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Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne zoonotic pathogen with high mortality and no licensed vaccines. We developed two lipid nanoparticle-encapsulated mRNA vaccines encoding the Gn and Gc glycoproteins of SFTSV and evaluated their immunogenicity and protective efficacy in mice, as well as their immunogenicity in dogs. In mice, the Gn mRNA vaccine induced higher neutralizing antibody titers and stronger cellular immune responses than the Gc vaccine, and both conferred complete protection against lethal SFTSV challenge in IFNAR-blocked mice. In contrast, in dogs, the Gc mRNA vaccine elicited significantly higher neutralizing antibody titers than Gn, despite comparable safety profiles. This species-dependent divergence in immunogenicity underscores the importance of host-specific considerations in antigen selection for zoonotic vaccine development. These findings support the immunogenic potential of both constructs as candidate vaccines against SFTSV. In this study, we developed mRNA vaccines targeting the severe fever with thrombocytopenia syndrome virus Gn and Gc glycoproteins separately and systematically evaluated their immunogenicity in murine and canine models. Our findings demonstrate that both vaccine formulations effectively elicited potent neutralizing antibody responses in immunized animals. Notably, we observed distinct species-specific immunogenicity patterns: the Gn-targeted vaccine showed superior performance in a murine model, whereas the Gc-targeted variant induced more robust immune activation in beagles. These results emphasize that vaccine selection must account for species-specific efficacy.

Foot-and-mouth disease virus (FMDV) escapes host immune surveillance via adaptive evolution driven by vaccine-mediated selective pressure, leading to persistent breakthrough infections in immunized animals. In this study, the dominant neutralizing epitope VP1 G-H loop (141-160 aa) was analyzed among 46 serotype O FMDV strains belonging to Southeast Asian (SEA) and Middle East-South Asian (ME-SA) topotypes isolated during 1980-2019. The key amino acid residues at VP1 positions 142 and 153 underwent sequential stepwise evolution across three phases under natural selection. Based on the reverse genetic system of Wt, single-site mutant (T142P, Q153P) and double-site mutant (T142P&Q153P) strains were rescued. These mutation sites were further introduced into an efficient FMDV nanoparticle vaccine to construct four vaccine candidates. Mouse immunization verified all vaccines conferred solid protection against Wt and single-mutant strains, yet protection efficacy was greatly impaired against the double mutant. The double-mutant vaccine elicited high-level neutralizing antibodies against the double-mutant strain (T142P&Q153P) with a titer of 1:426.67, 10-20 folds higher than Wt (1:21.33), T142P (1:32), and Q153P (1:42.67) vaccines. Consistent results were also obtained in pigs immunized with commercial inactivated vaccines. Collectively, combined mutations at VP1 142 and 153 reshape viral antigenicity and act as core drivers of FMDV immune evasion. Integrating such immune escape hotspots into vaccine antigens can broaden neutralizing antibody coverage, offering an experimental basis for clarifying FMDV evolution and developing broad-spectrum vaccines.

The global aging population faces heightened vulnerability to infectious diseases due to immunosenescence, which diminishes the potency, durability, and breadth of vaccine-induced immunity. While the leading shingles vaccine, Shingrix, provides protection against herpes zoster virus for adults aged 50 and older, it is often associated with severe local and systemic reactogenicity, which limits vaccine compliance. Here, we report an injectable polymer-nanoparticle (PNP) hydrogel platform for the sustained delivery of a shingles subunit vaccine to enhance immune responses while mitigating reactogenicity in aged mice. Hydrogel-based vaccination elicited significantly more potent and durable humoral immune responses than Shingrix, while inflammatory cytokine levels remained below the limit of detection. Moreover, aged mice vaccinated with the hydrogel-based vaccine exhibited robust antigen-specific cellular immune responses. These findings demonstrate that controlling the temporal presentation of vaccine components can overcome age-associated declines in immune responsiveness without inducing excessive inflammatory signaling. By decoupling immunogenicity from reactogenicity, our hydrogel-based delivery strategy offers a promising approach to improve both the efficacy and tolerability of subunit vaccines for the elderly and may be broadly applicable to other vaccines targeting aging populations.

Staphylococcus aureus is a major global health threat due to its increasing antibiotic resistance and high virulence, presenting serious challenges in healthcare. Currently, no effective vaccine exists to prevent its infections. In our study, we introduced a novel multi-epitope vaccine design method using immunoinformatics, named the "Just the Best Ones" strategy. This approach involved selecting the most promising T-cell and B-cell epitopes from 10 key proteins of S. aureus based on the pathogenic mechanism of the bacterium in the host, to create the Staphylococcus aureus Multi-Epitope Antigen (SAMEA) with optimal immunogenicity. Physicochemical and structural analyses confirmed SAMEA's stability and suitable profiles for antigenicity, toxicity, and allergenicity. Molecular docking showed strong interactions between SAMEA and human TLR2, crucial for eliciting effective immune responses. Additionally, SAMEA was highly immunogenic and safe, generating a strong antibody response and excellent protection in mice. These results suggest that SAMEA is a promising multi-epitope vaccine candidate, highlighting the "Just the Best Ones" strategy's effectiveness, and introducing a new direction in vaccine development against S. aureus infections. Methicillin-resistant Staphylococcus aureus (MRSA) is a major health threat due to its antibiotic resistance and ability to cause severe infections in humans and animals. Yet, no licensed vaccine is available. Here, we present a "Just the Best Ones" strategy that applies immunoinformatics to select the most protective epitopes from key S. aureus antigens. Using this approach, we developed a multi-epitope antigen (SAMEA) that proved safe, highly immunogenic, and protective in mice, particularly when combined with a bacterium-like particle adjuvant. These results highlight SAMEA as a promising MRSA vaccine candidate and indicate that this strategy may help guide vaccine development for other difficult pathogens. As it continues to be refined, this approach could facilitate more effective vaccines and improve the prevention of infectious diseases.

Five vaccination-challenge trials were performed with a live attenuated vaccine which includes an infectious bronchitis virus (IBV) Massachusetts strain (H120, GI-1), an IBV Q1 strain (BNF 28/86, GI-16), and a Newcastle disease virus (NDV) cloned strain. The efficacy of the vaccine was tested in maternally-derived antibody-positive (MDA+) commercial layers against challenge with IBV M41, 793B, D388(QX) or Q1 challenge virus. The efficacy of the vaccine was also tested in SPF layers against challenge with IBV M41, D388(QX) or Variant 2 challenge virus. The vaccine was applied at day of hatch, and all challenges were performed at 3 weeks of age. At 5 days post-challenge, the ciliary activity of tracheal explants was examined to determine the level of protection. The level of protection induced by the vaccine in commercial layers against IBV M41, 793B, D388(QX) and Q1 challenge was 91%, 94%, 73% and 84%, respectively. The level of protection in the SPF layers against IBV M41, D388(QX) and Var2 challenge was 89%, 69%, and 96%, respectively. In summary, vaccination with a live attenuated vaccine which includes an IBV Massachusetts strain (H120, GI-1) and an IBV Q1 strain (BNF 28/86, GI-16) provides a substantial level of protection against the homologous and most heterologous challenge viruses, which are representatives of the IBV strains circulating worldwide.

Enteric viral infections remain a major cause of morbidity and mortality worldwide, particularly in children and intensively raised livestock. Although live oral vaccines have reduced disease burden, vaccine efficacy varies greatly across regions. Factors such as host genetics, microbiota, maternal antibodies, and nutrition have been widely studied, whereas chronic exposure to dietary toxicants has received less attention. Mycotoxins, fungal metabolites contaminating staple crops including maize, wheat, and peanuts, are commonly consumed at low but persistent levels in regions heavily affected by enteric viral diseases. Increasing evidence shows that mycotoxins disrupt intestinal barrier integrity, alter innate and adaptive immune responses, and reshape gut microbial ecology even without overt toxicity. These effects target pathways essential for antiviral defense and oral vaccine efficacy. This review proposes a mechanistic framework in which chronic mycotoxin exposure alters epithelial-immune-microbiota interactions, thereby increasing susceptibility to enteric viral infection and reducing vaccine-induced protection. We summarize evidence linking mycotoxins to barrier dysfunction, interferon dysregulation, antigen-presenting cell impairment, IgA suppression, intestinal stem cell injury, and microbiota-mediated changes in viral infectivity. Recognizing mycotoxins as covert regulators of mucosal antiviral immunity may provide new strategies to improve oral vaccine performance and reduce global enteric viral disease burden.

Salmonella enterica serovars (Salmonella) are common causes of bacterial gastroenteritis (salmonellosis) often associated with the consumption of poultry products. The control of Salmonella in broiler chickens is difficult because colonized birds may carry this pathogen undetected into the slaughterhouse and cause meat contamination. Poultry vaccines can mitigate colonization, and one promising production method is via plants. Iron is an essential nutrient for Salmonella; therefore, our goal was to exploit iron uptake systems as vaccine targets that could starve this pathogen of iron and thus prevent it from colonizing chickens. One challenge with this approach is that Salmonella possesses several iron acquisition proteins that are redundant in function. Therefore, we created nanoparticle-based plant-produced vaccine candidates against four different Salmonella iron acquisition proteins to create a multivalent vaccine that may be more effective than targeting a single protein. Extracellular antigenic peptides from each of these proteins were fused in tandem to the N-terminus of the self-assembling Brucella spp. lumazine synthase. These fusion constructs were then expressed in Nicotiana benthamiana plants. The resulting recombinant proteins were extracted, purified and characterized. The vaccine candidates administered individually or in combination elicited specific antibodies in mice and bound to the surface of Salmonella, indicating their potential in preventing Salmonella colonization in poultry.

Blastocystis sp. is a neglected, globally prevalent intestinal parasite infecting over one billion people with no available vaccine. This study describes an immunoinformatics framework for developing a multi-epitope subunit vaccine against &#x3b1;-L-fucosidase from Blastocystis sp. Immunogenic B-cell and T-cell epitopes were identified through systematic prediction and rigorous allergenicity, toxicity, and human homology screening. Epitopes were assembled into a vaccine with human &#x3b2;-defensin-3 as an N-terminal adjuvant. The vaccine displayed favorable physicochemical properties including optimal molecular weight (~&#x2009;38&#xa0;kDa), stability index (<&#x2009;40) and negative GRAVY score. Population coverage analysis achieved 97.13% global coverage with 24.75 epitope-HLA hits per individual and a PC90 of 14.42. Structural validation of predicted 3D structure using Ramachandran analysis (99.7% residues in favored regions) and ProSA-web evaluation (Z-score:&#x2009;-&#x2009;5.07) confirmed high-quality tertiary structure. Molecular docking revealed extensive binding with TLR-4, MHC Class I, and MHC Class II receptors, with interface areas of 1379-2198 &#xc5;2 and 13-19 hydrogen bonds per complex. VD-MM/GBSA analysis reported favorable binding energies (-&#x2009;295 to&#x2009;-&#x2009;370&#xa0;kcal/mol), while NMA confirmed appropriate dynamic flexibility for biological activity. Immune simulations predicted robust humoral and Th1-biased cellular responses with sustained IgG/IgM antibody production and maintained immune homeostasis. In silico cloning into pET-28a(&#x2009;+) showed optimal codon adaptation (CAI: 0.97) and GC content (53.31%), providing a pathway toward experimental validation of the first Blastocystis vaccine.

To provide an update paper on evidence of adverse events of concern following immunization (AEFI) with pertussis vaccines, focusing primarily on acellular (aP) vaccines. Evidence was synthesised from epidemiological studies, systematic reviews over recent decades, expert interpretations in reviews from relevant research teams and well-conducted observational reports across different time periods. A more comprehensive review of the literature was conducted for certain specific AEFIs, including sterile abscesses, macrophagic myofasciitis, reactions to aluminium adjuvants, Guillain-Barr&#xe9; syndrome, acute disseminated encephalomyelitis (ADEM) and anaphylaxis. Acellular (aP) vaccines are generally associated with mild reactions such as local pain, redness, and transient fever. Moderate reactions, including prolonged crying, hypotonic-hyporesponsive episodes, extensive limb swelling, and aluminium-induced granuloma, occur infrequently and are self-limiting. Severe outcomes such as seizures or encephalopathy have been extensively investigated, with large studies showing no consistent increase above background incidence. Licensed acellular pertussis vaccine combinations demonstrate acceptable safety profiles, with serious adverse events being rare. Continuous pharmacovigilance and balanced, evidence-based communication remain essential to sustain trust in pertussis immunisation programmes.

A 77-year-old woman was being treated for rheumatoid arthritis with prednisolone, methotrexate, and iguratimod. The patient was administered a live-attenuated varicella vaccine (Oka strain) for herpes zoster prevention by a primary care physician. Four weeks later, a vesicular rash appeared on the body. The patient was treated with amenamevir, and the rash improved. Based on the pathological findings and viral genotyping, she was diagnosed with a vaccine-induced disseminated varicella-zoster virus infection. For herpes zoster vaccination, caution is warranted as some medical questionnaires for vaccination do not include glucocorticoid use or immunosuppressive therapy, and some primary care physicians administer live vaccines only.

The coronavirus disease 2019 (COVID-19) pandemic has highlighted a complex, bidirectional relationship between SARSCoV-2 infection and autoimmune diseases. This review examines how SARS-CoV-2 infection influences the incidence, progression, and outcomes of five major autoimmune conditions: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and Guillain-Barr&#xe9; syndrome. Patients with autoimmune diseases are at increased risk of severe COVID-19 due to intrinsic immune dysregulation and the use of immunosuppressive therapies, both of which impair antiviral host defenses. Conversely, COVID-19 has been implicated in the initiation and exacerbation of autoimmune responses through mechanisms such as molecular mimicry and bystander activation. Concerns have also arisen regarding the safety and efficacy of COVID-19 vaccines in immunocompromised populations. Although vaccines are generally tolerated in these individuals, certain immunosuppressive therapies may attenuate humoral and cellular immune responses. Strategies such as adjusting immunosuppressive regimens and optimizing the timing of vaccination have been proposed to improve vaccine efficacy. Disease-specific considerations are essential to balance infection risk with adequate control of autoimmune activity. Overall, this review underscores the importance of individualized treatment strategies, close clinical monitoring, and interdisciplinary care in managing patients with autoimmune diseases during the COVID-19 pandemic. A deeper understanding of these interactions will be critical for improving patient outcomes and preparing for future pandemics involving immune-mediated diseases.

Malaria remains an infectious disease of global health concern. Recent approval and implementation of two vaccines for use for prevention of Plasmodium falciparum malaria in children in the African region is predicted to significantly reduce the burden of this disease. However, efforts are still required to improve efficacy and durability of these vaccines in target populations, and many other challenges remain to achieve malaria eradication. These include emergence and predominance of non-falciparum malaria in countries nearing elimination of P. falciparum, resurgences in malaria-free settings, and impacts of changing populations and ecology on transmission. Novel tools are needed to target neglected Plasmodium species, notably Plasmodium vivax, the second most common cause of human malaria. Plasmodium infections induce robust immune responses, meaning Plasmodium-specific antibodies can be used as both surveillance tools and as markers of immunity to clinical disease. In this mini-review, we discuss these use cases of malaria serology. We detail the concept behind serological surveillance and the need to understand antibody longevity, and discuss the application of this approach in endemic countries for both improved surveillance and as an intervention, with a focus on P. vivax while touching on other neglected Plasmodium species. People living in malaria-endemic areas naturally gain clinical immunity to malaria, meaning sero-epidemiological studies can also be used to understand the targets and functions of protective immunity. We review new studies on protective immunity, covering research on both P. falciparum and P. vivax, and highlight how these findings can be leveraged to maximize existing and novel vaccine design.

In 1999, the Centers for Disease Control and Prevention (CDC) established the New Vaccine Surveillance Network (NVSN) as a multi-site pediatric infectious diseases active surveillance system. NVSN prospectively collects population-based clinical, epidemiologic, and laboratory information on children who seek medical care at hospitals, emergency departments, urgent care centers, and outpatient clinics with symptoms of acute respiratory infections (ARI) and acute gastroenteritis (AGE) in the United States. These efforts have clearly established the significant burden of both ARI and AGE in US children, demonstrated the effectiveness of licensed pediatric vaccines, and helped guide their use. The surveillance platform also measures the real-world impact of preventive measures intended to avoid or ameliorate adverse child health outcomes within the US healthcare system. Furthermore, NVSN provides a platform for detecting and evaluating emerging infections (e.g. enterovirus D-68, SARS-CoV-2) and unexpected sequelae in children. For 25 years NVSN has provided an evidence-based foundation for pediatric infectious disease policy decision-making through objective, empirical data. Sustained investment in disease surveillance guides the scientific principles and public health practices that prevent suffering and premature death, prepares us for new and existent pathogen threats, and enables wise economic decisions that improve the health of Americans.

Lancefield Group C Streptococcus dysgalactiae recently emerged as a catfish pathogen in the US. Reports from hatcheries suggest S.&#x2009;dysgalactiae causes substantial broodfish loss. We aimed to develop a challenge model and evaluate vaccine efficacy against S.&#x2009;dysgalactiae in juvenile channel catfish (Ictalurus punctatus). Three S.&#x2009;dysgalactiae (14-1, 14-24 and 14-25) isolates were tested for virulence. Intracoelomic (IC) injection demonstrated S.&#x2009;dysgalactiae 14-1 was the most virulent. Reisolated 14-1 was used to develop a formalin-killed cell (FKC) vaccine. Catfish (200) were immunized via IC injection of 100&#x2009;&#x3bc;L FKC with adjuvant (1:1&#x2009;v/v), and another 200 catfish were sham vaccinated. Five fish from each group were bled for antibody titre every 14&#x2009;days. At 28 and 56&#x2009;days post-vaccination (dpv), subsets of both groups were challenged with S.&#x2009;dysgalactiae via IC injection (200&#x2009;&#x3bc;L/fish) in triplicate (20 fish/tank). Cumulative percent mortality was significantly (p&#x2009;<&#x2009;0.05) higher in sham (46.67% and 23.33%) than vaccinated fish (5.00% and 5.00%) at 28 and 56&#x2009;dpv, respectively. Relative percent survival in vaccinated groups was 89.3% at 28&#x2009;dpv and 78.6% at 56&#x2009;dpv. Conclusively, the adjuvanted S.&#x2009;dysgalactiae bacterin induced humoral immunity and protected juvenile catfish. Future studies are planned to evaluate this bacterin in broodfish.

We know that vaccine hesitancy is closely related to distrust in health organisations, pharmaceutical industry or governments (Vuolanto et al. 2024). At the end of the book, I am left with the question what is necessary to bridge the gap of distrust and how this relates to discussions on coercive measures. Intuitively, it seems necessary to understand the different types of distrust non-compliant parent groups have and Pierik and Verweij discuss these in Chapter 3 in order to offer tailored approaches to build trust. In Chapter 9, Pierik and Verweij discuss the lack of trust more specifically, but I question if their approach is well thought through: they are ambivalent on a so-called information deficit perspective on trust, which they reject and also seem to assume at the same time. I will first look at the various sources of distrust that Pierik and Verweij distinguish before I discuss their view on trust and trustworthiness.