age-structured SEIR transmission model, calibrated to simulate a mean influenza season, incorporates a contact matrix to estimate intergroup contact rates. Epidemiological, economic, and utility outcomes are evaluated. Vaccine effectiveness and costs are derived from literature and national insurance data. Quality of life adjustments for influenza attack rates and hospitalizations are applied. Deterministic and probabilistic analyses are also conducted.
RESULTS: Compared to SD-QIV, aQIV demonstrates substantial reductions in healthcare utilization and mortality, avoiding 89,485 GP consultations, 2144 hospitalizations, and preventing 1611 deaths. Despite an investment of EUR 110 million, aQIV yields a net saving of EUR 14 million in healthcare spending. Compared to HD-QIV, aQIV saves 62 million euros on vaccination costs. Cost-effectiveness analysis reveals an incremental cost-effectiveness ratio of EUR 7062 per QALY.
CONCLUSIONS: This study highlights the cost-effectiveness of aQIV versus SD-QIV and HD-QIV, preventing influenza cases, hospitalizations, and deaths.

Streptococcosis, an emerging infectious disease caused by Streptococcus agalactiae, has had adverse effects on farmed tilapia. Several vaccines have been developed to prevent this disease and induce a specific immune response against S. agalactiae infection. In this study the use of MONTANIDE™ GR01, a new adjuvant for oral vaccination, was optimized for use in tilapia under laboratory and field studies. In the laboratory trial the immune response and protective efficacy of two doses of MONTANIDE™ GR01, 20 % (w/w) and 2 % (w/w), included into the feed-based adjuvanted vaccines were assessed comparatively. Following immunization, the innate immune parameters studied in serum, including lysozyme, myeloperoxidase, catalase and glutathione peroxidase activity, were all increased significantly. Furthermore, specific IgM antibodies against S. agalactiae were induced significantly in serum post-vaccination, with higher levels observed in both groups that received the feed-based adjuvanted vaccine. Under both injection and immersion challenge conditions, the relative percent survival for the feed-based adjuvanted vaccine groups ranged from 78 % to 84 %. Following use of the low dose concentration of MONTANIDE™ GR01 for oral vaccination of tilapia in cage culture systems, several innate immune parameters were effectively enhanced in the immunized fish. Similarly, the levels of specific IgM antibodies in the serum of feed-based vaccinated fish were significantly enhanced, reaching their highest levels 2-5 months post-vaccination. Cytokines associated with innate and adaptive immunity were also examined, and the expression levels of several genes showed significant up-regulation. This indicates that both cellular and humoral immune responses were induced by the feed-based adjuvanted vaccine. The economic impact of a feed-based adjuvanted vaccine was examined following vaccination, considering the growth performance and feed utilization of the fish. It was found that the Economic Performance Index and Economic Conversion Ratio were unaffected by vaccination, further demonstrating that there are no negative impacts associated with administering a feed-based vaccine to fish. In conclusion, the data from this study indicate that MONTANIDE™ GR01 is a highly valuable adjuvant for oral vaccination, as demonstrated by its ability to induce a strong immune response and effectively prevent streptococcal disease in Nile tilapia.

BACKGROUND: Chronic hepatitis B (HB) remains a significant global health concern, despite the widespread availability of the HB vaccine. While the standard vaccine demonstrates an impressive serological response rate exceeding 90%, a subset of individuals exhibit suboptimal immunity. This study aims to elucidate the efficacy of the AS04C-adjuvanted HB vaccine in addressing non-responsiveness.
METHODS: Conducted at the Preventive Medicine Service of the University Albacete Hospital in Spain from 2017 to 2021, this single-center observational study enrolled 195 patients. Among them, 126 (65%) were classified as non-responders following one or two complete standard vaccination courses.
RESULTS: After the administration of a complete four-dose regimen of the AS04C-adjuvanted vaccine, 73.81% of non-responder patients exhibited antibody titers indicative of robust immunity (anti-HBs >10).
CONCLUSIONS: These findings underscore the pivotal role of the AS04C-adjuvanted HB vaccine in addressing non-responsiveness, emphasizing its potential as a crucial tool in augmenting immunization strategies for various populations. This includes non-responders to standard vaccination, individuals with chronic kidney disease, those requiring seroprotection due to factors like immunosuppression or occupational hazards, as well as patients for whom conventional revaccination strategies have proven futile. Additional research is needed to expand on the promising results obtained through our protocol.

COVID-19 continues to cause an increase in the number of cases and deaths worldwide. Due to the ever-mutating nature of the virus, frequent vaccination against COVID-19 is anticipated. Most of the approved SARS-CoV-2 vaccines are administered using the conventional intramuscular route, causing vaccine hesitancy. Thus, there is a need for an effective, non-invasive vaccination strategy against COVID-19. This study evaluated the synergistic effects of a subunit microparticulate vaccine delivered using microneedles. The microparticles encapsulated a highly immunogenic subunit protein of the SARS-CoV-2 virus, such as the spike protein\'s receptor binding domain (RBD). Adjuvants were also incorporated to enhance the spike RBD-specific immune response. Our vaccination study reveals that a microneedle-based vaccine delivering these microparticles induced spike RBD-specific IgM, IgG, IgG1, IgG2a, and IgA antibodies. The vaccine also generated high levels of CD4+ and CD8a+ molecules in the secondary lymphoid organs. Overall, dissolving microneedles delivery spike RBD antigen in microparticulate form induced a robust immune response, paving the way for an alternative self-administrable, non-invasive vaccination strategy against COVID-19.

Most of the complications and deaths related to seasonal flu occur in the elderly population (≥65 years) with comorbidities, and the influenza vaccine is the most effective way to prevent them. Immunization is less effective in older adults due to immunosenescence. MF59-adjuvanted vaccines, designed to improve the magnitude, persistence and amplitude of the immune response in elderly people, have been used in clinical practice since 1997 in their trivalent formulation and, since 2020, in their tetravalent formulation. Data from various studies show that these vaccines are not only safe for all age groups, with a reactogenicity profile similar to that of the conventional vaccine, but also that they are especially effective in boosting the immune response in the population aged 65 or over by increasing antibody titers after vaccination and significantly reducing the risk of hospital admission. Adjuvanted vaccines have been shown to provide cross-protection against heterologous strains and to be as effective as the high-dose vaccine in the population aged 65 or over. In this review, the scientific evidence on the efficacy and effectiveness of the MF59-adjuvanted vaccine in real clinical practice in people ≥65 years of age is analyzed through a narrative and descriptive review of the literature with data from clinical trials, observational studies and systematic reviews or meta-analysis.

The outer-membrane-derived proteoliposome (PL) of Neisseria meningitidis has been reported as a potent vaccine adjuvant, inducing a Th1-skewed response. This work aimed to assess the immunogenicity of a novel anti-allergic vaccine candidate based on allergens from Dermatophagoides siboney house dust mite and a combination adjuvant containing PL and Alum. In a preventative experimental setting, BALB/c mice were administered with three doses containing 2 µg of Der s1 and 0.4 µg Der s2 allergen, PL and Alum, at 7 days intervals, by subcutaneous route. Furthermore, mice were subjected to an allergen aerosol challenge for 6 consecutive days. Serum IgE, IgG1, and IgG2a allergen-specific antibodies were assessed by ELISA. Cytokine levels in supernatants of D. siboney stimulated lymphocyte cultures and in bronchoalveolar lavage (BAL) were measured by ELISA. Lung tissues were subjected to histological examination. The vaccine prevented the development of both, systemic (IgE) and local allergic responses (featuring lower IL-4, and IL-5 levels in BAL) upon allergen exposure by the inhalant route. Histological examination showed also a diminished allergic inflammatory response in the lungs. After the allergen challenge, cytokine levels in stimulated lymphocyte cultures showed lower values of IL-13 and augmented IFN-γ and IL-10. The vaccine induced a mixed IgG2a/IgG1 antibody response; although only IgG2a was PL-dependent. Both, IgG1/IgE and IgG2a/IgE ratios, showed significantly greater values in vaccinated mice. The findings support a preventative anti-allergic effect associated with the induction of a Th1-like IFN-γ/IL-10 response. IgG1/IgE and IgG2a/IgE ratios could be useful biomarkers for translation into clinical trials.

We aimed to evaluate the safety and optimal dose of a novel inactivated whole-virus adjuvanted vaccine against SARS-CoV-2: VLA2001.
We conducted an open-label, dose-escalation study followed by a double-blind randomized trial using low, medium and high doses of VLA2001 (1:1:1). The primary safety outcome was the frequency and severity of solicited local and systemic reactions within 7 days after vaccination. The primary immunogenicity outcome was the geometric mean titre (GMT) of neutralizing antibodies against SARS-CoV-2 two weeks after the second vaccination. The study is registered as NCT04671017.
Between December 16, 2020, and June 3, 2021, 153 healthy adults aged 18-55 years were recruited in the UK. Overall, 81.7% of the participants reported a solicited AE, with injection site tenderness (58.2%) and headache (46.4%) being the most frequent. Only 2 participants reported a severe solicited event. Up to day 106, 131 (85.6%) participants had reported any AE. All observed incidents were transient and non-life threatening in nature. Immunogenicity measured at 2 weeks after completion of the two-dose priming schedule, showed significantly higher GMTs of SARS-CoV-2 neutralizing antibody titres in the highest dose group (GMT 545.6; 95% CI: 428.1, 695.4) which were similar to a panel of convalescent sera (GMT 526.9; 95% CI: 336.5, 825.1). Seroconversion rates of neutralizing antibodies were also significantly higher in the high-dose group (>90%) compared to the other dose groups. In the high dose group, antigen-specific IFN-γ expressing T-cells reactive against the S, M and N proteins were observed in 76, 36 and 49%, respectively.
VLA2001 was well tolerated in all tested dose groups, and no safety signal of concern was identified. The highest dose group showed statistically significantly stronger immunogenicity with similar tolerability and safety, and was selected for phase 3 clinical development.

2018/19 was the first season of introduction in England of a newly licensed adjuvanted influenza vaccine (aTIV) for adults 65 years or older, who were previously offered standard-dose, non-adjuvanted vaccine, achieving uptake levels >70%, often with poor effectiveness. This paper presents the end-of-season adjusted vaccine effectiveness (aVE) against laboratory confirmed influenza hospitalisation in this population. A frequency-matched test negative case control approach was used to estimate aVE by influenza A subtype and vaccine type. Cases were influenza confirmed hospitalisations and controls influenza negative hospitalisations who were 65 years or more. Cases and controls were selected from a sentinel laboratory surveillance system which collates details of inpatients and outpatients routinely tested on clinical advice for influenza infection with reverse-transcription polymerase chain reaction (RT-PCR) on respiratory samples. Vaccine and clinical history was obtained from the general practitioners of study participants. A total of 428 cases and 1013 controls were included in the analysis. End-of-season any-influenza aVE against hospitalisation was 53.4% (95% CI: 39.9, 63.9). By influenza A subtype, aVE was 64.8% (95% CI: 49.6, 75.3) against influenza A(H1N1)pdm09 and 39.3% (95% CI: 6.5, 60.6) against influenza A(H3N2). There was insufficient data to estimate influenza B VE. aVE estimates for all influenza, influenza A(H1N1)pdm09 and influenza A(H3N2) for aTIV were 53.8% (39.8, 64.5); 65.9% (50.6, 76.4) and 39.5% (4.8, 61.5) respectively. We provide evidence of significant influenza VE in the elderly, most notably against influenza A(H1N1)pdm09, but also against A(H3N2) for aTIV.

Herpes Zoster (HZ) presents a considerable public health burden in Italy among people aged ≥50 years. This study aimed to assess the clinical and economic impact of HZ vaccination in the 65 years of age (YOA) cohort in Italy, by comparing the new Adjuvanted Recombinant Zoster Vaccine (RZV) with the currently available Zoster Vaccine Live (ZVL). A static Markov model was developed to follow all 65 YOA subjects from the year of vaccination over their lifetime by comparing three different HZ vaccination strategies: no vaccination, vaccination with ZVL and vaccination with RZV. In the base-case scenario, three 65 YOA cohorts were assumed to be vaccinated within three years, with a vaccine coverage rate of 20%, 35% and 50% at Year 1, 2 and 3 respectively, as recommended by the National Immunization Plan. The three 65 YOA Italian cohorts accounted altogether for 2,290,340 individuals. Of these, it was assumed that 564,178 subjects could be vaccinated with either RZV or ZVL in three years. The vaccination with RZV could prevent an additional total number of 35,834 HZ and 8,131 postherpetic neuralgia (PHN) cases over ZVL, leading to additional total savings of €12.4 million for the national healthcare and social systems. The introduction of RZV can be expected to have higher impact on the burden of HZ disease in the 65 YOA cohort in Italy. The avoided HZ and PHN cases can lead to an associated reduction in economic burden to the healthcare and social systems.