Recent Cholera Publications on PubMed

Cholera outbreak in Syria amid humanitarian crisis: the epidemic threat, future health implications, and response strategy - a review

July 6, 2023

Front Public Health. 2023 Jun 20;11:1161936. doi: 10.3389/fpubh.2023.1161936. eCollection 2023.

ABSTRACT

The war in Syria, which started over 11 years ago, has devastated the country's water sources, healthcare system, and other vital facilities for healthy living. The country is vulnerable to outbreaks, especially epidemic-prone ones like cholera, due to its fragile health system. Syria experienced its last hit of cholera in 2009, which led to the deaths of several Syrian children and affected about 1,000 people. The current cholera resurgence in Syria calls for public concern. Considering the poor access to clean water, the forced relocation of people, and other destruction caused by the war, these factors have exposed Syrian children to infectious diseases like cholera. We argued for more efforts toward the implementation of Water, Sanitation and Hygiene (WASH) in the country. We also pointed out the need for proper education and sensitization campaigns using all available resources to educate the populace, mass chlorination of wells, mapping vulnerable areas, and implementing WASH while encouraging vaccination coverage for cholera as a strategy to reduce its incidence. Improving the national surveillance systems will aid in the timely and appropriate reporting of any outbreak. Again, more negotiations should be done to seek a lasting solution to ending the war and restoring peace and serenity in the country.

PMID:37408746 | PMC:PMC10319003 | DOI:10.3389/fpubh.2023.1161936

Water, Sanitation, and Cholera in Sub-Saharan Africa

July 6, 2023

Environ Sci Technol. 2023 Jul 6. doi: 10.1021/acs.est.3c01317. Online ahead of print.

ABSTRACT

Improvements in water and sanitation should reduce cholera risk though the associations between cholera and specific water and sanitation access measures remain unclear. We estimated the association between eight water and sanitation measures and annual cholera incidence access across sub-Saharan Africa (2010-2016) for data aggregated at the country and district levels. We fit random forest regression and classification models to understand how well these measures combined might be able to predict cholera incidence rates and identify high cholera incidence areas. Across spatial scales, piped or "other improved" water access was inversely associated with cholera incidence. Access to piped water, septic or sewer sanitation, and septic, sewer, or "other improved" sanitation were associated with decreased district-level cholera incidence. The classification model had moderate performance in identifying high cholera incidence areas (cross-validated-AUC 0.81, 95% CI 0.78-0.83) with high negative predictive values (93-100%) indicating the utility of water and sanitation measures for screening out areas that are unlikely to be at high cholera risk. While comprehensive cholera risk assessments must incorporate other data sources (e.g., historical incidence), our results suggest that water and sanitation measures could alone be useful in narrowing the geographic focus for detailed risk assessments.

PMID:37409942 | DOI:10.1021/acs.est.3c01317

Azithromycin for bacterial watery diarrhea: A reanalysis of the AntiBiotics for Children with severe Diarrhea (ABCD) trial incorporating molecular diagnostics

July 5, 2023

J Infect Dis. 2023 Jul 5:jiad252. doi: 10.1093/infdis/jiad252. Online ahead of print.

ABSTRACT

BACKGROUND: Bacterial pathogens cause substantial diarrhea morbidity and mortality among children living in endemic settings, yet antimicrobial treatment is only recommended for dysentery or suspected cholera.

METHODS: AntiBiotics for Children with severe Diarrhea was a 7-country placebo-controlled double-blind efficacy trial of azithromycin in children 2-23 months of age with watery diarrhea accompanied by dehydration or malnutrition. We tested fecal samples for enteric pathogens utilizing quantitative PCR and employed pathogen-specific cutoffs based on genomic target quantity in previous case control diarrhea etiology studies to identify likely and possible bacterial etiologies.

RESULTS: Among 6,692 children, the leading likely etiologies were rotavirus(21.1%), ST-ETEC(13.3%), Shigella(12.6%) and Cryptosporidium(9.6%). More than one quarter (1894[28.3%]) had a likely and 1,153(17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin vs. placebo among children with a likely bacterial etiology (Risk Difference[RD]likely: -11.6[95%CI:-15.6, -7.6] and possible bacterial etiology (RDpossible:-8.7 [95%CI:-13.0, -4.4]) but not in other children (RDunlikely:-0.3%[95%CI:-2.9%,2.3%]). A similar association was observed for 90-day hospitalization or death (RDlikely:-3.1[95%CI:-5.3, -1.0], RDpossible: -2.3[95%CI: -4.5, -0.01], and (RDunlikely:-0.6 [95%CI:-1.9,0.6]). The magnitude of risk differences were similar among specific likely bacterial etiologies, including Shigella.

CONCLUSION: Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment.

PMID:37405406 | DOI:10.1093/infdis/jiad252

Upsurge in hospitalization of pediatric patients with severe acute respiratory infections in Kolkata and surrounding districts caused by recombinant human respiratory adenovirus type B 7/3

July 3, 2023

J Med Virol. 2023 Jul;95(7):e28897. doi: 10.1002/jmv.28897.

ABSTRACT

Globally, different genotypes of human adenoviruses are associated with outbreaks of acute respiratory infection (ARI) though such evidence is lacking from India. In the present study, we report a sudden increase in the positivity of respiratory adenovirus among hospitalized children with ARI from Kolkata and the surrounding districts of West Bengal, India, from December 2022 to date. A sharp rise in the positivity rate of respiratory adenovirus was found which ranged from 22.1% in early December 2022 to 52.6% in mid-March 2023. The overall positivity was 40.4% during the period and children in the 2 to <5 years (51.0%) age group were mostly affected. Single infection with adenovirus was found in 72.4% of cases while co-infection with rhinovirus was the maximum (9.4%). Around 97.5% of positive cases required hospitalization. Cough, breathlessness, and wheeze were the most common clinical features among positive patients. Phylogenetic analysis of the hexon and fiber gene of all the sequenced strains revealed HAdV-B 7/3 recombination with more than 99% homology within themselves. This report of a respiratory adenovirus outbreak in West Bengal, India causing severe illness in the pediatric population underscores the need for regular monitoring of the circulating strains.

PMID:37394792 | DOI:10.1002/jmv.28897

Preliminary Evaluation of <em>Lablab purpureus</em> Phytochemicals for Anti-BoHV-1 Activity Using In Vitro and In Silico Approaches

July 3, 2023

ACS Omega. 2023 Jun 14;8(25):22684-22697. doi: 10.1021/acsomega.3c01478. eCollection 2023 Jun 27.

ABSTRACT

Lablab purpureus from the Fabaceae family has been reported to have antiviral properties and used in traditional medical systems like ayurveda and Chinese medicine and has been employed to treat a variety of illnesses including cholera, food poisoning, diarrhea, and phlegmatic diseases. The bovine alphaherpesvirus-1 (BoHV-1) is notorious for causing significant harm to the veterinary and agriculture industries. The removal of the contagious BoHV-1 from host organs, particularly in those reservoir creatures, has required the use of antiviral drugs that target infected cells. This study developed LP-CuO NPs from methanolic crude extracts, and FTIR, SEM, and EDX analyses were used to confirm their formation. SEM analysis revealed that the LP-CuO NPs had a spherical shape with particle sizes between 22 and 30 nm. Energy-dispersive X-ray pattern analysis revealed the presence of only copper and oxide ions. By preventing viral cytopathic effects in the Madin-Darby bovine kidney cell line, the methanolic extract of Lablab purpureus and LP-CuO NPs demonstrated a remarkable dose-dependent anti-BoHV-1 action in vitro. Furthermore, molecular docking and molecular dynamics simulation studies of bio-actives from Lablab purpureus against the BoHV-1 viral envelope glycoprotein disclosed effective interactions between all phytochemicals and the protein, although kievitone was found to have the highest binding affinity, with the greatest number of interactions, which was also validated with molecular dynamics simulation studies. Understanding the chemical reactivity qualities of the four ligands was taken into consideration facilitated by the global and local descriptors, which aimed to predict the chemical reactivity descriptors of the studied molecules through the conceptual DFT methodology, which, along with ADMET finding, support the in vitro and in silico results.

PMID:37396248 | PMC:PMC10308559 | DOI:10.1021/acsomega.3c01478

Population genomics of diarrheagenic Escherichia coli uncovers high connectivity between urban and rural communities in Ecuador

July 1, 2023

Infect Genet Evol. 2023 Jun 29:105476. doi: 10.1016/j.meegid.2023.105476. Online ahead of print.

ABSTRACT

Human movement may be an important driver of transmission dynamics for enteric pathogens but has largely been underappreciated except for international 'travelers' diarrhea or cholera. Phylodynamic methods, which combine genomic and epidemiological data, are used to examine rates and dynamics of disease matching underlying evolutionary history and biogeographic distributions, but these methods often are not applied to enteric bacterial pathogens. We used phylodynamics to explore the phylogeographic and evolutionary patterns of diarrheagenic E. coli in northern Ecuador to investigate the role of human travel in the geographic distribution of strains across the country. Using whole genome sequences of diarrheagenic E. coli isolates, we built a core genome phylogeny, reconstructed discrete ancestral states across urban and rural sites, and estimated migration rates between E. coli populations. We found minimal structuring based on site locations, urban vs. rural locality, pathotype, or clinical status. Ancestral states of phylogenomic nodes and tips were inferred to have 51% urban ancestry and 49% rural ancestry. Lack of structuring by location or pathotype E. coli isolates imply highly connected communities and extensive sharing of genomic characteristics across isolates. Using an approximate structured coalescent model, we estimated rates of migration among circulating isolates were 6.7 times larger for urban towards rural populations compared to rural towards urban populations. This suggests increased inferred migration rates of diarrheagenic E. coli from urban populations towards rural populations. Our results indicate that investments in water and sanitation prevention in urban areas could limit the spread of enteric bacterial pathogens among rural populations.

PMID:37392822 | DOI:10.1016/j.meegid.2023.105476

The Cholera Outbreak in Lebanon: October 2022

June 29, 2023

Disaster Med Public Health Prep. 2023 Jun 29;17:e422. doi: 10.1017/dmp.2023.76.

ABSTRACT

In recent years, Lebanon has been struggling with a socioeconomic crisis exacerbated by population displacement after the Syrian crisis, which put a significant burden on its healthcare system. An additional challenge has been the response to a cholera outbreak- a deadly waterborne disease transmitted through the fecal-oral route that usually manifests as severe watery diarrhea and can rapidly progress to death. After reports of a cholera outbreak in Syria were disclosed in September 2022, the Northern Governorate of Lebanon too began reporting cases immediately after, and the first case was confirmed on October 6, 2022. The outbreak rapidly spread to other parts of the country. As of December 9, 2022, a total of 5105 suspected cholera cases with 23 associated deaths were reported across Lebanon. An estimated 45% of these cases were of children and adolescents below the age of 15 years. With the start of the vaccination campaign, awareness programs emphasizing adequate sanitation and clean water sources have become an urgent need.

PMID:37381669 | DOI:10.1017/dmp.2023.76

Historical events in epidemiology, at the Muñiz Hospital, Buenos Aires, Argentina

June 28, 2023

Medicina (B Aires). 2023;83(3):442-454.

ABSTRACT

The Muñiz hospital is an institution with historical, cultural and health heritage. A historical analysis of the different epidemics/pandemics and outbreaks is carried out here, assessing the epidemiological management (surveillance, prevention, control and emergency management) in the institution and the reason for its architecture. To this end, a systematic review of the literature on the history of the Muñiz hospital and its references was carried out, since 1980 to 2023, following the PRISMA format. Thirty-six publications were found that met the required methodological and epidemiological criteria. The review shows the relevant health problems, the events present in an epidemic/ pandemic, the importance of preventive measures and to assess the need for a continuous epidemiological surveillance system, as well as the contribution of historical methodological references that allow obtaining useful information in the health area. We have addressed great historical moments in epidemiology, explaining the management of diseases or epidemics/pandemics at the Muñiz hospital, which were largely related to the society of the time (paradigms). It should be noted that population growth spread diseases throughout the planet, generating threats, and that epidemics/pandemics transformed societies and quite possibly have decisively changed the course of history, as happened with the COVID-19 pandemic.

PMID:37379541

Bacteremia Caused by a Serotype Ob5 Vibrio cholerae Strain in a Cirrhotic Patient in China

June 28, 2023

Microbiol Spectr. 2023 Jun 28:e0205423. doi: 10.1128/spectrum.02054-23. Online ahead of print.

ABSTRACT

The increasing incidence of non-O1/non-O139 Vibrio cholerae (NOVC) has been observed worldwide. However, septicemia caused by NOVC remains a rare condition that has received limited attention. Currently, there are no established treatment guidelines for bloodstream infections caused by NOVC, and the understanding of this condition mainly relies on individual case reports. Although NOVC bacteremia can be fatal in a small percentage of cases, knowledge about its microbiological features remains limited. Here, we present a case of V. cholerae septicemia caused by NOVC in a 46-year-old man with chronic viral hepatitis and liver cirrhosis. The isolated strain, named V. cholerae VCH20210731 and classified as a new sequence type (ST), ST1553, was found to be susceptible to most of the antimicrobial agents tested. O-antigen serotyping of V. cholerae VCH20210731 revealed that it belonged to serotype Ob5. Interestingly, the ctxAB genes, which are typically associated with V. cholerae, were absent in VCH20210731. However, the strain possessed 25 other potential virulence genes, such as hlyA, luxS, hap, and rtxA. The resistome of V. cholerae VCH20210731 included several genes, including qnrVC4, crp, almG, and parE. Nevertheless, susceptibility testing demonstrated that the isolate was susceptible to most of the antimicrobial agents tested. Phylogenetic analysis indicated that the closest strain to VCH20210731 was strain 120 from Russia, differing by 630 single-nucleotide polymorphisms (SNPs). Our findings contribute to the understanding of the genomic epidemiological characteristics and antibiotic resistance mechanisms of this invasive bacterial pathogen. IMPORTANCE This study highlights the discovery of a novel ST1553 V. cholerae strain in China, providing valuable insights into the genomic epidemiology and global transmission dynamics of V. cholerae. It is important to note that clinical presentations of NOVC bacteremia can vary significantly, and the isolates demonstrate genetic diversity. Consequently, health care professionals and public health experts should remain vigilant about the potential for infection with this pathogen, particularly considering the elevated prevalence of liver disease in China.

PMID:37378569 | DOI:10.1128/spectrum.02054-23

A Decade-Long Evaluation of Neonatal Septicaemic Escherichia coli: Clonal Lineages, Genomes, and New Delhi Metallo-Beta-Lactamase Variants

June 27, 2023

Microbiol Spectr. 2023 Aug 17;11(4):e0521522. doi: 10.1128/spectrum.05215-22. Epub 2023 Jun 27.

ABSTRACT

Longitudinal studies of extraintestinal pathogenic Escherichia coli (ExPEC) and epidemic clones of E. coli in association with New Delhi metallo-β-lactamase (blaNDM) in septicaemic neonates are rare. This study captured the diversity of 80 E. coli isolates collected from septicaemic neonates in terms of antibiotic susceptibility, resistome, phylogroups, sequence types (ST), virulome, plasmids, and integron types over a decade (2009 to 2019). Most of the isolates were multidrug-resistant and, 44% of them were carbapenem-resistant, primarily due to blaNDM. NDM-1 was the sole NDM-variant present in conjugative IncFIA/FIB/FII replicons until 2013, and it was subsequently replaced by other variants, such as NDM-5/-7 found in IncX3/FII. A core genome analysis for blaNDM+ve isolates showed the heterogeneity of the isolates. Fifty percent of the infections were caused by isolates of phylogroups B2 (34%), D (11.25%), and F (4%), whereas the other half were caused by phylogroups A (25%), B1 (11.25%), and C (14%). The isolates were further distributed in approximately 20 clonal complexes (STC), including five epidemic clones (ST131, ST167, ST410, ST648, and ST405). ST167 and ST131 (subclade H30Rx) were dominant, with most of the ST167 being blaNDM+ve and blaCTX-M-15+ve. In contrast, the majority of ST131 isolates were blaNDM-ve but blaCTX-M-15+ve, and they possessed more virulence determinants than did ST167. A single nucleotide polymorphism (SNP)-based comparative genome analysis of epidemic clones ST167 and ST131 in a global context revealed that the study isolates were present in close proximity but were distant from global isolates. The presence of antibiotic-resistant epidemic clones causing sepsis calls for a modification of the recommended antibiotics with which to treat neonatal sepsis. IMPORTANCE Multidrug-resistant and virulent ExPEC causing sepsis in neonates is a challenge to neonatal health. The presence of enzymes, such as carbapenemases (blaNDM) that hydrolyze most β-lactam antibiotic compounds, result in difficulties when treating neonates. The characterization of ExPECs collected over 10 years showed that 44% of ExPECs were carbapenem-resistant, possessing transmissible blaNDM genes. The isolates belonged to different phylogroups that are considered to be either commensals or virulent. The isolates were distributed in around 20 clonal complexes (STC), including two predominant epidemic clones (ST131 and ST167). ST167 possessed few virulence determinants but was blaNDM+ve. In contrast, ST131 harbored several virulence determinants but was blaNDM-ve. A comparison of the genomes of these epidemic clones in a global context revealed that the study isolates were present in close proximity but were distant from global isolates. The presence of epidemic clones in a vulnerable population with contrasting characteristics and the presence of resistance genes call for strict vigilance.

PMID:37367488 | PMC:PMC10434172 | DOI:10.1128/spectrum.05215-22

Genomic epidemiology of Vibrio cholerae during a mass vaccination campaign of displaced communities in Bangladesh

June 24, 2023

Nat Commun. 2023 Jun 24;14(1):3773. doi: 10.1038/s41467-023-39415-3.

ABSTRACT

Ongoing diarrheal disease surveillance throughout Bangladesh over the last decade has revealed seasonal localised cholera outbreaks in Cox's Bazar, where both Bangladeshi Nationals and Forcibly Displaced Myanmar Nationals (FDMNs) reside in densely populated settlements. FDMNs were recently targeted for the largest cholera vaccination campaign in decades. We aimed to infer the epidemic risk of circulating Vibrio cholerae strains by determining if isolates linked to the ongoing global cholera pandemic ("7PET" lineage) were responsible for outbreaks in Cox's Bazar. We found two sublineages of 7PET in this setting during the study period; one with global distribution, and a second lineage restricted to Asia and the Middle East. These subclades were associated with different disease patterns that could be partially explained by genomic differences. Here we show that as the pandemic V. cholerae lineage circulates in this vulnerable population, without a vaccine intervention, the risk of an epidemic was very high.

PMID:37355673 | DOI:10.1038/s41467-023-39415-3

Imported Cholera Cases, South Africa, 2023

June 23, 2023

Emerg Infect Dis. 2023 Aug;29(8):1687-1690. doi: 10.3201/eid2908.230750. Epub 2023 Jun 23.

ABSTRACT

Since February 2022, Malawi has experienced a cholera outbreak of >54,000 cases. We investigated 6 cases in South Africa and found that isolates linked to the outbreak were Vibrio cholerae O1 serotype Ogawa from seventh pandemic El Tor sublineage AFR15, indicating a new introduction of cholera into Africa from south Asia.

PMID:37352549 | DOI:10.3201/eid2908.230750

News Brief: The World Health Organization warns of a high global cholera risk

June 22, 2023

Am J Nurs. 2023 Jul 1;123(7):12. doi: 10.1097/01.NAJ.0000944872.06439.ed.

NO ABSTRACT

PMID:37345767 | DOI:10.1097/01.NAJ.0000944872.06439.ed

Impact of climate change on waterborne infections and intoxications

June 21, 2023

J Health Monit. 2023 Jun 1;8(Suppl 3):62-77. doi: 10.25646/11402. eCollection 2023 Jun.

ABSTRACT

Progressive climate change holds the potential for increasing human health risks from waterborne infections and intoxications, e. g. through an increase in pathogen concentrations in water bodies, through the establishment of new pathogens or through possible changes in pathogen properties. This paper presents some examples of potential impacts of climate change in Germany. Non-cholera Vibrio occur naturally in seawater, but can proliferate significantly in shallow water at elevated temperatures. In the case of Legionella, climate change could lead to temporary or longer-term increased incidences of legionellosis due to the combination of warm and wet weather. Higher temperatures in piped cold water or lower temperatures in piped hot water may also create conditions conducive to higher Legionella concentrations. In nutrient-rich water bodies, increased concentrations of toxigenic cyanobacteria may occur as temperatures rise. Heavy rainfall following storms or prolonged periods of heat and drought can lead to increased levels of human pathogenic viruses being washed into water bodies. Rising temperatures also pose a potential threat to human health through pathogens causing mycoses and facultatively pathogenic micro-organisms: increased infection rates with non-tuberculous mycobacteria or fungi have been documented after extreme weather events.

PMID:37342430 | PMC:PMC10278370 | DOI:10.25646/11402

Accumulation of Biological and Behavioral Data of Female Sex Workers Using Respondent-Driven Sampling: Protocol for a Systematic Review

June 19, 2023

JMIR Res Protoc. 2023 Jun 19;12:e43722. doi: 10.2196/43722.

ABSTRACT

BACKGROUND: Respondent-driven sampling (RDS) is a nonprobability sampling technique that allows the extrapolation of its outcome to the target population. This approach is typically used to overcome the difficulties in studying hidden or difficult-to-reach groups.

OBJECTIVE: The purpose of this protocol is to generate a systematic review on the accumulation of biological and behavioral data of female sex workers (FSWs) through different surveys that use the RDS method from around the world in the near future. The future systematic review will discuss the initiation, actualization, and problems of RDS during the accumulation of biological and behavioral data of FSWs through surveys from around the world.

METHODS: The behavior and biological data of FSWs will be extracted from peer-reviewed studies published between 2010 and 2022 and that are acquired through RDS. Using PubMed, Google Scholar, the Cochrane database, Scopus, Science Direct, and the Global Health network, all papers that are available will be obtained using the search phrases "respondent-driven" and "Female Sex Workers" OR "FSW" OR "sex workers" OR "SW." According to STROBE-RDS (Strengthening the Reporting of Observational Studies in Epidemiology for Respondent-Driven Sampling) criteria, the data will be retrieved through a data extraction form and will be organized using World Health Organization classifications of areas. The Newcastle-Ottawa Quality Assessment Scale will be used to measure bias risk and overall study quality.

RESULTS: The future systematic review that will be generated from this protocol will offer evidence for or against the claim that using the RDS technique to recruit participants from "hidden" or "hard-to-reach" populations is the best strategy. The results will be disseminated through a peer-reviewed publication. Data collection started on April 1, 2023, and the systematic review is expected to be published by December 15, 2023.

CONCLUSIONS: A minimum set of parameters for specific methodological, analytical, and testing procedures, including RDS methods to evaluate the overall quality of any RDS survey, will be provided by the future systematic review, in accordance with this protocol, to assist researchers, policy makers, and service providers in improving RDS methods for the surveillance of any key population.

TRIAL REGISTRATION: PROSPERO CRD42022346470; https://tinyurl.com/54xe2s3k.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/43722.

PMID:37335607 | DOI:10.2196/43722

A stitch in time: The importance of water and sanitation services (WSS) infrastructure maintenance for cholera risk. A geospatial analysis in Harare, Zimbabwe

June 16, 2023

PLoS Negl Trop Dis. 2023 Jun 16;17(6):e0011353. doi: 10.1371/journal.pntd.0011353. eCollection 2023 Jun.

ABSTRACT

Understanding the factors associated with cholera outbreaks is an integral part of designing better approaches to mitigate their impact. Using a rich set of georeferenced case data from the cholera epidemic that occurred in Harare from September 2018 to January 2019, we apply spatio-temporal modelling to better understand how the outbreak unfolded and the factors associated with higher risk of being a reported case. Using Call Detail Records (CDR) to estimate weekly population movement of the community throughout the city, results suggest that broader human movement (not limited to infected agents) helps to explain some of the spatio-temporal patterns of cases observed. In addition, results highlight a number of socio-demographic risk factors and suggest that there is a relationship between cholera risk and water infrastructure. The analysis shows that populations living close to the sewer network, with high access to piped water are associated with at higher risk. One possible explanation for this observation is that sewer bursts led to the contamination of the piped water network. This could have turned access to piped water, usually assumed to be associated with reduced cholera risk, into a risk factor itself. Such events highlight the importance of maintenance in the provision of SDG improved water and sanitation infrastructure.

PMID:37327203 | PMC:PMC10275451 | DOI:10.1371/journal.pntd.0011353

Production of a promising modular proteinaceous self-assembled delivery system for vaccination

June 16, 2023

Nanoscale. 2023 Jun 16. doi: 10.1039/d2nr06718h. Online ahead of print.

ABSTRACT

Recently, there have been enormous advances in nano-delivery materials, especially safer and more biocompatible protein-based nanoparticles. Generally, proteinaceous nanoparticles (such as ferritin and virus-like particles) are self-assembled from some natural protein monomers. However, to ensure their capability of assembly, it is difficult to upgrade the protein structure through major modifications. Here, we have developed an efficient orthogonal modular proteinaceous self-assembly delivery system that could load antigens with an attractive coupling strategy. In brief, we constructed a nanocarrier by fusing two orthogonal domains-a pentameric cholera toxin B subunit and a trimer forming peptide-and an engineered streptavidin monomer for binding biotinylated antigens. After successfully preparing the nanoparticles, the receptor-binding domain of SARS-CoV-2 spike protein and influenza virus haemagglutination antigen are used as model antigens for further evaluation. We found that the biotinylated antigen is able to bind to the nanoparticles with high affinity and achieve efficient lymph node drainage when loaded on the nanoparticles. Then, T cells are greatly activated and the formation of germinal centers is observed. Experiments of two mouse models demonstrate the strong antibody responses and prophylactic effects of these nanovaccines. Thus, we establish a proof-of-concept for the delivery system with the potential to load diverse antigen cargos to generate high-performance nanovaccines, thereby offering an attractive platform technology for nanovaccine preparation.

PMID:37326289 | DOI:10.1039/d2nr06718h

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