Search Results (94)

Background: Fowl typhoid (FT), a septicemic infection caused by Salmonella Gallinarum (SG), and H9N2 avian influenza are two economically important diseases that significantly affect the global poultry industry. Methods: We exploited the live attenuated Salmonella Gallinarum (SG) mutant JOL3062 (SG: ∆lon ∆pagL ∆asd) as a delivery system for H9N2 antigens to induce an immunoprotective response against both H9N2 and FT. To enhance immune protection against H9N2, a prokaryotic and eukaryotic dual expression plasmid, pJHL270, was employed. The hemagglutinin (HA) consensus sequence from South Korean avian influenza A virus (AIV) was cloned under the Ptrc promoter for prokaryotic expression, and the B cell epitope of neuraminidase (NA) linked with matrix protein 2 (M2e) was placed for eukaryotic expression. In vitro and in vivo expressions of the H9N2 antigens were validated by qRT-PCR and Western blot, respectively. Results: Oral immunization with JOL3121 induced a significant increase in SG and H9N2-specific serum IgY and cloacal swab IgA antibodies, confirming humoral and mucosal immune responses. Furthermore, FACS analysis showed increased CD4+ and CD8+ T cell populations. On day 28 post-immunization, there was a substantial rise in the hemagglutination inhibition titer in the immunized birds, demonstrating neutralization capabilities of immunization. Both IFN-γ and IL-4 demonstrated a significant increase, indicating a balance of Th1 and Th2 responses. Intranasal challenge with the H9N2 Y280 strain resulted in minimal to no clinical signs with significantly lower lung viral titer in the JOL3121 group. Upon SG wildtype challenge, the immunized birds in the JOL3121 group yielded 20% mortality, while 80% mortality was recorded in the PBS control group. Additionally, bacterial load in the spleen and liver was significantly lower in the immunized birds. Conclusions: The current vaccine model, designed with a host-specific pathogen, SG, delivers a robust immune boost that could enhance dual protection against FT and H9N2 infection, both being significant diseases in poultry, as well as ensure public health. Full article

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its impact on public health continue to demand attention as the virus continues to evolve, demonstrating a remarkable ability to adapt to diverse selective pressures including immune responses, therapeutic treatments, and prophylactic interventions. The SARS-CoV-2 variant landscape remains dynamic, with new subvariants continuously emerging, many harboring spike protein mutations linked to immune evasion. In this study, we characterized a panel of live SARS-CoV-2 strains, including those key subvariants implicated in recent waves of infection. Our findings revealed a significant variability in mutation patterns in the spike protein across the strains analyzed. Commercial antibodies and human convalescent plasma (HCoP) samples from unvaccinated donors were ineffective in neutralizing the most recent Omicron subvariants, particularly after the emergence of JN.1 subvariant. Using human airway epithelial cells derived from healthy bronchiolar tissue (hBAEC), we established both monoinfections and coinfections involving SARS-CoV-2, Influenza A virus H1N1 (IFAV_H1N1) and Respiratory Syncytial Virus (RSV). Assessments were conducted to compare viral infectivity and the production and release of immune mediators in the apical and basolateral compartments. Notably, Omicron KP.3.1.1 subvariant induced a more pronounced cytopathic effect in hBAEC compared to its parental strain JN.1 and even surpassed the impact observed with the ancestral wild-type virus (WA1/2020, Washington strain). Furthermore, the coinfection of KP.3.1.1 subvariant with IFAV_H1N1 or RSV did not attenuate SARS-CoV-2 infectivity; instead, it significantly exacerbated the pathogenic synergy in the lung epithelium. Our study demonstrated that pro-inflammatory cytokines IL-6, IFN-β, and IL-10 were upregulated in hBAEC following SARS-CoV-2 monoinfection with recent Omicron subvariants as well as during coinfection with IFAV_H1N1 and RSV. Taken together, our findings offer new insights into the immune evasion strategies and pathogenic potential of evolving SARS-CoV-2 Omicron subvariants, as well as their interactions with other respiratory viruses, carrying important implications for therapeutic development and public health preparedness. Full article

Introduction: Herpes zoster (HZ), or shingles, is a vaccine-preventable disease with two approved vaccines: the live-attenuated vaccine (LZV) and the adjuvanted recombinant zoster vaccine (RZV). Evidence on the immunogenicity and adverse events (AEs) following co-administration with other vaccines in adults is limited. This systematic review and meta-analysis aims to evaluate the immunogenicity and safety of HZ vaccines when co-administered with other vaccines. Methods: We followed PRISMA 2020 guidelines and systematically searched multiple databases (January 1950 to February 2024) for studies on HZ vaccination with concomitant vaccines in adults (≥18 years). Observational studies, randomized controlled trials (RCTs), and non-randomized controlled trials were included, excluding reviews, case series, case reports, editorials, and non-English publications. Risk of bias was assessed using Cochrane tools (RoB 2 and ROBINS-I). A meta-analysis compared geometric mean concentration (GMC) ratios and vaccine response rates (VRRs) for RZV, applying the Hartung–Knapp adjustment. For LZV, meta-analysis was not feasible, and results were described narratively. AEs were analyzed using risk ratios and presented in forest plots. Results: Out of 369 search hits, ten RCTs were included. In six RCTs, RZV was co-administered with influenza, COVID-19, pneumococcal vaccines (PCV13, PPSV23), or Tdap. The pooled GMC mean difference was −0.04 (95% CI: −0.10 to 0.02, p = 0.19), and the pooled VRR was 1.00 (95% CI: 0.99 to 1.01, p = 0.59). Local and systemic AEs showed pooled relative risks of 0.99 (95% CI: 0.95 to 1.03, p = 0.73) and 1.01 (95% CI: 0.91 to 1.11, p = 0.90), respectively. LZV co-administration was investigated in four RCTs and was safe; however, co-administration with PPSV23 resulted in reduced immunogenicity. Conclusions: The co-administration of RZV with other vaccines was safe and immunogenic. However, limited evidence suggests that co-administration of LZV with PPSV23 reduced the immunogenicity of LZV through an unknown mechanism. Still, RZV co-administration could enhance vaccine uptake in vulnerable populations. Full article

Background/Objectives: Eurasian avian-like (EA) H1N1 swine influenza viruses, with their persistent evolution and zoonotic potential, seriously threaten both swine and human health. The objective was to develop an effective vaccine against these viruses. Methods: A cold-adapted, temperature-sensitive live-attenuated influenza vaccine (LAIV) candidate, GX18ca, was developed. It was derived from the wild-type EA H1N1 strain A/swine/Guangxi/18/2011 (GX18) through serial passaging in embryonated eggs at temperatures decreasing from 33 °C to 25 °C. Its characteristics were studied in mice, including attenuation, immune responses (mucosal IgA, serum IgG, IFN-γ+ CD4⁺/CD8⁺ T-cell responses), and protective efficacy against homologous (GX18), heterologous EA H1N1 (LN972), and human 2009/H1N1 (SC1) viruses. Results: GX18ca showed cold-adapted and temperature-sensitive phenotypes. In mice, it was attenuated, with viral titers in the nasal turbinates and lungs reduced 1000–10,000-fold compared to the wild-type strain, and it cleared by day 5 post infection. Intranasal immunization elicited strong cross-reactive immune responses. Mucosal IgA had broad reactivity, and serum IgG titers reached high levels. IFN-γ+ CD4^+/CD8⁺ T-cell responses were detected against all the tested viruses. A single dose of GX18ca fully protected against GX18 and LN972 challenges, and two doses significantly reduced SC1 lung viral loads, preventing mortality and weight loss. Conclusions: GX18ca is a promising LAIV candidate. It can induce broad immunity, addressing the cross-protection gaps against evolving EA H1N1 SIVs and zoonotic H1N1 variants, which is crucial for swine influenza control and pandemic preparedness. Full article

Children with hemato-oncological diseases represent a heterogeneous population at heightened risk for vaccine-preventable diseases. Their immunosuppressed state reduces vaccine efficacy and raises safety concerns regarding live attenuated vaccines due to the risk of viral reactivation. The immunological and clinical implications of the single conditions are significantly different; therefore, specific vaccination strategies are needed. Despite the availability of vaccine guidelines for immunocompromised patients, clinical practice remains highly variable. It is generally recommended to avoid vaccinations during chemotherapy, with some exceptions for influenza, pneumococcal, and, in some countries, hepatitis B vaccines. The timing of immune recovery after chemotherapy depends on the specific treatment and most guidelines recommend administering vaccines 3–6 months after treatment cessation. Concerning HSCT, the timing of immune recovery is affected by several factors such as the HSCT platform, graft-versus-host disease (GvHD), and infections. Inactivated vaccines are typically administered 3–6 months post-HSCT, while live attenuated vaccines are delayed for at least two years. In children with asplenia or hyposplenism, recommendations focus on immunization against encapsulated bacteria, with tailored schedules based on the patient’s age and underlying condition. This paper explores the biological factors influencing vaccination efficacy and safety in pediatric hematology and oncology patients. It also provides an updated overview of the available evidence and current vaccination guidelines. Finally, this paper highlights the main clinical and research areas for further improvement to provide tailored vaccination schedules for this vulnerable population. Full article

Influenza vaccination is the health intervention that best guarantees protection against seasonal influenza. Every year, the Ministry of Health issues a document (namely a circular) containing recommendations for the use of available vaccines to prevent and control influenza. A review of the Ministerial Circulars released by the Italian Ministry of Health was conducted with the aim of assessing the evolution over time of the vaccination target recipients, the vaccines that can be used in the following influenza season, and the indications of use for age and appropriateness. Changes have emerged regarding these issues. In fact, over time, the vaccination offer has been extended to children between 6 months and 6 years of age, to adults aged 60–64 years, and to women in any trimester of pregnancy and postpartum. In parallel, from the 2018–2019 season, following the availability of new vaccines, the concept of vaccine appropriateness was introduced to the recommendations, i.e., the choice of the most appropriate vaccine for each subject to be vaccinated. The last circulars introduced the indication of the type of vaccine that can be administered for each target category and the recommendation to use adjuvanted and high-dose vaccines for adults aged ≥ 65 years. The annual recommendations provided by the Italian Ministry of Health, resultantly, are increasingly precise, emphasizing the importance of the concept of appropriateness and outlining the path to precision vaccination. To achieve maximum value in terms of clinical efficacy and community benefits, this concept should continue to be considered as a basis for the development of future recommendations, as it addresses a critical public health issue related to vaccination. Full article

Objective: This study systematically reviews health economic evaluations of influenza vaccines in China and synthesizes the evidence on different vaccine categories. Methods: We searched databases, including the China Hospital Knowledge Database, Wanfang, PubMed, Web of Science, and Embase, for studies on the health economics of influenza vaccines in China from 2015 to 2024. Studies were selected based on predefined criteria, and relevant data were extracted for analysis. The research utilized a parameter, ICER/threshold, defined as the ICER divided by the GDP per capita, to compare the results of cost-effectiveness analysis (CEA) studies. Results: A total of 1743 articles were identified, of which 25 met the inclusion criteria for full-text review. These included 19 Chinese studies and 6 English studies. Study populations were predominantly older adults (52.0%), followed by children, adolescents, people with chronic disease, and pregnant women. Vaccination strategies included trivalent inactivated influenza vaccine (TIV), quadrivalent inactivated influenza vaccine (QIV), trivalent live-attenuated influenza vaccine (LAIV), and non-vaccination groups. For TIV, 94.7% reported positive cost-effectiveness or cost-benefit results, with 21.1% identifying it as the most dominant strategy. For QIV, six studies compared it with a non-vaccinated group, and five (83.3%) reported favorable economic results. The study on LAIV showed cost-effectiveness compared to no vaccination, but not compared to QIV. The ICER threshold for TIV is the most favorable, and the population that exhibits the highest cost-effectiveness and benefit from vaccination is those people with underlying health conditions. Conclusions: TIV vaccination is often cost-effective, especially for people with chronic diseases, children, and older adults. Prioritizing TIV vaccination for those people with chronic diseases is recommended. Full article

Human immunodeficiency virus (HIV)-infected individuals have an increased risk of various infections due to their impaired host immune system, resulting in higher morbidity and mortality rates. These patients severely suffered during the COVID-19 epidemic, the influenza epidemic and the spread of monkeypox. Reducing serious infections is one of the most important measures to improve HIV-infected individuals’ quality and length of life. Based on the preparation processes and their antigenic properties, vaccines are divided into several types, including inactivated vaccines, attenuated live vaccines, recombinant protein vaccines, toxoid vaccines, polysaccharide vaccines, polysaccharide (protein) combined vaccines, nucleic acid vaccines, viral vector vaccines, etc. With the innovation of vaccine preparation technology in recent years and the acceleration of vaccine approval and market launch, more and more vaccine products suitable for HIV-infected individuals have become available. Because of their deficient immune systems, the type of vaccines and the schedule of vaccinations available to individuals living with HIV are sometimes different from those with healthy immune systems. This article reviewed the current status of vaccination in and shed light on the vaccination strategies for HIV-infected persons in terms of their safety and effectiveness. Full article

Background/Objectives: Haematopoietic stem cell transplantation (HCT) induces profound immunosuppression, significantly increasing susceptibility to severe infections. This review examines vaccinations’ necessity, timing, and efficacy post-HCT to reduce infection-related morbidity and mortality. It aims to provide a structured protocol aligned with international and national recommendations. Methods: A systematic review of current guidelines and studies was conducted to assess vaccination strategies in HCT recipients. The analysis included the timing of vaccine administration, factors influencing efficacy, and contraindications. Recommendations for pre- and post-transplant vaccination schedules were synthesised, specifically for graft-versus-host disease (GVHD), immunosuppressive therapy, and hypogammaglobulinemia. Results: Vaccination is essential as specific immunity is often lost after HCT. Inactivated vaccines are recommended to commence three months post-transplant, including influenza, COVID-19, and pneumococcal vaccines. Live attenuated vaccines remain contraindicated for at least two years post-transplant and in patients with ongoing GVHD or immunosuppressive therapy. Factors such as GVHD and immunosuppressive treatments significantly impact vaccine timing and efficacy. The review also underscores the importance of pre-transplant vaccinations and ensuring that patients’ close contacts are adequately immunised to reduce transmission risks. Conclusions: Implementing a structured vaccination protocol post-HCT is critical to improving patient outcomes. Timely and effective vaccination strategies can mitigate infection risks while addressing individual patient factors such as GVHD and immunosuppression. This review highlights the need for tailored vaccination approaches to optimize immune reconstitution in HCT recipients. Full article

Background: Acute otitis media (AOM) is a common pediatric infection worldwide and is the primary basis for pediatric primary care visits and antibiotic prescriptions in children. Current licensed vaccines have been incompletely ineffective at reducing the global burden of AOM, underscoring a major unmet medical need. The complex etiology of AOM presents additional challenges for vaccine development, as it can stem from multiple bacterial species including Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. As such, targeting multiple pathogens simultaneously may be required to significantly impact the overall disease burden. Methods: In this study, we aim to overcome this challenge by engineering a live-attenuated vaccine platform based on an attenuated mutant of S. pneumoniae that expresses H. influenzae and M. catarrhalis surface epitopes to induce protective immunity against all three pathogens. Results: The trivalent live-attenuated vaccine conferred significant protection against all three bacterial otopathogens as measured by seroconversion and the development of AOM, with the inclusion of the additional epitopes providing unexpected synergy and enhanced protection against S. pneumoniae. Conclusions: These data demonstrate a novel mechanism of introducing non-native immunogenic antigens into a live-attenuated vaccine platform to engender protection against AOM from multiple pathogenic species. Full article

The development of vaccines against RNA viruses has undergone a rapid evolution in recent years, particularly driven by the COVID-19 pandemic. This review examines the key roles that RNA viruses, with their high mutation rates and zoonotic potential, play in fostering vaccine innovation. We also discuss both traditional and modern vaccine platforms and the impact of new technologies, such as artificial intelligence, on optimizing immunization strategies. This review evaluates various vaccine platforms, ranging from traditional approaches (inactivated and live-attenuated vaccines) to modern technologies (subunit vaccines, viral and bacterial vectors, nucleic acid vaccines such as mRNA and DNA, and phage-like particle vaccines). To illustrate these platforms’ practical applications, we present case studies of vaccines developed for RNA viruses such as SARS-CoV-2, influenza, Zika, and dengue. Additionally, we assess the role of artificial intelligence in predicting viral mutations and enhancing vaccine design. The case studies underscore the successful application of RNA-based vaccines, particularly in the fight against COVID-19, which has saved millions of lives. Current clinical trials for influenza, Zika, and dengue vaccines continue to show promise, highlighting the growing efficacy and adaptability of these platforms. Furthermore, artificial intelligence is driving improvements in vaccine candidate optimization and providing predictive models for viral evolution, enhancing our ability to respond to future outbreaks. Advances in vaccine technology, such as the success of mRNA vaccines against SARS-CoV-2, highlight the potential of nucleic acid platforms in combating RNA viruses. Ongoing trials for influenza, Zika, and dengue demonstrate platform adaptability, while artificial intelligence enhances vaccine design by predicting viral mutations. Integrating these innovations with the One Health approach, which unites human, animal, and environmental health, is essential for strengthening global preparedness against future RNA virus threats. Full article

Background/Objectives: Influenza viruses and SARS-CoV-2 are currently cocirculating with similar seasonality, and both pathogens are characterized by a high mutational rate which results in reduced vaccine effectiveness and thus requires regular updating of vaccine compositions. Vaccine formulations combining seasonal influenza and SARS-CoV-2 strains can be considered promising and cost-effective tools for protection against both infections. Methods: We used a licensed seasonal trivalent live attenuated influenza vaccine (3×LAIV) as a basis for the development of a modified 3×LAIV/CoV-2 vaccine, where H1N1 and H3N2 LAIV strains encoded an immunogenic cassette enriched with conserved T-cell epitopes of SARS-CoV-2, whereas a B/Victoria lineage LAIV strain was unmodified. The trivalent LAIV/CoV-2 composition was compared to the classical 3×LAIV in the golden Syrian hamster model. Animals were intranasally immunized with the mixtures of the vaccine viruses, twice, with a 3-week interval. Immunogenicity was assessed on day 42 of the study, and the protective effect was established by infecting vaccinated hamsters with either influenza H1N1, H3N2 or B viruses or with SARS-CoV-2 strains of the Wuhan, Delta and Omicron lineages. Results: Both the classical 3×LAIV and 3×LAIV/CoV-2 vaccine compositions induced similar levels of serum antibodies specific to all three influenza strains, which resulted in comparable levels of protection against challenge from either influenza strain. Protection against SARS-CoV-2 challenge was more pronounced in the 3×LAIV/CoV-2-immunized hamsters compared to the classical 3×LAIV group. These data were accompanied by the higher magnitude of virus-specific cellular responses detected by ELISPOT in the modified trivalent LAIV group. Conclusions: The modified trivalent live attenuated influenza vaccine encoding the T-cell epitopes of SARS-CoV-2 can be considered a promising tool for combined protection against seasonal influenza and COVID-19. Full article

Between 2013 and 2016, the A/H1N1pdm09 component of the live attenuated influenza vaccine (LAIV) produced instances of lower-than-expected vaccine effectiveness. Standard pre-clinical ferret models, using a human-like vaccine dose and focusing on antigenic match to circulating wildtype (wt) strains, were unable to predict these fluctuations. By optimising the vaccine dose and utilising clinically relevant endpoints, we aimed to develop a ferret efficacy model able to reproduce clinical observations. Ferrets were intranasally vaccinated with 4 Log₁₀ FFU/animal (1000-fold reduction compared to clinical dose) of seven historical LAIV formulations with known (19–90%) H1N1 vaccine efficacy or effectiveness (VE). Following homologous H1N1 wt virus challenge, protection was assessed based on primary endpoints of wt virus shedding in the upper respiratory tract and the development of fever. LAIV formulations with high (82–90%) H1N1 VE provided significant protection from wt challenge, while formulations with reduced (19–32%) VE tended not to provide significant protection. The strongest correlation observed was between reduction in wt shedding and VE (R² = 0.75). Conversely, serum immunogenicity following vaccination was not a reliable indicator of protection (R² = 0.37). This demonstrated that, by optimisation of the vaccine dose and the use of non-serological, clinically relevant protection endpoints, the ferret model could successfully translate clinical H1N1 LAIV VE data. Full article

Background/Objectives: Live influenza vaccines are considered to stimulate better overall immune responses but are associated with safety concerns regarding shedding and the potential for transmission or reassortment with wild-type influenza viruses. Intranasal M2SR and BM2SR (M2- and BM2-deficient single replication), intranasal influenza viruses, have shown promise as broadly cross-reactive next-generation influenza vaccines. The replication deficiency, shedding, and transmissibility of M2SR/BM2SR viruses were evaluated in a ferret model. Methods: Wild-type influenza A and B control viruses replicated in upper respiratory organs and transmitted to both direct and aerosol contact ferrets, whereas M2SR and BM2SR influenza vaccine viruses were not detected in any tissues or in nasal washes after inoculation and were not recovered from any direct or aerosol contact ferrets. Mice were simultaneously infected with wild-type influenza A and M2SR viruses to assess reassortment potential. Sequence and PCR analyses of the genome recovered from individual virus plaques isolated from lung homogenates identified the origin of the segments as exclusively from the replicating wild-type virus. Results: These results indicate that M2SR and BM2SR influenza vaccine viruses are attenuated, do not shed or transmit, and have a low probability for reassortment after coinfection. Absence of shedding was further demonstrated in nasal swabs taken from subjects who were inoculated with H3N2 M2SR in a previously described Phase 1 clinical study. Conclusions: These results indicate that M2SR/BM2SR viruses have the potential to be used in a broader population range than current live influenza vaccines. Full article

Background. Influenza and SARS-CoV-2 viruses are two highly variable pathogens. We have developed a candidate bivalent live vaccine based on the strain of licensed A/Leningrad/17-based cold-adapted live attenuated influenza vaccine (LAIV) of H3N2 subtype, which expressed SARS-CoV-2 immunogenic T-cell epitopes. A cassette encoding fragments of S and N proteins of SARS-CoV-2 was inserted into the influenza NA gene using the P2A autocleavage site. In this study, we present the results of preclinical evaluation of the developed bivalent vaccine in a non-human primate model. Methods. Rhesus macaques (Macaca mulatta) (n = 3 per group) were immunized intranasally with 7.5 lg EID₅₀ of the LAIV/CoV-2 bivalent vaccine, a control non-modified H3N2 LAIV or a placebo (chorioallantoic fluid) using a sprayer device, twice, with a 28-day interval. The blood samples were collected at days 0, 3, 28 and 35 for hematological and biochemical assessment. Safety was also assessed by monitoring body weight, body temperature and clinical signs of the disease. Immune responses to influenza virus were assessed both by determining serum antibody titers in hemagglutination inhibition assay, microneutralization assay and IgG ELISA. T-cell responses were measured both to influenza and SARS-CoV-2 antigens using ELISPOT and flow cytometry. Three weeks after the second immunization, animals were challenged with 10⁵ PFU of Delta SARS-CoV-2. The body temperature, weight and challenge virus shedding were monitored for 5 days post-challenge. In addition, virus titers in various organs and histopathology were evaluated on day 6 after SARS-CoV-2 infection. Results. There was no toxic effect of the immunizations on the hematological and coagulation hemostasis of animals. No difference in the dynamics of the average weight and thermometry results were found between the groups of animals. Both LAIV and LAIV/CoV-2 variants poorly replicated in the upper respiratory tract of rhesus macaques. Nevertheless, despite this low level of virus shedding, influenza-specific serum IgG responses were detected in the group of monkeys immunized with the LAIV/CoV-2 bivalent but not in the LAIV group. Furthermore, T-cell responses to both influenza and SARS-CoV-2 viruses were detected in the LAIV/CoV-2 vaccine group only. The animals were generally resistant to SARS-CoV-2 challenge, with minimal virus shedding in the placebo and LAIV groups. Histopathological changes in vaccinated animals were decreased compared to the PBS group, suggesting a protective effect of the chimeric vaccine candidate. Conclusions. The candidate bivalent vaccine was safe and immunogenic for non-human primates and warrants its further evaluation in clinical trials. Full article