Search Results (149)

Bundibugyo virus disease, caused by Bundibugyo virus (Orthoebolavirus bundibugyoense), is a severe human Ebola disease with substantial mortality, unresolved reservoir ecology, limited diagnostic implementation, and no licensed vaccines or therapeutics specifically approved for this Orthoebolavirus species. The May 2026 public health emergency in the Democratic Republic of the Congo and Uganda renewed the need for a focused synthesis of Bundibugyo virus-specific diagnostics and medical countermeasures. This review synthesizes the peer-reviewed literature, preprints, and official public-health documents on diagnostics, antivirals, therapeutics, vaccines, and post-exposure prophylaxis. Comparative evidence from the Ebola virus, Sudan virus, Marburg virus, and pan-filovirus platforms is included only where it clarifies Bundibugyo virus-specific evidence, exposes unsupported extrapolation, or defines preparedness gaps. The 2007–2008 outbreak showed that assays optimized for known filoviruses can miss divergent ebolaviruses; the 2026 outbreak underscored the importance of diagnostic breadth, sequencing-based confirmation, decentralized laboratory capacity, and regional coordination. Clinical and immunological data indicate that Bundibugyo virus cannot be reduced to an Ebola virus-like model. Countermeasure evidence remains largely preclinical: recombinant vesicular stomatitis virus vaccines expressing Bundibugyo virus glycoprotein provide the strongest direct animal protection data, whereas antiviral and antibody-based evidence varies widely and requires careful separation of direct Bundibugyo virus data from platform-based extrapolation. Full article

Proteins are the most common targets for antibody discovery and vaccine development, but their sequence variability can limit the breadth of resulting antigens. Lipids represent an alternative class of antigens due to their structural conservation and roles in host–pathogen interactions. Here, we describe the development and optimization of an in vitro antibody selection workflow using lipid-containing nanodiscs as antigen presentation platforms to enable phage and yeast display selections under conditions adapted for these non-protein targets. Lipopolysaccharide (LPS) nanodiscs were first used as a model system to evaluate selection strategies, including competitive and subtractive approaches to reduce non-specific binders, yielding peptide and single-chain variable fragment (scFv) binders that were affinity matured to improve binding signals. The same approach was subsequently used to select scFv antibodies that recognize lipid nanodiscs prepared from Yersinia pestis membrane lipid extracts. These antibodies show binding to lipid nanodiscs derived from Y. pestis, with evidence of selectivity relative to control nanodiscs. Overall, this work establishes a workflow for antibody selection against lipid-containing nanodisc antigens and highlights practical considerations associated with these targets. The approach may be useful for generating affinity reagents to membrane-associated lipids, although further characterization is required to define antigen specificity and functional activity. Full article

Porcine enteric coronaviruses (PECs), including porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV), remain major causes of neonatal diarrhea, dehydration, mortality, and economic loss in swine production. Despite substantial progress in vaccine development, durable field protection is still inconsistent. In this narrative review, this narrative review synthesizes current knowledge on PEC vaccine design from three connected perspectives: antigenic breadth, mucosal immunity, and translational evaluation. The economic and virological context of PEC vaccine development is first summarized, including the recurrent production burden of PECs, coronavirus genome organization, structural proteins, and the central role of the spike protein in receptor engagement, membrane fusion, and neutralizing antibody induction. Key issues are then discussed, including how spike diversity, conformational stability, epitope accessibility, glycan shielding, and antigen matching influence protective breadth; why intestinal secretory IgA, mucosal immune-cell trafficking, local memory responses, and lactogenic immunity should be prioritized as biologically relevant endpoints; and how delivery route, adjuvant selection, and platform design shape response quality. Current evidence on recombinant protein, viral-vectored, nanoparticle, virus-like particle, probiotic, plant-derived, and mRNA-based approaches is compared with attention to both promise and current evidentiary and translational limitations. The available literature suggests that future progress in PEC vaccinology is likely to depend less on platform novelty alone than on integrated vaccine designs that align antigen selection, mucosal delivery, maternal–neonatal protection, heterologous challenge, manufacturability, and field applicability. Full article

Henipaviruses (HNVs), including Nipah virus (NiV) and Hendra virus (HeV), are highly pathogenic and often lethal zoonotic viruses with broad species tropism and no approved human vaccines. The emergence of genetically divergent HNVs—including Ghana virus (GhV), Langya virus (LayV), and Mojiang virus (MojV)—emphasizes the need for broadly protective countermeasures. Here, we evaluated the antibody (Ab) responses to sequential mRNA vaccines encoding the membrane-bound attachment glycoprotein (gG) from NiV, GhV, and/or LayV in a pilot study with Indian rhesus macaques. Serum binding Ab responses were quantified by ELISA against five soluble gG antigens (NiV, HeV, GhV, LayV, MojV). Functional activity was assessed by neutralization assays using NiV, HeV, and GhV pseudoviruses, and by receptor-blocking ELISA. Sequential vaccination induced high-titer IgG binding against all five HNV gGs with increasing breadth after each dose. Pan-genus regimens elicited moderate neutralizing Ab titers against NiV, HeV, and GhV, whereas the NiV-only regimen elicited potent but narrow neutralization against NiV and HeV. Conversely, the GhV-LayV-GhV regimen elicited strong binding to GhV, LayV, and MojV gG and robust neutralization of GhV pseudovirus, but limited cross-reactivity to NiV and HeV. In this pilot study, we demonstrated that mRNA vaccination can elicit broadly reactive binding and neutralizing Ab responses across phylogenetically distant HNVs. Additionally, we show GhV pseudovirus neutralization for the first time. Collectively, these data provide a foundation for the development of next-generation pan-genus HNV vaccines capable of mitigating future HNV outbreaks. Full article

Background: People living with HIV (PLWH) constitute a vulnerable population during the COVID-19 pandemic; however, it remains uncertain whether long-term suppressive antiretroviral therapy (ART) restores sufficient immune competence to support robust hybrid immunity. While vaccination followed by breakthrough infection—termed hybrid immunity—typically elicits potent humoral responses in immunocompetent individuals, the functional quality and breadth of these responses against evolving Omicron subvariants remain poorly characterized in PLWH. This study aimed to assess functional antibody responses, including neutralizing activity and Fc effector functions, in vaccinated and unvaccinated PLWH who experienced breakthrough infection with Omicron subvariants BA.4/5 or BF.7. Methods: We enrolled three cohorts between December 5 and December 20, 2022: 25 HIV-negative individuals with breakthrough infection (BTI-HC), 20 ART-experienced PLWH with breakthrough infection following three-dose COVID-19 vaccination (BTI-HIV), and 10 ART-experienced PLWH with primary infection without prior vaccination (PI-HIV). All HIV-positive participants were receiving suppressive ART with regimens based on non-nucleoside reverse transcriptase inhibitors or integrase strand transfer inhibitors for a median of 3.4 years. We measured receptor-binding domain (RBD)-specific IgG, neutralizing antibody titers against ancestral D614G, Delta, BA.1, BA.4/5, BF.7, XDV, KP.2, and KP.3 variants, and antibody-dependent cellular cytotoxicity (ADCC) responses. Results: Despite lower absolute CD4⁺ T cell counts, BTI-HIV participants mounted RBD-binding IgG, neutralizing antibody, and ADCC responses that were comparable to BTI-HC and significantly exceeded PI-HIV across all tested variants. Both breakthrough infection cohorts exhibited immunological imprinting, with higher neutralizing titers against ancestral D614G than infecting BA.4/5 or BF.7 variants. Emerging variants XDV, KP.2, and KP.3 demonstrated substantial neutralization escape in all groups. PI-HIV showed markedly diminished neutralization breadth and failed to generate enough responses against all tested Omicron strains. Conclusions: Suppressive ART enables PLWH to mount hybrid immunity—conferred by vaccination followed by BF.7 or BA.4/5 breakthrough infection—with neutralizing and ADCC responses comparable to HIV-negative individuals, and significantly exceeding those of unvaccinated PLWH with primary infection. This underscores the critical role of vaccination in establishing effective hybrid immunity in this population. However, we observed immunological imprinting, with higher titers against ancestral strains than against infecting variants, and substantial escape by emerging sublineages XDV, KP.2, and KP.3 across all groups. These findings support prioritizing updated variant-containing vaccines for HIV-positive populations and reinforce the essential role of vaccination in this vulnerable group. Full article

Background/Objectives: Influenza, RSV, and SARS-CoV-2 co-circulate and evolve under immune and therapeutic pressures, complicating decision-making for both vaccine formulation and antiviral use. Fragmented, pathogen-specific sequencing approaches limit cross-virus comparability. Methods: We applied a standardized, multiplexed, amplicon-based next-generation sequencing (NGS) workflow to 34 diagnostic specimens (Ct < 35) positive for influenza A/B, RSV-A/B, or SARS-CoV-2. Sequencing libraries were generated and run on an Illumina MiSeq platform (2 × 250 bp). Although the wet-lab workflow is standardized across pathogens, consensus generation and annotation utilized two different analysis environments: Geneious Prime for influenza and MicrobioChek for RSV and SARS-CoV-2. Quality metrics included genome breadth and depth of coverage. Results: Near-complete genomes (mean coverage ≥98%) were recovered for all samples. Influenza A(H1N1)pdm09 sequences clustered in clade 6B.1A; A(H3N2) clustered in subclade 3C.2a1b.2a.2; and influenza B belonged to the Victoria lineage V1A.3a.2. RSV sequences were assigned to Nextclade clades A.D.5.1, A.D.1.10, A.D.2.1, and A.D.3 (RSV-A) and to B.D.4.1.3 and B.D.E.1 (RSV-B), consistent with the ON1 (RSV-A) and BA (RSV-B) genotypes prevalent in recent seasons. Clinically relevant mutations included changes in the influenza HA site and neuraminidase substitutions, RSV F-protein polymorphisms, and spike protein substitutions associated with recent Omicron sublineages (L455F/S, F456L) in SARS-CoV-2. Conclusions: A unified amplicon–NGS approach yields harmonized genomic data across respiratory viruses, enabling timely detection of antigenic drift and resistance markers while supporting integrated, cross-pathogen surveillance. Full article

Human T-cell leukemia virus type-1 (HTLV-1) is endemic to numerous regions worldwide, including Central Australia. The Australo-Melanesian subtype-C is endemic within Australia and Oceania, whereas subtype-A is the most widely distributed subtype globally. The lack of an approved vaccine highlights HTLV-1 as a neglected public health issue. To inform the development of HTLV-1 Envelope (Env)-based vaccines, we assessed anti-Env antibodies in an HTLV-1c+ cohort of First Nations individuals in Central Australia. Of the 62 plasma samples from patients with confirmed HTLV-1 serological diagnosis, 76% were positive for Env binding in ELISA, but 90% neutralized HTLV-1c pseudovirus (PSV) infection. Neutralization breadth with the capability of blocking both subtype-A and subtype-C PSV infection was identified in 100% of samples tested. Proviral load was positively associated with anti-Env response, with binding epitopes mapping to the proline-rich region of gp46-SU. Env-directed IgG showed the capacity to engage Fcγ receptors key to inducing antibody-dependent cellular cytotoxicity/phagocytosis responses. Serological response was not associated with comorbidities linked to HTLV-1c in this population (bronchiectasis, chronic kidney disease, diabetes). These findings demonstrate that potent humoral immunity arises and is sustained during HTLV-1 infection, suggesting that an Env-based vaccine displaying authentically native epitopes will be capable of recapitulating these neutralizing responses. Full article

Background/Objectives: Coronaviruses are a family of positive-sense RNA viruses that cause respiratory and gastrointestinal disease in mammals and birds. Their zoonotic nature and high mutability make them a pandemic threat. UNICOR-v is a pre-pandemic, pan-coronavirus vaccine composed of an adjuvanted mix of twelve synthetic peptides originating from conserved regions within Nsp12 and M coronavirus proteins containing clusters of predicted T-cell epitopes. Here, we evaluate the immunogenicity of UNICOR-v and its efficacy against Middle East Respiratory Syndrome-related coronavirus (MERS). Methods: Animals were vaccinated with an adjuvanted equimolar mix of UNICOR-v. Humoral and cellular immunogenicity were assessed 28 days later through ELISA and FLUOROSpot. Vaccine efficacy was assessed in a DPP4 knock-in (HDPP4-KI) mouse model where mice were challenged post-vaccination with a lethal or non-lethal dose of MERS-CoV-MA. Results: Vaccination with UNICOR-v induced high IgG titers in both mice and rabbits and cellular secretion of pro-inflammatory cytokines. Vaccination with UNICOR-v, or passive serum transfer, significantly reduced viral lung titers 4 days post-infection compared to placebo. Vaccination induced lower immune cell infiltration in the alveolar space and increased repair of the cells lining the major airways in vaccinated mice, translating to increased survival rate compared to placebo. Conclusions: These data demonstrate the ability of conserved T-cell epitopes to protect against MERS-CoV infection, supporting further characterization of the breadth of protection of UNICOR-v against other coronaviruses that affect humans and livestock, following a One Health approach to control this highly zoonotic family of viruses. Full article

Porcine reproductive and respiratory syndrome (PRRS) remains one of the most economically devastating diseases in global swine production. The causative agent, PRRS virus (PRRSV), comprises two genetically distinct species—PRRSV-1 and PRRSV-2—that differ substantially in antigenic composition and immune recognition. Despite widespread use of modified live vaccines (MLVs), protection against heterologous and cross-species strains remains inconsistent and difficult to predict. This review synthesizes current knowledge of homologous, heterologous, and cross-species protection, with emphasis on humoral and cellular immune responses and the viral determinants that constrain breadth of immunity. Neutralizing antibodies can confer near-sterilizing homologous protection under controlled conditions; however, their delayed induction and narrow specificity limit efficacy against heterologous strains. T-cell-mediated responses are generally broader but remain highly strain- and context-dependent. Structural features of PRRSV envelope glycoproteins, including glycan shielding and immunodominant decoy epitopes, further restrict antibody-mediated cross-protection while providing targets for rational vaccine design. We also examine potential drawbacks of preexisting immunity, including antigenic mismatch and non-neutralizing antibody-dominated responses that may contribute to suboptimal outcomes following heterologous exposure. Collectively, these findings highlight the multifactorial nature of PRRSV protection and the need for next-generation vaccines capable of inducing broader and more durable immunity. Full article

As SARS-CoV-2 continues to evolve with increased transmissibility and immune evasion, the need for vaccines that provide broader and more durable protection has become increasingly urgent. The extensive research spurred by the pandemic has accelerated the development of diverse vaccine platforms, including mRNA, DNA, virus-like particles (VLPs), recombinant proteins, and mosaic mono- and polyvalent vaccines. While several of these platforms have reached regulatory approval and widespread clinical employment, others remain under evaluation or in various stages of clinical development. These vaccines have significantly reduced infection rates, severe disease, and hospitalizations, particularly among high-risk group. Nevertheless, the ongoing emergence of novel variants and subvariants has challenged the efficacy of both existing and newly developed vaccines. This evolving landscape underscores the urgent need for a universal SARS-CoV-2 vaccine platform capable of providing comprehensive and long-lasting immunity. In this review, we evaluate current and emerging strategies for SARS-CoV-2 universal vaccine development, with a focus on antigen design, breadth of immune protection, and clinical feasibility. Attention is given to various universal vaccine platforms such as the mosaic polyvalent spike construct, multi-epitope vaccines targeting the receptor-binding domain (RBD), and approaches centered on the conserved S2 subunit of the spike protein. We also discuss strategies leveraging additional conserved viral proteins and T helper (Th) and cytotoxic T lymphocyte (CTL) epitopes from across coronaviruses. By highlighting the advances in these areas, this review provides a framework to guide the rational design of next-generation universal vaccines capable of delivering broad and durable protection against SARS-CoV-2 variants. Full article

Nationwide hospital discharge databases are increasingly used in infectious disease research, yet their methodological strengths and limitations are rarely synthesised. In Spain, the Minimum Basic Data Set (Conjunto Mínimo Básico de Datos, CMBD) was implemented in 1987 and provides near-universal coverage of acute-care hospitalisations and has been widely applied in infectious disease epidemiology. However, its overall contribution and intrinsic constraints have not been comprehensively mapped. Given the breadth of infections, study designs, populations and outcome definitions in CMBD-based research, effect-size synthesis was not feasible; therefore, we conducted a scoping review with an evidence-mapping approach. We aimed to synthesise the scope, applications and methodological limitations of CMBD-based infectious disease research since its implementation. We conducted a scoping review following JBI guidance and reported according to PRISMA-ScR. PubMed, Embase, Web of Science and Scopus were searched from inception to 25 November 2024 for peer-reviewed journal articles in English or Spanish using CMBD data to investigate infectious diseases in Spain (no restrictions were applied by study design; grey literature was excluded). Screening, data charting and synthesis were completed during 2025. Four reviewers independently screened records and charted data. Studies were classified by infectious disease focus, syndromic category, study design and geographical scope. A total of 359 studies published between 1996 and 2024 were included, mostly retrospective observational analyses. Infectious diseases were the primary focus in 225 studies (62.7%), most commonly respiratory, gastrointestinal/liver and vaccine-preventable infections. Subnational analyses were concentrated in a limited number of regions. Over 80% of reported limitations reflected intrinsic CMBD features. Over three decades, the CMBD has become a cornerstone of hospital-based infectious disease research in Spain, enabling robust national analyses. However, limitations in clinical detail, microbiological confirmation and coding consistency constrain aetiological specificity and causal inference, highlighting the need for data validation and linkage with complementary sources. Full article

The development of a universal SARS-CoV-2 vaccine holds great promise for achieving broad and durable protection against existing and future coronavirus variants. The identification, selection, and rational redesign of conserved viral epitopes constitute the direct immunological foundation of universal SARS-CoV-2 vaccine development. The breadth and durability of protection are therefore primarily determined at the level of antigen and epitope design, whereas adjuvants, delivery platforms, and routes of administration serve as enabling and amplifying components rather than primary drivers of universality. Accordingly, this review discusses key determinants of universal vaccine design, including antigen selection, adjuvant utilization, and route of administration. The spike protein, particularly its receptor-binding domain, is a major antigenic target, but its high mutation rate challenges long-term vaccine efficacy. Strategies focusing on conserved epitopes in antigen designs show potential to elicit cross-neutralizing immune responses. Nanoparticle-based vaccines capable of presenting multiple homologous or heterologous antigens have demonstrated enhanced immunogenicity, broad protection in preclinical models and safety in clinical trials. The addition of next-generation adjuvants further amplifies humoral and cellular immunity beyond the capabilities of traditional aluminum-based adjuvants. Moreover, mucosal vaccine delivery may provide superior local protection at viral entry sites and limit transmission. Importantly, integrating these technological advances with epitope-centered antigen design and immunological data from vaccinated individuals will accelerate the identification of conserved epitopes and inform future vaccine design. A multidisciplinary approach combining optimized antigen engineering, novel adjuvant systems, and innovative delivery strategies is essential for the realization of a broadly protective universal SARS-CoV-2 vaccine. Full article

Variant emergence continues to pose a threat to public health, despite the widespread use of vaccination. To quantify how vaccine strain compositions shape evolutionary and epidemiological outcomes, we extend a previous genotype-structured transmission model with vaccination and study the impact of different vaccination formulations on variant emergence. It consists of a set of partial differential equations coupled with an integro-differential one. We begin by showing that the model reproduces variant emergence followed by a period of co-circulation in the absence of vaccination. Then, we introduce vaccination and show important trade-offs shaped by the breadth and cross-protection of vaccine-induced immunity. In our simulations, narrow-spectrum vaccines substantially reduce the immediate infection burden but inadvertently promote the emergence of non-targeted variants. After that, we study the effects of more complex shapes such as triangular and M-shaped configurations. We show that M-triangular distributions outperform triangular ones by limiting secondary variant expansion for vaccines with narrow cross-protection. In contrast, triangular compositions are more protective when considering broader cross-protection. We also show that targeting the genetic area between co-circulating variants is more beneficial than focusing on specific variants when using vaccines with a broad cross-protection. Together, these results highlight how vaccine breadth and antigenic targeting influence both epidemic size and the trajectory of variant emergence, offering quantitative guidance for monovalent and multivalent vaccine design. Full article

Mycoplasma pneumoniae is traditionally recognized as a leading cause of community-acquired pneumonia, yet growing evidence demonstrates that its clinical impact extends far beyond the respiratory tract. Increasing reports of neurologic, cardiac, hematologic, dermatologic, renal, gastrointestinal, and thrombotic complications indicate that M. pneumoniae should be viewed as a systemic pathogen capable of inducing multisystem disease. Extrapulmonary manifestations may arise through three major mechanisms: direct bacterial invasion of tissues, immune-mediated injury driven by molecular mimicry or immune complexes, and vascular or thrombotic events related to endothelial dysfunction. These processes frequently occur independently of, or temporally dissociated from, respiratory symptoms, complicating early diagnosis. The diagnostic approach remains challenging because respiratory PCR may reflect colonization, serology is delayed, and pathogen detection in sterile sites is uncommon. Consequently, diagnosis often depends on the integration of clinical features, laboratory markers, and organ-specific imaging. Management requires a combined strategy: antimicrobial therapy to reduce bacterial load, organ-targeted supportive measures, and immunomodulatory interventions such as corticosteroids, IVIG, or plasma exchange for severe immune-mediated complications. The emergence of macrolide-resistant strains further underscores the need for tailored antimicrobial strategies and close clinical monitoring. Although many extrapulmonary complications are reversible, severe forms—including encephalitis, ADEM, myocarditis, Stevens–Johnson syndrome, and major thromboses—can lead to lasting morbidity or death. Significant knowledge gaps persist, including determinants of host susceptibility, mechanisms linking CARDS toxin to systemic inflammation, the impact of macrolide resistance on disease severity, and the absence of standardized diagnostic criteria. Advances in molecular immunology, multicenter registries, and development of targeted therapies or vaccines represent crucial next steps. Overall, the breadth and clinical relevance of extrapulmonary involvement support a paradigm shift: Mycoplasma pneumoniae infection should be regarded and managed as a systemic disease rather than a purely respiratory pathogen. Full article

Spatial transcriptomics (ST) enables genome-wide gene expression profiling while preserving tissue architecture, bridging the gap between bulk, single-cell, and histological analyses. Originating in 2016 and rapidly evolving since, ST has transformed infectious disease research by mapping host–pathogen interactions directly within intact tissues. Current platforms fall into two categories: sequencing-based methods (Visium, GeoMx, Stereo-seq) offering whole-transcriptome coverage at modest resolution and imaging-based platforms (Xenium, CosMx, MERFISH) providing single-cell or subcellular detail with targeted gene panels. These technologies reveal spatially organized immune responses, local tissue remodeling, and pathogen niches across viruses, bacteria, and parasites. In viral infection, ST uncovered heterogeneity in COVID-19 lung microenvironments, spatial immune activation in lymphoid tissues, and variant-specific inflammatory patterns. In bacterial disease, ST delineated granuloma architecture in tuberculosis and mapped vaccine-induced lung responses in Shigella studies. Parasitic infection studies identified localized inflammatory hotspots and microenvironmental control of T-cell differentiation in malaria. Despite powerful insights, ST faces constraints including RNA quality limitations, tradeoffs between resolution and transcript breadth, high cost, and analytical complexity. Nonetheless, ST increasingly informs vaccine design by identifying tissue-specific immune programs and protective microenvironments and is poised to become a standard tool for infectious disease biology. Full article