Search Results (322)

Background: Kidney transplant recipients (KTRs) exhibit a significantly diminished immune response to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccines compared with the general population, primarily due to ongoing immunosuppressive therapy. This study evaluated the immunogenicity of a third SARS-CoV-2 mRNA vaccine dose in KTRs and assessed the association between antibody response and protection against SARS-CoV-2 breakthrough infection. Additionally, the clinical and immunological correlates of post-vaccination SARS-CoV-2 infection were examined. Methods: A prospective cohort of 135 KTRs received a third vaccine dose approximately six months following the second dose. Plasma samples were collected at baseline (pre-vaccination), six months after the second dose, and six weeks following the third dose. Humoral responses were assessed using SARS-CoV-2-specific Immunoglobulin G (IgG) titers and virus neutralization assays against wild-type (WT) and viral strains, including multiple Omicron sub-lineages. Results: After the third vaccine dose, 74% of the KTRs had detectable SARS-CoV-2-specific IgG antibodies, compared with 48% following the second dose. The mean IgG titers increased approximately ten-fold post-booster. Despite this increase, neutralizing activity against the Omicron variants remained significantly lower than that against the WT strain. KTRs who subsequently experienced a SARS-CoV-2 breakthrough infection demonstrated reduced neutralizing antibody activity across all variants tested. Additionally, individuals receiving triple immunosuppressive therapy had a significantly higher risk of SARS-CoV-2 breakthrough infection compared with those on dual or monotherapy. A multivariate machine learning analysis identified age and neutralizing activity against WT, Delta, and Omicron BA.2 as the most robust correlates of SARS-CoV-2 breakthrough infection. Conclusions: A third SARS-CoV-2 mRNA vaccine dose significantly improves SARS-CoV-2-specific IgG levels in KTRs; however, the neutralizing response against Omicron variants remains suboptimal. Diminished neutralizing capacity and intensified immunosuppression are key determinants of SARS-CoV-2 breakthrough infection in this immunocompromised population. Full article

Narrative review synthesizes the most current literature on the SARS-CoV-2 XEC variant, focusing on its genomic evolution, immune evasion characteristics, epidemiological dynamics, and public health implications. To achieve this, we conducted a structured search of the literature of peer-reviewed articles, preprints, and official surveillance data from 2023 to early 2025, prioritizing virological, clinical, and immunological reports related to XEC and its parent lineages. Defined by the distinctive spike protein mutations, T22N and Q493E, XEC exhibits modest reductions in neutralization in vitro, although current evidence suggests that mRNA booster vaccines, including those targeting JN.1 and KP.2, retain cross-protective efficacy against symptomatic and severe disease. The XEC strain of SARS-CoV-2 has drawn particular attention due to its increasing prevalence in multiple regions and its potential to displace other Omicron subvariants, although direct evidence of enhanced replicative fitness is currently lacking. Preliminary analyses also indicated that glycosylation changes at the N-terminal domain enhance infectivity and immunological evasion, which is expected to underpin the increasing prevalence of XEC. The XEC variant, while still emerging, is marked by a unique recombination pattern and a set of spike protein mutations (T22N and Q493E) that collectively demonstrate increased immune evasion potential and epidemiological expansion across Europe and North America. Current evidence does not conclusively associate XEC with greater disease severity, although additional research is required to determine its clinical relevance. Key knowledge gaps include the precise role of recombination events in XEC evolution and the duration of cross-protective T-cell responses. New research priorities include genomic surveillance in undersampled regions, updated vaccine formulations against novel spike epitopes, and long-term longitudinal studies to monitor post-acute sequelae. These efforts can be augmented by computational modeling and the One Health approach, which combines human and veterinary sciences. Recent computational findings (GISAID, 2024) point to the potential of XEC for further mutations in under-surveilled reservoirs, enhancing containment challenges and risks. Addressing the potential risks associated with the XEC variant is expected to benefit from interdisciplinary coordination, particularly in regions where genomic surveillance indicates a measurable increase in prevalence. Full article

Avian metapneumovirus subtype B (aMPV/B) is an economically significant pathogen in poultry, causing respiratory and reproductive disorders. In this study, 167 clinical samples were collected from commercial poultry farms across Thailand to investigate the prevalence, genetic diversity, and evolutionary dynamics of aMPV/B. Nested RT-PCR targeting the G gene revealed a positivity rate of 34.13% (57/167). Phylogenetic and Median-joining network analyses of sequenced amplicons identified two distinct Thai lineages: one genetically similar to vaccine strains and another of unknown origin. Divergence time analysis using a Bayesian framework estimated the time to the most recent common ancestor (tMRCA) of these lineages around 2006, with further sub-lineage diversification occurring around 2009 and 2016. These findings suggest that the circulating Thai aMPV/B strains likely stem from limited introduction events followed by local evolution. Lineage-specific amino acid substitutions within the G gene were identified, which may affect antigenic properties and immune recognition. This study highlights the molecular heterogeneity and ongoing diversification of aMPV/B in Thailand and underscores the need for sustained genomic surveillance and regionally tailored vaccination strategies. Full article

Tusavirus 1 of species Protoparvovirus incertum 1 (family Parvoviridae) was first identified in humans and later in small ruminants (caprine and ovine). This study reports the full-length coding sequences (~4400–4600 nt) of three novel tusavirus-related protoparvoviruses from ovine (“misavirus”, PV540792), for the first time bovine (“sisavirus”, PV540793) and subsequently from caprine (“gisavirus” PV540850/51) fecal samples, using next-generation sequencing (NGS) and PCR techniques. Their NS1, VP1 and VP2 proteins shared 61–63% amino acid identities with each other and with tusaviruses, suggesting these three viruses belong to three novel species in the genus Protoparvovirus. Phylogenetic analyses placed them with tusaviruses on a separate main branch, implying a shared origin among these most likely ruminant protoparvoviruses. A small-scale epidemiological investigation on 318 ruminant enteric samples using novel generic NS1 primers found misavirus in 14/51 (27.5%) ovine and sisavirus in 19/203 (9.4%) bovine samples from multiple Hungarian farms. Tusavirus was present in 5/51 (9.8%) ovine and 15/62 (24.2%) caprine samples, all from one farm. The highest prevalences for all three viruses were found in animals aged 2–12 months, though sporadic cases were also found in other age groups. Partial NS and VP sequence-based phylogenetic trees showed virus-specific lineages for misa-, sisa-, gisa- and tusaviruses, with various strains forming sub-lineages. These findings suggest the presence of multiple genotypes and/or members of additional species, which was supported by a VP sequence-based hierarchical cluster analysis. The study’s viruses were mostly phylogenetically separated by host; however, two bovine sisavirus strains with diverse phylogenetic localizations in the NS (belonging to bovine sisaviruses) and VP1 trees (distantly related to ovine misaviruses) could indicate previous (interspecies?) recombination events. Full article

Background: Infections caused by carbapenem-resistant Enterobacterales have steadily multiplied over time, becoming a major threat to healthcare systems due to limited therapeutic options and high case-fatality rates. Case report: We studied a patient who, after being discharged from an ICU, developed salmonellosis caused by an antibiotic-susceptible S. enteritidis. After undergoing treatment with ciprofloxacin, the patient presented an episode of asymptomatic bacteriuria originated by a carbapenem and ciprofloxacin-resistant S. enteritidis. Results: Whole genome sequencing analysis revealed that both Salmonella isolates belonged to the same strain, and that isolate SEn_T2 acquired a plasmid carrying both bla_NDM-1 and qnrA1 genes (pIncCSEn) which was previously present in the patient’s gut in at least one Enterobacter cloacae isolate. Additionally, pIncCSEN was identified as a putatively new sub-lineage of IncC2 plasmids which lacked the first copy of the methyltransferase gene dcm and the rhs gene. The resistance genes bla_NDM-1 and qnrA1 were incorporated into a Tn21-derived transposon that included a complex class 1 integron whose genetic arrangement was: intI1- dfrA12- orfF- aadA2- qacEΔ1-sul1-ISCR1- trpF- ble- bla_NDM-1 (in reverse direction)- ISAba125-ISCR1- qnrA- cmlA1- qacEΔ1-sul1. Conclusions: Antimicrobial persistence and co-selection of antibiotic resistance play an important role in the dissemination of antimicrobial resistance genes; in this regard, a joint effort involving the infection control team, effective antibiotic stewardship, and genomic surveillance could help mitigate the spread of these multidrug resistant microorganisms. Full article

Porcine Reproductive and Respiratory Syndrome Virus 2 (PRRSV-2) represents one of the greatest threats to global pork production. Increased incidence of a genetic variant of Porcine Reproductive and Respiratory Syndrome Virus (variant 1H.18) was recently reported in the Midwestern USA Sequence comparisons in the ORF5 region indicate that 1H.18 was closely related to both sub-lineages L1H and L1C. To expand our understanding and attempt to elucidate the origin of the 1H.18, we sequenced a near-complete genome, covering all coding regions, and investigated the occurrence of recombination events that may have contributed to the emergence of the new variant. At least six distinct recombination events were identified across the coding portion of the genome. Evidence of recombination in the ORF5 region between variants 1H.31 and 1C.3 was detected. Our results suggest a likely origin of 1H.18 driven by recombination. Full article

Background: Porcine Reproductive and Respiratory Syndrome (PRRS) is a highly contagious disease characterized by reproductive failure in sows and severe respiratory disorders across all swine ages, causing significant economic losses. In China, the PRRSV epidemiological landscape is complex, with the coexistence of multiple lineages and frequent recombination. The major circulating strains include sublineages 1.8 (NADC30-like PRRSV) and 1.5 (NADC34-like PRRSV), along with lineages 8 (HP-like PRRSV) and 5 (VR2332-like PRRSV), highlighting the urgent need for rapid detection and lineage differentiation. Methods: A quadruplex RT-qPCR assay was developed targeting lineage-specific deletions in the NSP2 gene to simultaneously detect PRRSV-2 and differentiate NADC30-like PRRSV, HP-like PRRSV, and NADC34-like PRRSV strains. The assay was optimized with respect to reaction conditions, including annealing temperature, primers, and probe concentrations. The method’s performance was evaluated in terms of specificity, sensitivity, repeatability, stability, limit of detection (LOD), and consistency with sequencing results. Results: The assay demonstrated high sensitivity (LOD of 3 copies/μL), high specificity, and good repeatability (coefficient of variation < 1.5%). Field application using 938 samples from Guangxi A and B farms revealed NADC30-like PRRSV wild-type strains at positivity rates of 13.44% and 3.53%, respectively. Positive samples selected for sequencing were further confirmed using ORF5-based phylogenetic analysis and NSP2 deletion pattern comparison, which aligned with RT-qPCR detection results. Field application primarily detected NADC30-like PRRSV, while further validation is still needed for HP-like and NADC34-like strains. The developed quadruplex RT-qPCR assay enables rapid and simultaneous detection of PRRSV-2 and differentiation of three major lineages, providing a sensitive, specific, and reliable tool for distinguishing vaccine-derived from circulating strains and supporting targeted disease surveillance and control in swine farms. Full article

Tuberculosis remains a significant health issue in Mexico, which has one of the highest incidence rates in the Americas. This study aimed to analyze the circulating sublineages, spoligotypes, drug resistance, and transmission patterns of Mycobacterium tuberculosis in Mexico’s Central Western region using whole-genome sequencing. Seventy-seven Mycobacterium tuberculosis strains underwent phenotypic drug susceptibility testing via MGIT. Genotypic resistance was assessed with TB-Profiler and Mykrobe, while phylogenetic relationships were reconstructed using Snippy and RaxML. SpoTyping identified circulating SITs and families, with a 5-SNP threshold defining genomic transmission clusters. The predominant sublineages were 4.1.1.3 (X-type, n = 19) and 4.1.2.1 (LAM, n = 11), with rare sublineages (EAI5, EAI2-Manila, and Beijing) also observed. Resistance to at least one first-line drug was found in 63.3% of strains, with streptomycin mono-resistance (24.5%) being notable. Multidrug-resistant TB was identified in 16.3% (n = 8) of strains. Five genomic clusters, involving 18.7% of strains, were identified. This study highlights the sublineage diversity in Mexico, emphasizing its importance in global databases and resistance research. The findings, such as SIT47 in GC1, underscore the value of localized genomic studies for effective TB control. Full article

Due to its high genomic variability, the epidemiological landscape of porcine reproductive and respiratory syndrome virus (PRRSV) has become increasingly complex in recent years. From 2022 to 2023, we collected a total of 1044 clinical samples from pigs suspected of PRRSV infection in China and discovered a PRRSV-positive rate of 29.8% (311/1044) using RT-PCR targeting the nsp2 gene. Among these positive samples, NADC30/34-like PRRSV, highly pathogenic PRRSV (HP-PRRSV), and classical PRRSV strains accounted for 60.1%, 37.9%, and 4.5%, respectively. These results indicate that the most prevalent PRRSV strains in China are NADC30/34-like PRRSV, followed by HP-PRRSV. Two PRRSV strains, JX03 and HN08, were isolated, and TCID₅₀ assays were performed to determine their titers at different time points post-infection, revealing differences in their proliferation kinetics. Phylogenetic, amino acid sequence, and recombination analyses demonstrated that the JX03 and HN08 strains cluster within lineage 8 (HP-PRRSV) and sublineage 1.5 (NADC34-like PRRSV), respectively. Notably, the HN08 strain was identified as a recombinant between the NADC30-like and NADC34-like strains, while no recombination event was detected in the JX03 strain. Pathogenicity assessments showed that the JX03 strain exhibited higher pathogenicity than the CHN-HB-2018 strain (a NADC30-like PRRSV strain was previously isolated by our lab), as evidenced by differences in clinical signs and mortality rates in piglets. In contrast, HN08 displayed no obvious clinical symptoms or mortality, revealing lower pathogenicity than the CHN-HB-2018 strain. These findings provide valuable information on the epidemiological and genetic characteristics of PRRSV strains in China, laying a foundation for the development of effective strategies against PRRSV. Full article

(1) Background: The currently circulating variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits resistance to antibodies induced by vaccines. The World Health Organization recommended the use of monovalent XBB.1 sublineages (e.g., XBB.1.5) as an antigenic component in 2023. (2) Objective: In this study, we aimed to develop vaccines based on the XBB.1.5 receptor-binding domain (RBD) to combat the recently emerged SARS-CoV-2 XBB and JN.1 variants, as well as previously circulating variants. (3) Methods: Glycoengineered Pichia pastoris was utilized to produce a recombinant XBB.1.5 RBD protein with mammalian-like and fucose-free N-glycosylation. The XBB.1.5 RBD was mixed with Al(OH)₃:CpG adjuvants to prepare monovalent vaccines. Thereafter, the XBB.1.5 RBD was mixed with the Beta (B.1.351), Delta (B.1.617.2), or Omicron (BA.2) RBDs (1:1 ratio), along with Al(OH)₃:CpG, to prepare bivalent vaccines. BALB/c mice were immunized with the monovalent and bivalent vaccines. Neutralizing antibody titers were assessed via pseudovirus and authentic virus assays; humoral immune responses were analyzed by RBD-binding IgG subtypes. (4) Results: The monovalent vaccine induced higher neutralizing antibody titers against Delta, BA.2, XBB.1.5, and JN.1 compared to those in mice immunized solely with Al(OH)₃:CpG, as demonstrated by pseudovirus virus assays. The XBB.1.5/Delta RBD and XBB.1.5/Beta RBD-based bivalent vaccines provided potent protection against the BA.2, XBB.1.5, JN.1, and KP.2 variants, as well as the previously circulating Delta and Beta variants. All monovalent and bivalent vaccines induced high levels of RBD-binding IgG (IgG1, IgG2a, IgG2b, and IgG3) antibodies in mice, suggesting that they elicited robust humoral immune responses. The serum samples from mice immunized with the XBB.1.5 RBD-based and XBB.1.5/Delta RBD-based vaccines could neutralize the authentic XBB.1.16 virus. (5) Conclusions: The XBB.1.5/Beta and XBB.1.5/Delta RBD-based bivalent vaccines are considered as potential candidates for broad-spectrum vaccines against SARS-CoV-2 variants. Full article

Sargassum hemiphyllum var. chinense is a common brown seaweed along the southeastern coast of China, playing a significant ecological role and possessing considerable resource utilization value. However, its genetic diversity and phylogeographic patterns remain poorly understood. In this study, we employed multiple molecular markers, including the nuclear ITS sequence (ribosomal internal transcribed spacer), the plastid rbcL gene (encoding the large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase), and the mitochondrial cox3 and cox1 genes (encoding cytochrome c oxidase subunits III and I, respectively), to elucidate the genetic and phylogeographic structure of S. hemiphyllum var. chinense. Our findings demonstrate that the combined use of plastid and mitochondrial gene sequences is suitable for phylogeographic studies of this species. Genetic structure difference was observed among 15 populations which localities covering most of its distribution range, likely resulting from colonization by ancestors of different origins and limited gene flow among populations. The study revealed two distinct lineages of S. hemiphyllum var. chinense, exhibiting a north–south geographical distribution with a mixed zone in the southern Fujian–eastern Guangdong coastal region. These lineages are inferred to have diverged during the Middle to Late Pleistocene due to the isolation of the East China Sea and South China Sea during glacial periods. Sub-lineage differentiation was also detected within the northern lineage. The southern lineage experienced demographic expansion following the end of the Last Glacial Maximum, while the northern lineage remained stable. The southern Fujian–eastern Guangdong region, characterized by high genetic diversity, may have served as a glacial refugium or a contact zone for the post-glacial recolonization of the two lineages. Global warming may lead to range contraction and reduced genetic diversity in this species. The high genetic diversity area should be prioritized for conservation efforts. Overall, these findings provide insights into the genetic structure status and causes of S. hemiphyllum var. chinense and offer a scientific basis for proposing reasonable measures for its resource management. Full article

Vaccination has been instrumental in curbing the transmission of SARS-CoV-2 and mitigating the severity of clinical manifestations associated with COVID-19. Numerous COVID-19 vaccines have been developed to this effect, including BioNTech-Pfizer and Moderna’s mRNA vaccines, as well as adenovirus vector-based vaccines such as Oxford–AstraZeneca. However, the emergence of new variants and subvariants of SARS-CoV-2, characterized by enhanced transmissibility and immune evasion, poses significant challenges to the efficacy of current vaccination strategies. In this review, we aim to comprehensively outline the landscape of emerging SARS-CoV-2 variants of concern (VOCs) and sub-lineages that have recently surfaced in the post-pandemic years. We assess the effectiveness of existing vaccines, including their booster doses, against these emerging variants and subvariants, such as BA.2-derived sub-lineages, XBB sub-lineages, and BA.2.86 (Pirola). Furthermore, we discuss the latest advancements in vaccine technology, including multivalent and pan-coronavirus approaches, along with the development of several next-generation coronavirus vaccines, such as exosome-based, virus-like particle (VLP), mucosal, and nanomaterial-based vaccines. Finally, we highlight the key challenges and critical areas for future research to address the evolving threat of SARS-CoV-2 subvariants and to develop strategies for combating the emergence of new viral threats, thereby improving preparedness for future pandemics. Full article

The new Nuvaxovid protein-based and Pfizer-BioNTech mRNA-based vaccines targeting Omicron XBB.1.5 were available during the 2023–2024 autumn/winter vaccination campaign for frail individuals, including people with HIV (PWH). We assessed the immune response in 51 PWH on stable ART who received a booster with either the Nuvaxovid protein-based (n = 25) or Pfizer-BioNTech mRNA-based XBB.1.5 vaccine (n = 26). The median age was 57 years (IQR 51–65), the median count of CD4 at T0 was 652/mmc (503–935), and CD4 nadir was 226/mmc (95–340). Samples were collected before (T0) and one month after (T1) the booster. We measured neutralizing antibodies (nAbs) titers against D614G, XBB.1.6, and JN.1 variants and T-cell IFN-γ levels produced upon specific stimulation. Regardless of the vaccine used, we observed a marked increase in nAbs titers from T0 to T1 against all the subvariants, but no evidence for a change in IFN-γ release. After controlling for confounders, there was no evidence for a difference in the T0-T1 change in nAbs titers against XBB.1.16 and JN.1 by the type of vaccine, while Nuvaxovid determined a smaller increase in D614G nAbs (p = 0.008). The XBB.1.5 protein-based vaccine’s immunogenicity as a fifth or later booster was comparable to the Pfizer-BioNTech mRNA vaccine, particularly against recent Omicron variants. Full article

Background: The SARS-CoV-2 variants KP.3.1.1 and XEC currently dominate the COVID-19 epidemic. However, their cell tropism, proteolytic processing, and susceptibility to neutralization by monoclonal antibodies remain incompletely characterized. Methods: We employed pseudotyped viruses to assess the entry efficiency of KP.3.1.1 and XEC in various cell lines, their dependence on TMPRSS2 for lung cell entry, and their ability to use ACE2 for infection. Additionally, we evaluated their susceptibility to neutralization by monoclonal antibodies BD55-4637 and BD55-5514. Results: KP.3.1.1 and XEC entered cell lines with similar efficiency as the parental JN.1 lineage and utilized TMPRSS2 for Calu-3 lung cell entry. Unlike JN.1, KP.3.1.1 and XEC failed to efficiently use murine ACE2 for cell entry. Both variants were effectively neutralized by the monoclonal antibodies BD55-4637 and BD55-5514, suggesting therapeutic potential. Conclusions: Our findings demonstrate that JN.1, KP.3.1.1, and XEC, like their predecessor BA.2.86, rely on TMPRSS2 for lung cell entry and remain sensitive to certain neutralizing monoclonal antibodies. However, these variants differ in their ability to utilize ACE2 species orthologs for cell entry. Full article

Mutation is one of the most important drivers of viral evolution and genome variability, allowing viruses to potentially evade host immune responses and develop drug resistance. In the context of COVID-19, local genomic surveillance of circulating virus populations is therefore critical. The goals of this study were to describe the distribution of different SARS-CoV-2 lineages, assess their genomic differences, and infer virus importation events in Bangladesh. We individually aligned 1965 SARS-CoV-2 genome sequences obtained between April 2020 and June 2021 to the Wuhan-1 sequence and used the resulting multiple sequence alignment as input to infer a maximum likelihood phylogenetic tree. Sequences were assigned to lineages as described by the hierarchical Pangolin nomenclature scheme. We built a phylogeographic model using the virus population genome sequence variation to infer the number of virus importation events. We observed thirty-four lineages and sub-lineages in Bangladesh, with B.1.1.25 and its sub-lineages D.* (979 sequences) dominating, as well as the Beta variant of concern (VOC) B.1.351 and its sub-lineages B.1.351.* (403 sequences). The earliest B.1.1.25/D.* lineages likely resulted from multiple introductions, some of which led to larger outbreak clusters. There were 570 missense mutations, 426 synonymous mutations, 18 frameshift mutations, 7 deletions, 2 insertions, 10 changes at start/stop codons, and 64 mutations in intergenic or untranslated regions. According to phylogeographic modeling, there were 31 importation events into Bangladesh (95% CI: 27–36). Like elsewhere, Bangladesh has experienced distinct waves of dominant lineages during the COVID-19 pandemic; this study focuses on the emergence and displacement of the first wave-dominated lineage, which contains mutations seen in several VOCs and may have had a transmission advantage over the extant lineages. Full article