Biology subjects

Happi, C.

Publications and source records attributed to Happi, C..

8 recordsLinked to original sources

bioRxiv2026

Simultaneous broad protection against Ebola Sudan, Marburg and Lassa viruses conferred by a DNA primed MVA-vectored multivalent vaccine

Sub-Saharan Africa continues to experience recurrent outbreaks of zoonotic viral diseases that spill over unpredictably from animal reservoirs into human populations. In many regions, mpox co-circulates with viral hemorrhagic fevers (VHFs) caused by Ebola Sudan virus (SUDV), Marburg virus (MARV), and Lassa fever virus (LASV). Overlapping clinical syndromes that these VHF cause challenge surveillance, diagnostics and timely deployment of effective countermeasures. A single vaccine capable of protecting against these biologically and genetically distinct pathogens would markedly reduce the cost and complexity of outbreak response, lessen dependence on emergency international aid, and strengthen long-term health system resilience. Here, we report on the development of an MVA-based mpox vaccine engineered to express computationally designed, broad-coverage antigens targeting SUDV, MARV and LASV. In preclinical challenge studies, this multivalent vaccine elicited robust immune responses and conferred significant protection against lethal infection from all three pathogens in parallel challenge experiments. These findings establish preclinical proof-of-concept for a single, broadly protective VHF vaccine and support its clinical development for deployment across diverse settings in Sub-Saharan Africa. SignificanceOutbreak control in Sub-Saharan Africa is challenged by the co-circulation of different high consequence human infections such as mpox and diverse viral hemorrhagic fevers (VHF) such as SUDV, MARV, and LASV pathogens. These VHFs have overlapping early clinical syndromes, complicating triage and delaying effective targeted interventions. We developed a single MVA-based vaccine encoding computationally designed, conserved antigens from all three VHFs encoded within the MVA vector analogous to the licensed mpox vaccine. In simultaneous challenge models, this multivalent vaccine elicited robust humoral and cellular responses and conferred significant protection against lethal infection by each hemorrhagic fever pathogen. This work provides preclinical proof-of-concept for a unified, broadly protective countermeasure compatible with existing MVA-mpox vaccine manufacturing and deployment experience. By reducing dependence on rapid differential diagnostics and streamlining logistics relative to maintaining multiple pathogen-specific vaccine stockpiles, this approach can lower costs, accelerate response, and increase equity of access during syndromic outbreaks. The platforms engineered antigen breadth and human safety profile of MVA together support a pragmatic translational pathway toward clinical evaluation and regional readiness for zoonotic spillover events that are intensifying with human and environmental changes.

immunology↗

bioRxiv2025

Delphy: scalable, near-real-time Bayesian phylogenetics for outbreaks

Pathogen genomic analysis is central to tracking, understanding, and containing outbreaks, but complexity and high costs of state-of-the-art (SOTA) phylogenetic tools limit global access and impact. We introduce Delphy, an exact reformulation of Bayesian phylogenetics designed to transform its speed, scalability and accessibility while retaining SOTA accuracy. Delphys central data structure, an Explicit Mutation Annotated Tree, exploits the high sequence similarity in large-scale epidemic datasets for efficient tree exploration and convergence. By reproducing key analyses from recent major epidemics (Ebola, Zika, SARS-CoV-2, mpox, and H5N1), we demonstrate SOTA accuracy with up to 1,000x speedups. Assessing Delphys scalability, we show that a simulated dataset of 100,000 sequences can be analyzed in under a day-the largest such computation to date. We distribute Delphy as a client-side web application, enabling users worldwide to turn raw data into interactive results within minutes, without the data ever leaving the users machine. Delphy automatically identifies key viral lineages and mutations, as well as their emergence and prevalence through time, all with quantified uncertainties derived from a solid theoretical foundation. Delphy shows the power of Bayesian phylogenetics as a fast, accessible frontline tool for tackling future outbreaks.

genomics↗

bioRxiv2024

Nationwide surveillance identifies yellow fever and chikungunya viruses transmitted by various species of Aedes mosquitoes in Nigeria

BackgroundSince its reemergence in 2017, yellow fever (YF) has been active in Nigeria. The Nigeria Centre for Disease Control (NCDC) has coordinated responses to the outbreaks with the support of the World Health Organization (WHO). The National Arbovirus and Vectors Research Centre (NAVRC) handles the vector component of these responses. This study sought to identify the vectors driving YF transmission and any of the targeted arboviruses and their distribution across states. MethodsEggs, larvae and pupae as well as adult mosquitoes were collected in observational, analytical, and cross-sectional surveys conducted in sixteen YF outbreak states between 2017 and 2020. Adult mosquitoes (field-collected or reared from immature stages) were morphologically identified, and arboviruses were detected using RT-qPCR at the African Centre of Excellence for Genomics of Infectious Diseases (ACEGID). ResultsAedes mosquitoes were collected in eleven of the sixteen states surveyed and the mosquitoes in nine states were found infected with arboviruses. A total of seven Aedes species were collected from different parts of the country. Aedes aegypti was the most dominant (51%) species, whereas Aedes africanus was the least (0.2%). Yellow fever virus (YFV) was discovered in 33 ([~]26%) out of the 127 Aedes mosquito pools. In addition to YFV, the Chikungunya virus (CHIKV) was found in nine pools. Except for Ae. africanus, all the Aedes species tested positive for at least one arbovirus. YFV-positive pools were found in six (6) Aedes species while CHIKV-positive pools were only recorded in two Aedes species. Edo State had the most positive pools (16), while Nasarawa, Imo, and Anambra states had the least (1 positive pool). Breteau and house indices were higher than normal transmission thresholds in all but one state. ConclusionIn Nigeria, there is a substantial risk of arbovirus transmission by Aedes mosquitoes, with YFV posing the largest threat at the moment. This risk is heightened by the fact that YFV and CHIKV have been detected in vectors across outbreak locations. Hence, there is an urgent need to step up arbovirus surveillance and control activities in the country. Author summaryEpidemics of arboviral infections are fast becoming the norm across Africa, especially in Nigeria, where sporadic epidemics of Aedes-borne Yellow Fever (YF) have been on the rise since 2017. A nationwide surveillance was conducted to detect the arboviruses and the vectors transmitting them during large YF outbreaks across Nigeria. Aedes mosquitoes collected from 57 local government areas/outbreak locations, covering 16 out of the 36 states in Nigeria, were reared to adulthood, morphologically identified to species level and assayed using qRT-PCR to detect six epidemiologically important arboviruses (Dengue, Chikungunya (CHIKV), Zika, YF, West Nile and Onyong nyong). Seven Aedes species (including Ae. aegypti, Ae. albopictus, Ae. circumluteolus, Ae. vittatus, Ae. simpsoni complex, Ae. luteocephalus, and Ae. africanus), were caught, with Ae. aegypti and Ae. albopictus the most widespread and predominant. Only YF and CHKV were found in mosquito pools from 9 states, with only Ae. aegypti pools positive for CHKV, while YF virus was found predominantly in this species and Ae. albopictus. This study provides a baseline for widespread distribution of the major Aedes vectors, and their arboviral transmission profiles, which can enhance evidence-based control measures, and strengthen nationwide surveillance systems to forestall future outbreaks of public health magnitude.

zoology↗

bioRxiv2023

Genomic Characterisation of Multidrug-Resistant Pathogenic Enteric Bacteria from healthy children in Osun State, Nigeria

Antimicrobial resistance (AMR) has been established to be a significant driver for the persistence and spread of bacterial infections. It is, therefore, essential to conduct epidemiological surveillance of AMR in healthy individuals to understand the actual dynamics of AMR in Nigeria. Multi-drug resistant Klebsiella quasivariicola (n=1), Enterobacter hormaechei (n=1), and Escherichia coli (n=3) from stool samples of healthy children were subjected to whole genome sequencing using Illumina Nextseq1000/2000 and Oxford nanopore. Bioinformatics analysis reveals antimicrobial resistance, virulence genes, and plasmids. This pathogenic enteric bacteria harbored more than three plasmid replicons of either Col and/or Inc type associated with outbreaks and AMR resistant gene pmrB responsible for colistin resistance. Plasmid reconstruction revealed an integrated tetA gene responsible for tetracycline resistance, and caa gene responsible for toxin production in two of the E.coli isolates, and a cusC gene known to induce neonatal meningitis in the K. quasivariicola ST3879. The global spread of MDR pathogenic enteric bacteria is a worrying phenomenon, and close surveillance of healthy individuals, especially children, is strongly recommended to prevent the continuous spread and achieve the elimination and eradication of these infections. Molecular epidemiological surveillance using whole genome sequencing (WGS) will improve the detection of MDR pathogens in Nigeria.

microbiology↗

bioRxiv2022

Emergence and Genomic Characterization of Multidrug resistant Candida auris in West Africa.

Candida auris is an emerging multidrug-resistant fungal pathogen that has become a worldwide public health threat due to limitations of treatment options, difficulty in diagnosis, and its potential for clonal transmission. Antifungal suceptibility tests and next generation sequencing were carried out on cultured isolates. Bioinformatics analysis was done using variant calling methods and genome-wide short nucleotide polymorphism (SNP) based phylogeny. Here, we report the first four cases of C. auris infection and colonization reported in West Africa. A total of four isolates from four reported cases of candidemia were analyzed. Three patients had fungaemia, which led to fatal invasive infection and the last patient was a likely case of colonization. Of the four patients, two had mutations which conferred resistance to the antifungal azole group and other non-synonymous mutations in hotspot genes such as ERG2, ERG11 and FKS1. Isolates from these patients clustered to clades I and IV, which indicates more than one introduction of C.auris into Nigeria. The first report of C. auris in Nigeria and West Africa is of public health importance as this report will aid identification, surveillance and intervention of resistant drug resistant candidiasis in the region.

microbiology↗

bioRxiv2020

Microbial Metagenomic Approach Uncovers the First Rabbit Haemorrhagic Disease Virus genome in Sub-Saharan Africa

Rabbit Haemorrhagic Disease (RHD) causes high morbidity and mortality in rabbits and hares. Here, we report the first genomic characterization of Rabbit Hemorrhagic Disease Virus (RHDV) from sub-Saharan Africa. While suspected, only a single PCR finding without sequence confirmation or characterization has been reported. Here, we used a microbial metagenomic approach to confirm and characterize pathogens causing the suspected outbreak of RHD in Ibadan, Nigeria. On the 25th September 2020, the liver, spleen, and lung samples of five rabbits from an outbreak in 2 farms in Ibadan, Nigeria, were analyzed for the vp60 gene of RHDV by RT-PCR. Subsequently, Next Generation Sequencing on 1st of October revealed one full and two partial RHDV2 genomes on both farms. Phylogenetic analysis showed close clustering with RHDV2 lineages from Europe, in particular, 98.6% similarity with RHDV2 in the Netherlands, and 99.1 to 100% identity with RHDV2 in Germany, suggesting potential importation from Europe. The detection of twelve unique mutations in RHDV2 sequences from the Ibadan outbreak compared to other RHDV2 sequences in the same clade suggests significant genetic diversity of the GI.2 strains in Nigeria. This highlights the need to further understand the genetic diversity of Lagoviruses to, inform vaccine development, and for accurate tracking, monitoring, and control of outbreaks in Africa.

molecular biology↗

bioRxiv2020

Pan-genome analysis of Mycobacterium africanum: insights to dynamics and evolution

Mycobacterium tuberculosis complex (MTBC) consists of seven major lineages with three of them reported to circulate within West Africa: lineage 5 (West African 1) and lineage 6 (West African 2) which are geographically restricted to West Africa and lineage 4 (Euro-American lineage) which is found globally. It is unclear why the West African lineages are not found elsewhere; some hypotheses suggest that it could either be harboured by an animal reservoir which is restricted to West Africa, or strain preference for hosts of West African ethnicity, or inability to compete with other lineages in other locations. We tested the hypothesis that M. africanum (MAF) might have emigrated out of West Africa but was outcompeted by more virulent strains of M. tuberculosis (MTB). Whole genome sequences of MTB from Nigeria (n=21), China (n=21) and MAF from Mali (n=24) were retrieved, and a pan-genome analysis was performed after fully annotating these genomes. The outcome of this analysis shows that Lineages 4, 5 and 6 have relatively close pan-genomes whilst lineage 2 has an open pan-genome. We also see a correlation in numbers of some multiple copy core genes and amino acid substitution with lineage specificity that may have contributed to geographical distribution of these lineages. The findings in this study provides a perspective to one of the hypotheses that M. africanum might find it difficult to compete against the more modern lineages outside West Africa hence its localization to the geographical region.

genomics↗

bioRxiv2018

Capturing diverse microbial sequence with comprehensive and scalable probe design

Metagenomic sequencing has the potential to transform microbial detection and characteri zation, but new tools are needed to improve its sensitivity. We developed CATCH (Compact Aggregation of Targets for Comprehensive Hybridization), a computational method to enhance nucleic acid capture for enrichment of diverse microbial taxa. CATCH designs compact probe sets that achieve full coverage of known sequence diversity and that scale well with this diversity. To illustrate applications of CATCH, we focused on capturing viral genomes. We designed, synthesized, and validated multiple probe sets, including one that targets whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriched unique viral content on average 18x and allowed us to assemble genomes that we could not otherwise recover, while accurately preserving within-sample diversity. We used this approach to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of viral infections in samples with unknown content. Together, this work demonstrates a path toward more sensitive, cost-effective metagenomic sequencing.

genomics↗