IntroductionSARS-CoV-2 has been deprioritized post-pandemic, especially in Africa. Vaccination in Kenya was conducted using the Wuhan-based vaccines only, which showed reduced neutralization efficacy against Omicron and its sublineages.MethodsWe performed SARS-CoV-2 immune surveillance in five health facilities within the Kilifi Health Demographic and Surveillance System from November 2024 to March 2026. Patients in the facilities presenting acute respiratory symptoms were recruited and nasopharyngeal/oropharyngeal swabs taken for SARS-CoV-2 RT-PCR. Convalescent plasma from 30 patients with confirmed SARS-CoV-2 RT-PCR positive tests and genome sequences were taken for sero-neutralization assays against the infecting variants LF.7, MV.1, and globally predominant strains, XEC.4, LP.8.1 and XFG.ResultsIn total 5115 patients were tested and 171 patients (3.4%) were positive for SARS-CoV-2. Cough (91.7%), nasal discharge (74.5%) and fever (55.4%) were the most common symptoms while wheezing (2%) and crackles (2.8%) were rarest. Sequencing revealed circulation of JN.1 omicron sub-lineages, LF.7, MV.1 and XEF. Sera from majority of individuals infected by the dominant variants, LF.7 and MV.1 were able to neutralize infecting variants but not the recently circulating XFG variant 23% (7/30) suggesting that infection with a JN.1 lineage virus alone is not sufficient to prevent re-infection with XFG. Overlapping titer distributions was observed between vaccinated and unvaccinated sera, with no statistically significant difference observed for any variant.ConclusionOur study demonstrates that SARS-CoV-2 continues to circulate in coastal Kenya causing predominantly mild upper respiratory illness while evolution enabling immune escape. These findings emphasize the importance of integrated genomic and immunological surveillance to track emerging variants, evaluate population-level protection, and inform future vaccine update strategies and public health preparedness efforts.
Identifying viruses with zoonotic potential on the basis of their ability to enter human cells is a critical component of pandemic prediction, prevention and preparedness. Here using a computational approach that retains maximum phylogenetic diversity, we selected an optimal subset of alphacoronavirus spike proteins to screen against broad coronavirus receptor libraries. Most of the selected spike proteins did not use any of the established coronavirus receptors. However, the pseudotyped spike protein of Cardioderma cor (heart-nosed bat) coronavirus KY43 (CcCoV-KY43) could enter human cells. Using a recombinant CcCoV receptor-binding domain (RBD) and a human receptor screening platform, we identified direct interactions with the human CEACAM proteins CEACAM3, CEACAM5 and CEACAM6. Overexpression of human CEACAM6—a protein widely expressed in the human lung—conferred permissivity to otherwise refractory human cells. A crystal structure showed that the RBD binds the amino-terminal IgV-like domain of human CEACAM6. Immune surveillance studies using sera of individuals from the Taveta region of Kenya, where CcCoV-KY43 was identified, did not show significant evidence of recent spillover. Wider characterization of alphacoronaviruses related to CcCoV-KY43 showed that human CEACAM6 is used by two other CcCoVs collected in Kenya. Moreover, there was more restricted nonhuman CEACAM6 tropism for viruses isolated from Rhinolophus bats from Russia and China. Thus, alphacoronaviruses that use CEACAM6 are probably geographically widespread, and viruses from East Africa show potential for transmission to humans.
Sarbecoviruses interact with their receptor, angiotensin converting enzyme 2 (ACE2), via the receptor binding domain (RBD) of Spike, the immunodominant target for neutralising antibodies. Understanding the interplay and correlation between ACE2-determined host range and antigenicity is vitally important for understanding the zoonotic potential of related bat sarbecoviruses. Using binding assays, pseudotype-entry assays and a diverse panel of mammalian ACE2 proteins, we examined the host range and related antigenicity of multiple bat coronaviruses. Broad bat ACE2 usage (a generalist phenotype) was most common in clade 1 sarbecoviruses, including SARS-CoV-2 and the BANAL isolates from Laos. In contrast, clade 3 (e.g., RhGB07) and 5 (e.g., Rc-o319) sarbecoviruses exhibited more restricted ACE2 usage (a specialist phenotype). A novel structure for RhGB07 Spike further helped to identify RBD residues associated with this receptor specialism. Interestingly, the generalist phenotypes were largely maintained with more diverse mammalian receptor libraries, including human, non-human primate, livestock, rodent ACE2 and potential intermediate reservoir hosts (e.g., civet, racoon dog, pangolin), while specialists, like RhGB07, exhibited wider phenotypic diversity. The impact of SARS-CoV-2’s continued evolution in humans was also examined, identifying an expanding and/or shifting pattern of generalism for variants, especially Omicron and its sub-lineages. Furthermore, we compared and correlated these entry phenotypes with antigenicity using sera from SARS-CoV-2 convalescent individuals. Clade 1 viruses, phylogenetically related to SARS-CoV-2, were antigenically the most similar, with robust evidence for cross-neutralisation; however, there was still evidence for limited cross-neutralisation across the entire sub-genus. Finally, using monoclonal antibodies, derived from COVID-19 vaccinees with breakthrough infections, we pin-pointed the antibody epitope classes responsible for wider neutralisation. Our research indicates that generalist ACE2-using sarbecoviruses are phylogenetically and antigenically related to SARS-CoV-2. ### Competing Interest Statement The authors have declared no competing interest.
Chalcones, a naturally occurring class of molecules found in various plants, serve as both precursors and final products in the biosynthesis of flavonoids. Renowned for their diverse therapeutic actions, chalcones demonstrate anti-inflammatory, anti-tumoral, antimalarial and antiviral activities. The structure of chalcones allows chemical manipulation, making them attractive for metal coordination, such as with copper, an essential metal for living organisms. Here, we characterize the activity of CuL2phen and CuL1phen against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in which L1 and L2 are two forms of the chalcones 3-(4-(benzyloxy)phenyl)-1-(4-fluoro-2-hydroxyphenyl)prop-2-en-1-one and 3-(4-(benzyloxy)phenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one, respectively, and phen is phenanthroline. CuL1phen and CuL2phen anti-SARS-CoV-2 activity were studied in the viral replication cycle employing both the SARS-CoV-2-NeonGreen infectious clone and wild-type isolates. The SI of CuL1phen and CuL2phen was found to be 1.7 and 5.5, respectively, demonstrating that CuL2phen is a more promising compound. CuL2phen impaired SARS-CoV-2 entry, predicted by molecular docking calculations to disrupt the glycoprotein S and angiotensin-converting enzyme 2 (ACE2) binding, emphasized by the low EC50 in pseudotyped virus entry assay. Further, CuL2phen was identified as SARS-CoV-2 post-entry inhibitor, probably due to its strong interaction with SARS-CoV-2 double stranded RNA. Altogether, the data suggest that CuL2phen acts by impairing SARS-CoV-2 entry by disrupting the viral envelope as well as interrupting RNA replication through specifically intercalating into the dsRNA. The obtained results give us mechanistic insights into the activity of this promising Cu(II) metallodrug candidate in SARS-CoV-2 infection.
Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus with epidemic potential. Despite the threat NiV poses, no therapeutics are licensed to treat infection. Studies have shown that monoclonal antibodies (mAb) can protect animals against NiV and the related Hendra virus (HeV). The best studied mAb, m102.4, has been used to treat infected patients on a compassionate basis, and has entered clinical trials. However, there is a need to define additional mAbs with therapeutic potential, which could be combined with m102.4 to improve neutralising potency and breadth. Here, we isolated five high affinity mAbs from a pig vaccinated with mRNA encoding the NiV G glycoprotein, which bound the recombinant NiV Malaysia strain (NiV-M) G, and one of which (mAb A2) also cross-reacted with HeV G. All mAbs neutralised NiV-M pseudovirus but only mAb A2 neutralised pseudovirus representing the NiV Bangladesh (NiV-B) strain. mAb A2 and the most potent NiV-M neutralising mAb, C1, showed minimal competition with each other and m102.4, suggesting recognition of non-overlapping epitopes. Single-particle cryogenic electron microscopy of the NiV-M G receptor binding domain complexed to A1 and C2 Fab fragments revealed distinct epitopes that did not overlap with the receptor-binding site, targeted by m102.4, suggesting action through steric impedance of receptor binding or interference downstream of receptor engagement. Administration of mAb A2 to hamsters did not provide complete protection against NiV-B challenge (60% survival), however, a split dose of mAb A2 and m102.4 provided the same protection as m102.4 alone (100% survival). Collectively, these data demonstrate the potential of the porcine model for isolation of therapeutic candidate mAbs, which contribute both to our understanding of the NiV G antigenic landscape, and the development of mAb combinations, that exert complementary mechanisms of neutralisation, for therapeutic intervention.
In this study, the phenotypic consequences of naturally occurring single nucleotide polymorphisms (SNPs) in the Middle East respiratory syndrome coronavirus (MERS-CoV) Spike protein were investigated. The impact of Spike mutations on the syncytia formation and neutralisation of contemporary MERS-CoV strains is not currently well understood. Mutations were identified by aligning 584 MERS-CoV Spike sequences from either human clinical isolates collected between 2012 and 2024 or from a clinical isolate that had been passaged in human cells. Fifteen SNPs of interest occurring in the N-terminal domain (NTD), receptor binding domain (RBD) and adjacent to the S1/S2 cleavage site were selected for further characterisation based on their location in the Spike protein, frequency and identification in previous studies. A contemporary clade B, lineage 5 wildtype Spike sequence, obtained from a human MERS-CoV clinical isolate, was used as the backbone in this study. The mutations of interest were introduced to the wildtype backbone to generate Spike variants. Spike variants were characterised via cell-cell fusion assays, and a lentiviral pseudotyping system was used to investigate the impact of these Spike mutations on neutralisation. The I529T, E536K and L745F mutations were shown to increase fusion and syncytia formation. The L411F, T424I, L506F, L745F and T746K mutations were found to increase resistance to neutralisation by pooled patient sera. This study has identified novel naturally occurring Spike mutations that resulted in phenotypic differences in the syncytia formation and neutralisation of contemporary MERS-CoV strains. Continued investigation of the phenotypic consequences of MERS-CoV Spike mutations is essential for assessing the risk to public health, especially given the pandemic potential of this virus.
BACKGROUND:Seasonal influenza causes significant morbidity and mortality annually. In 2025, the genetically divergent A/H3N2 K subclade (J.2.4.1) emerged with substantial haemagglutinin mutations. However, despite suggested antigenic escape, UK vaccine effectiveness estimates and epidemiological data demonstrated a relatively normal influenza season across 2025-26. We examined neutralising antibody responses in human cohorts to investigate existing and vaccine-induced immunity to K clade viruses. METHODS:We characterised the antigenic relationships of a selection of A/H3N2 viruses spanning recent evolution including a subclade K virus using antigenic cartography, followed by serological antibody profiling of four human cohorts from the United Kingdom and Norway using microneutralisation (MN) and haemagglutination inhibition (HAI) assays. FINDINGS:Antigenic cartography from single-infection ferret antisera suggests significant antigenic drift from the vaccine strains. MN and HAI titres from 243 individuals across 4 human cohorts (ages 1-105 years) were measured for comparison. The 2025/26 Northern Hemisphere seasonal inactivated egg-derived trivalent influenza vaccine (eTIV, with J.2 A/H3N2) significantly boosted MN and HAI titres against all A/H3N2 viruses tested, including a subclade K virus (p < 0.001). Furthermore, serological profiles of cohorts stratified by age groups (≤5, >5-≤15, >20-≤25, >25-<60, and ≥60) showed pre-existing reactivity against the emergent subclade K viruses, with minimal inter-age variation, suggesting there was not an immunity gap within particular age groups. INTERPRETATION:The 2025/26 seasonal inactivated eTIV vaccine effectively boosted neutralising titres despite substantial genetic and antigenic drift. Human serological profiling should be included in risk assessments and continued surveillance. FUNDING:The Francis Crick Institute with core funding from Cancer Research UK, UK Medical Research Council, and Wellcome Trust; UK Research and Innovation and UK Medical Research Council; National Institute for Health Research University College London Hospitals Biomedical Research Centre; UK Health Security Agency; Norwegian Institute of Public Health.
Bats are reservoir hosts for a number of coronaviruses, some of which may pose spillover risks for humans and other animals. We detected two alphacoronaviruses in big brown bats (Eptesicus fuscus) and little brown myotis (Myotis lucifugus) in Ontario, Canada. These viruses are closely related to other coronaviruses circulating in bats in North America and also distantly related to human and swine coronaviruses. We found high similarity in the receptor-binding domain (RBD) in viruses derived from the same species of bat, but markedly lower in those derived from other species. We also functionally characterized the accessory protein ORF3 finding that ORF3 inhibited both IFN beta production and signaling. Our study provides insights into coronavirus diversity in bats in a previously under-sampled region. This work provides a baseline for in-depth surveillance to characterize the transmission dynamics of endemic coronaviruses in free-ranging wildlife, and for exploring the evolutionary relationships between coronaviruses and their hosts.
Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic henipaviruses without approved human vaccines or therapies. Here, we report on a highly potent bispecific therapeutic that combines an anti-fusion (F) nanobody with an anti-receptor binding protein (RBP) antibody to deliver a dual-targeting biologic that is resistant to viral escape. We show that the nanobody, DS90, engages a unique, conserved site within prefusion F of NiV and HeV, and provides neutralization and complete protection from NiV disease. Bispecific engineering of DS90 with the anti-RBP mAb m102.4 results in neutralization, elimination of viral escape and superior protection from NiV disease compared to leading monovalent approaches. These findings carry implications for the development of cross-neutralizing immunotherapies that limit the emergence of henipaviral escape mutants. ### Competing Interest Statement The authors have declared no competing interest.
In infected individuals, viruses are present as a population consisting of dominant and minor variant genomes. Most databases contain information on the dominant genome sequence. Since the emergence of SARS-CoV-2 in late 2019, variants have been selected that are more transmissible and capable of partial immune escape. Currently, models for projecting the evolution of SARS-CoV-2 are based on using dominant genome sequences to forecast whether a known mutation will be prevalent in the future. However, novel variants of SARS-CoV-2 (and other viruses) are driven by evolutionary pressure acting on minor variant genomes, which then become dominant and form a potential next wave of infection. In this study, sequencing data from 96 209 patients, sampled over a 3-year period, were used to analyse patterns of minor variant genomes. These data were used to develop unsupervised machine learning clusters to identify amino acids that had a greater potential for mutation than others in the Spike protein. Being able to identify amino acids that may be present in future variants would better inform the design of longer-lived medical countermeasures and allow a risk-based evaluation of viral properties, including assessment of transmissibility and immune escape, thus providing candidates with early warning signals for when a new variant of SARS-CoV-2 emerges.
IntroductionNipah virus (NiV) is one of a group of highly pathogenic viruses classified within the Henipavirus genus. Since 2012 at least 11 new henipa-like viruses have been identified, including from new locations and reservoir hosts; the pathogenicity of these new viruses has yet to be determined, but two of them have been associated with morbidity, including fatalities.MethodsThe efficacy and cross-reactivity of two vaccine candidates derived from the soluble glycoproteins of both NiV and Hendra virus (HeV) was evaluated in our recently established hamster model.ResultsBoth vaccine preparations resulted in strong humoral responses against NiV antigenic targets, demonstrating cross-reactive immunity. Efficacy was determined through challenge of hamsters with NiV Malaysian (NiV-M) strain. 100% of the hamsters survived a lethal challenge dose after prime/boost immunisation with glycoproteins derived from both NiV and HeV in the presence of adjuvant, with clinical signs and pathology being significantly reduced in immunised animals.DiscussionThis is first time the NiV and HeV soluble glycoproteins have been compared in the NiV-M hamster challenge model in the presence of Alhydrogel and AddaVax, providing evidence that glycoproteins from closely related henipavirus species can provide cross-protectivity against infection from alternate henipaviruses, supporting the potential of an effective pan-henipavirus vaccine for use in a frontline outbreak response.
The continuing evolution of SARS-CoV-2 variants of concern, and the increasing spillover potential of sarbecoviruses into the human population presents an important and urgent need to discover cross-reactive monoclonal antibodies (mAbs) for future therapeutic use and identify conserved neutralising epitopes that can be used for rationale design of broadly protective sarbecovirus vaccines. Here we study the neutralising epitopes on WIV-1 Spike of three mAbs that confer broad sarbecovirues and SARS-CoV-2 variant neutralisation, including XEC and JN.1. mAb V1WT\_06 binds a highly conserved RBD site V epitope that is mediated by the heavy chain alone. V1WT\_06 contact residues are highly conserved in circulating viruses suggesting that the epitope is evolutionarily and functionally constrained. mAbs V1WT\_41 and VA14\_26 bind overlapping RBD class 4 epitopes with differing angles of approach that impact on the degree of ACE2 competition. We show that neutralisation by these mAbs is maintained when virus entry is via Japanese horseshoe bat and Halcyon horseshoe bat ACE2. These mAbs are ideal candidates for therapeutic antibody development and inform the rational design of pan-coronavirus vaccines. ### Competing Interest Statement The authors have declared no competing interest. Medical Research Council, https://ror.org/03x94j517, [MR/W005611/1], [MR/X009041/1], [MR/Y004205/1], CC2058 Wellcome Trust, [226141/Z/22/Z], CC2058 Gates Foundation, OPP1192002, OPP1215550, INV-035610
Nipah virus (NiV) and Hendra virus (HeV) are highly pathogenic henipaviruses without approved human vaccines or therapies. Here, we report on a highly potent bispecific therapeutic that combines an anti-fusion glycoprotein nanobody with an anti-receptor-binding glycoprotein (RBP) antibody to deliver a dual-targeting biologic that is resistant to viral escape. We show that the nanobody, DS90, engages a unique, conserved site within the fusion glycoprotein of NiV and HeV and provides neutralization and complete protection from NiV disease. Bispecific engineering of DS90 with the anti-RBP monoclonal antibody m102.4 results in neutralization, elimination of viral escape and superior protection from NiV disease compared to leading monovalent approaches. These findings carry implications for the development of cross-neutralizing immunotherapies that limit the emergence of henipaviral escape mutants.
BACKGROUND:As the COVID-19 pandemic has ended, the global focus has shifted from "pandemic response" to "long-term management". With no ongoing nationwide serosurveillance studies, our understanding of the level of immunity in the general population has diminished. In this study, we screened random samples from a biorepository serving the largest health board in Scotland for antibodies against SARS-CoV-2 to define the current immunological landscape, informing vaccine strategies going forward. METHODS:997 pseudonymized serum samples were obtained from NHS Greater Glasgow and Clyde (NHS GGC) biorepository in May 2024, along with associated data for age, sex, and COVID-19 vaccine history. Samples spanned ages from 19 to 98 years, with 59.0% female and 41.0% male, and 39.1% from primary healthcare (GP practices) and 61.0% from secondary healthcare (hospitals). Anti-SARS-CoV-2 receptor binding domain (RBD)-specific antibodies were measured by enzyme-linked immunosorbent assay (ELISA), while neutralising antibodies were quantified using HIV(SARS-CoV-2) pseudotype-based virus neutralisation assay (PVNA). ELISAs measured both total IgG and IgG4-mediated responses. Pseudotypes were prepared bearing spike proteins from vaccine antigens B.1 and XBB.1.5, contemporaneous circulating variants KP.3.1.1 and LB.1, and the emerging variant XEC. Samples were grouped by number of COVID-19 vaccine doses received (from no vaccination to ≥8 doses) and 12 samples from each group were screened by ELISA and PVNA. FINDINGS:The random selection of 1000 samples provided a broad cross-section of the population derived from patients with a range of individual vaccine histories, from those having received no COVID-19 vaccines to those having received 8 or more doses. The number of doses received increased with age, from a mean age of ∼40 for those having received one dose to a mean age of 77-78 for those having received 7 or 8 doses. While total IgG responses were similar across each of the groups, irrespective of vaccine history, repeated exposure to mRNA-based vaccines elicited an increase in SARS-CoV-2-specific IgG4. Neutralising antibody titres against the vaccine antigens B.1 and XBB.1.5 increased with age, reaching maximum geometric mean titres of 5610 (95% CI, 2773-11,349) for B.1 and 4577 (1832-11,440) for XBB.1.5 in those receiving 8 doses. In all groups, titres measured against the KP.3.1.1, LB.1 and XEC were significantly lower, consistent with the emergence of immune evasive variants over time. Cross-neutralisation of KP.3.1.1 was limited to maxima of 145 (62.2-336) and 187 (83.8-418) in the 7 and 8 dose groups, while titres against XEC were 105 (47-233) and 90.9 (48.1-172) respectively. INTERPRETATION:In the absence of systematic COVID-19 serosurveillance, random sampling of sera from biorepositories associated with major health boards can generate valuable data about the level of immunity in the general population, informing estimates of vaccine effectiveness and antigen selection. FUNDING:United Kingdom Medical Research Council and Genotype-to-Phenotype National Virology Consortium.
Nipah virus (NiV) causes a severe neurological disease in humans. The first NiV outbreak, in Malaysia, involved pig-to-human transmission, that resulted in significant economic losses to the local pig industry. Despite the risk NiV poses to pig-dense regions, no licensed vaccines exist. This study therefore assessed three NiV vaccine candidates in pigs: (1) adjuvanted soluble NiV (s)G protein, (2) adjuvanted pre-fusion stabilised NiV (mcs)F protein, and (3) adenoviral vectored NiV G (ChAdOx1 NiV G). NiV sG induced the strongest neutralising antibody response, NiV mcsF induced antibodies best able to neutralise cell-cell fusion, whereas ChAdOx1 NiV G elicited CD8+ T-cell responses. Despite differences in immunogenicity, prime-boost immunisation with all candidates conferred a high degree of protection against NiV infection. Follow-up studies demonstrated longevity of immune responses and broadly comparable immune responses in Bangladeshi pigs under field conditions. These studies provide a platform for developing a NiV vaccine for pigs.
Aminopeptidase N (APN) is a transmembrane protein that mediates the attachment of the spike protein of several clinically important coronaviruses (CoVs) responsible for respiratory and intestinal diseases in animals and humans. To assess the potential for APN-mediated viral tropism, we characterized APN receptor distribution in the respiratory and intestinal tissues of various artiodactyls (cervids, bovids, camelids and suids) and carnivores (canids, felids, mustelids and phocids) using immunohistochemistry. In the lungs, APN expression was limited to artiodactyls, with strong expression in the bronchiolar epithelium and weaker expression in pneumocytes. Nasal turbinate and tracheal samples, where available, showed stronger APN expression in artiodactyls over carnivores. APN was consistently detected on the microvilli of enterocytes in the small intestine across multiple taxa, while the presence in the colon was more variable. Of the animals examined, pig and alpaca consistently expressed the most abundant APN in the upper and lower respiratory tract. In silico evaluation of APN orthologue sequences from humans, artiodactyls and carnivores identified distinct evolutionary relationships. Further in silico binding predictions for alpaca alphacoronavirus and human coronavirus 229E with cognate and heterologous alpaca and human APN revealed substantial overlapping binding footprints with high conservation of amino acid residues, suggesting an evolutionary divergence and subsequent adaptation of a 229E-like or ancestral virus within a non-human animal host. This combined anatomical and in silico approach enhances understanding of host susceptibility, tissue tropism and viral transmission mechanisms in APN-dependent CoVs and has the potential to inform future strategies for disease modelling, surveillance and control.
The capacity for viruses to spillover from one host to another is dependent on their ability to bind to and enter cells from a new host. Using a computational approach that maximises phylogenetic diversity, we selected an optimal subset of 40 alphacoronavirus spike proteins, including the two human viruses NL63 and 229E, and characterised their host-range using broad mammalian APN and ACE2 receptor libraries. Based on this data, we were able to determine molecular genotypes that contribute to receptor tropism and identify alphacoronaviruses with broad (generalist) or restricted (specialist) receptor usage. Strikingly, we observed that generalism and specialism can vary significantly between closely related viruses. Using structural information, we identified key residues that determine the bat tropism of 229E-like viruses, as well as residues in the ACE2 receptor that likely restrict NL63 infection of certain mammals. Furthermore, we observed that the host range of certain bat alphacoronaviruses is expanded by TMPRSS2 priming of spike. All APN- and ACE2-using alphaCoVs in our study interacted with the receptor of at least one animal species within ecological proximity to humans, suggesting new routes for spillover. However, most bat alphacoronaviruses did not use any of receptors in our screen, refining our understanding of coronavirus entry. We propose a new approach to investigating receptor usage for viral orders/families/genera, which is not constrained by focused analysis of a limited number of sequences from human-tropic viruses. Understanding phenotypic traits, such as entry, at this genus-wide level can revolutionise our ability to predict zoonotic potential. ### Competing Interest Statement The authors have declared no competing interest.
Increased immune evasion by emerging and highly mutated SARS-CoV-2 variants is a key challenge to the control of COVID-19. The majority of these mutations mainly target the spike protein, allowing the new variants to escape the immunity previously raised by vaccination and/or infection by earlier variants of SARS-CoV-2. In this study, we investigated the neutralizing capacity of antibodies against emerging variants of interest circulating between May 2023 and March 2024 using sera from representative samples of the Kenyan population. From our genomics data, we identified the most prevalent Kenyan and global variants and performed pseudoviruses neutralization assays with the most recent SARS-CoV-2 variants. Our data show that antibodies from individuals in the general population in Kenya were less effective against the recent prevalent SARS-CoV-2 omicron variants (i.e. EG.5.1, FY.4, BA.2.86, JN.1, and JN.1.4) compared to the ancestral wildtype strain. Although there was increased neutralization following multiple doses of vaccine, antibodies from >40% of the vaccinated individuals did not neutralize the omicron variants, suggesting that individuals were susceptible to infection by these variants. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the Wellcome Trust (grants 226141/Z/22/Z, 226130/Z/22/Z, 227131/Z/23/Z & 227131/B/23/Z 226141/Z/22/Z and 226002/A/22/Z), MRC (MR/W005611/1, MR/Y004205/1), BBSRC (BBS/E/I/COV07001, BBS/E/I/00007031), and Bill and Melinda Gates Foundation (INV-039626). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Kenya Medical Research Institute, Scientific Ethics Review Unit gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Add data produced are available online at https://doi.org/10.7910/DVN/6DSHMB
Peste des petits ruminants virus (PPRV) is a multi-host pathogen with sheep and goats as main hosts. To investigate the role of cattle in the epidemiology of PPR, we simulated conditions similar to East African zero-grazing husbandry practices in a series of trials with local Zebu cattle (Bos taurus indicus) co-housed with goats (Capra aegagrus hircus). Furthermore, we developed a mathematical model to assess the impact of PPRV-transmission from cattle to goats. Of the 32 cattle intranasally infected with the locally endemic lineage IV strain PPRV/Ethiopia/Habru/2014 none transmitted PPRV to 32 co-housed goats. However, these cattle or cattle co-housed with PPRV-infected goats seroconverted. The results confirm previous studies that cattle currently play a negligible role in PPRV-transmission and small ruminant vaccination is sufficient for eradication. However, the possible emergence of PPRV strains more virulent for cattle may impact eradication. Therefore, continued monitoring of PPRV circulation and evolution is recommended.