Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 193 Records) |
Query Trace: Vinje J[original query] |
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Evaluation of crAssphages as a potential marker of human viral contamination in environmental water and fresh leafy greens
Suh SH , Lee JS , Kim SH , Vinjé J , Kim SH , Park GW . Front Microbiol 2024 15 1374568 CrAssphages are human gut bacteriophages with potential use as an indicator of human fecal contamination in water and other environmental systems. We determined the prevalence and abundance of crAssphages in water, food, and fecal samples and compared these estimates with the prevalence of norovirus. Samples were tested using two crAssphage-specific qPCR assays (CPQ056 and TN201-203) and for norovirus using TaqMan realtime RT-PCR. CrAssphage was detected in 40% of human fecal specimens, 61% of irrigation water samples, 58.5% of stream water samples, and 68.5% of fresh leafy greens samples. Interestingly, across all sample categories, crAssphage concentrations were 2-3 log10 higher than norovirus concentrations. The correlation of detection of crAssphage and norovirus was significant for the irrigation water samples (r = 0.74, p = 7.4e-06). Sequences obtained from crAssphage positive samples from human fecal and stream water samples phylogenetically clustered with genotype I crAssphages, whereas sequences derived from irrigation water samples clustered differently from other genotypes. Our data show that crAssphages were prevalent in norovirus-positive water samples and in fresh leafy green samples, there was a strong correlation between the presence of crAssphage and norovirus. CrAssphage genomic copies were consistently higher than norovirus copies in all sample types. Overall, our findings suggest that crAssphages could be used as reliable indicators to monitor fecal-borne virus contamination within the food safety chain. |
Human intestinal enteroids platform to assess the infectivity of gastroenteritis viruses in wastewater
Carmona-Vicente N , Pandiscia A , Santiso-Bellón C , Perez-Cataluña A , Rodríguez-Díaz J , Costantini VP , Buesa J , Vinjé J , Sánchez G , Randazzo W . Water Res 2024 255 121481 Fecal-orally transmitted gastroenteritis viruses, particularly human noroviruses (HuNoVs), are a public health concern. Viral transmission risk through contaminated water results underexplored as they have remained largely unculturable until recently and the robust measuring of gastroenteritis viruses infectivity in a single cell line is challenging. This study primarily aimed to test the feasibility of the human intestinal enteroids (HIE) model to demonstrate the infectivity of multiple gastroenteritis viruses in wastewater. Initially, key factors affecting viral replication in HIE model were assessed, and results demonstrated that the reagent-assisted disruption of 3D HIE represents an efficient alternative to syringe pass-through, and the filtering of HuNoV stool suspensions could be avoided. Moreover, comparable replication yields of clinical strains of HuNoV genogroup I (GI), HuNoV GII, rotavirus (RV), astrovirus (HAstV), and adenoviruses (HAdV) were obtained in single and multiple co-infections. Then, the optimized HIE model was used to demonstrate the infectivity of multiple naturally occurring gastroenteritis viruses from wastewater. Thus, a total of 28 wastewater samples were subjected to (RT)-qPCR for each virus, with subsequent testing on HIE. Among these, 16 samples (57 %) showed replication of HuNoVs (n = 3), RV (n = 5), HAstV (n = 8), and/or HAdV (n = 5). Three samples showed HuNoV replication, and sequences assigned to HuNoV GI.3[P13] and HuNoV GII.4[P16] genotypes. Concurrent replication of multiple gastroenteritis viruses occurred in 4 wastewater samples. By comparing wastewater concentrate and HIE supernatant sequences, diverse HAstV and HAdV genotypes were identified in 4 samples. In summary, we successfully employed HIE to demonstrate the presence of multiple infectious human gastroenteritis viruses, including HuNoV, in naturally contaminated wastewater samples. |
Heat inactivation of aqueous viable norovirus and MS2 bacteriophage
Shaffer M , Huynh K , Costantini V , Vinjé J , Bibby K . J Appl Microbiol 2024 AIMS: This study aimed to compare the heat inactivation kinetics of viable human norovirus with the surrogate, MS2 bacteriophage as well as assess the decay of the RNA signal. METHODS AND RESULTS: Human intestinal enteroids (HIEs) were used to analyze the heat inactivation kinetics of viable human norovirus compared to the surrogate MS2 bacteriophage, which was cultured using a plaque assay. Norovirus decay rates were 0.22 min-1, 0.68 min-1, and 1.11 min-1 for 50°C, 60°C, and 70°C, respectively, and MS2 bacteriophage decay rates were 0.0065 min-1, 0.045 min-1, and 0.16 min-1 for 50°C, 60°C, and 70°C, respectively. Norovirus had significantly higher decay rates than MS2 bacteriophage at all tested temperatures (P = 0.002-0.007). No decrease of RNA titers as measured by reverse transcription-PCR for both human norovirus and MS2 bacteriophage over time was observed, indicating molecular methods do not accurately depict viable human norovirus after heat inactivation and treatment efficiency is underestimated. CONCLUSIONS: Overall, our data demonstrates that MS2 bacteriophage is a conservative surrogate to measure heat inactivation and potentially overestimates the infectious risk of norovirus. Furthermore, this study corroborates that measuring viral RNA titers, as evaluated by PCR methods, does not correlate with the persistence of viable norovirus under heat inactivation. |
Multicenter evaluation of BioCode GPP for syndromic molecular detection of gastrointestinal pathogens from stool specimens
Knoth C , Humphries R , Johnson JK , Patel A , Lima A , Silbert S , Vinjé J . J Clin Microbiol 2024 e0154523 Acute gastroenteritis (AGE) is a leading cause of morbidity and mortality worldwide across all age groups that disproportionally affects young children in low- and middle-income countries and immunocompromised patients in high-income countries. Regional outbreaks of AGE are typically detected by traditional microbiological detection methods that target limited organisms and are associated with low sensitivity and lengthy time-to-results. Combined, these may result in repeat testing, imprecise or delayed treatment, and delayed recognition of outbreaks. We conducted a multi-site prospective study comparing the BioCode Gastrointestinal Pathogen Panel (BioCode GPP) for the detection of 17 common bacterial, viral, and protozoan causes of gastroenteritis with reference methods, including stool culture, enzyme immunoassays, pathogen-specific PCR assays, and sequencing. One thousand five hundred fifty-eight residual, de-identified stool samples (unpreserved stool and stool in Cary-Blair transport medium) were enrolled and tested for 11 bacterial, 3 viral, and 3 protozoan pathogens. BioCode GPP and reference methods were positive for 392 (25.2%) and 283 (18.2%) samples, respectively (P < 0.0001). In this study, the BioCode GPP and reference methods detected 69 and 65 specimens positive for Clostridioides difficile, 51 and 48 for enteroaggregative Escherichia coli, 33 and 27 for enterotoxigenic E. coli, 50 and 47 for norovirus GI/GII, and 30 and 22 for rotavirus A, respectively. The BioCode GPP showed good positive and negative agreements for each pathogen ranging from 89.5% to 100%, with overall sensitivity and specificity of 96.1% and 99.7%, post adjudication. The BioCode GPP detected >1 pathogens in 49 samples, representing 12.5% of the total 392 positive specimens.IMPORTANCEThis study highlights performance of a novel technology for timely and accurate detection and differentiation of 17 common bacterial, viral, and protozoan causes of gastroenteritis. Utilizing molecular tests such as the BioCode Gastrointestinal Pathogen Panel may improve the detection of gastrointestinal pathogens and provide actionable results, particularly for patient populations at most risk. |
A diverse group of small circular ssDNA viral genomes in human and non-human primate stools.
Ng TF , Zhang W , Sachsenröder J , Kondov NO , da Costa AC , Vega E , Holtz LR , Wu G , Wang D , Stine CO , Antonio M , Mulvaney US , Muench MO , Deng X , Ambert-Balay K , Pothier P , Vinjé J , Delwart E . Virus Evol 2015 1 (1) vev017 Viral metagenomics sequencing of fecal samples from outbreaks of acute gastroenteritis from the US revealed the presence of small circular ssDNA viral genomes encoding a replication initiator protein (Rep). Viral genomes were ∼2.5 kb in length, with bi-directionally oriented Rep and capsid (Cap) encoding genes and a stem loop structure downstream of Rep. Several genomes showed evidence of recombination. By digital screening of an in-house virome database (1.04 billion reads) using BLAST, we identified closely related sequences from cases of unexplained diarrhea in France. Deep sequencing and PCR detected such genomes in 7 of 25 US (28 percent) and 14 of 21 French outbreaks (67 percent). One of eighty-five sporadic diarrhea cases in the Gambia was positive by PCR. Twenty-two complete genomes were characterized showing that viruses from patients in the same outbreaks were closely related suggesting common origins. Similar genomes were also characterized from the stools of captive chimpanzees, a gorilla, a black howler monkey, and a lemur that were more diverse than the human stool-associated genomes. The name smacovirus is proposed for this monophyletic viral clade. Possible tropism include mammalian enteric cells or ingested food components such as infected plants. No evidence of viral amplification was found in immunodeficient mice orally inoculated with smacovirus-positive stool supernatants. A role for smacoviruses in diarrhea, if any, remains to be demonstrated. |
Hospital-based norovirus surveillance in children <5 years of age from 2017 to 2019 in India
Giri S , Chhabra P , Kulkarni R , Reju S , Sabapathy SK , Selvarajan S , Varghese T , Kalaivanan M , Dorairaj P , Kalrao V , Mankar S , Sangamnerkar M , Chethrapilly Purushothaman GK , Srikanth P , Kang G , Vinjé J . J Med Virol 2024 96 (1) e29384 After the introduction of the rotavirus vaccine into the Universal Immunization Program in India in 2016, relatively few studies have assessed the prevalence and epidemiological patterns of acute gastroenteritis (AGE) among hospitalized children ≤5 years of age. We used a uniform protocol to recruit children with AGE as well as standardized testing and typing protocols. Stool specimens from children with AGE younger than 5 years of age admitted to six hospitals in three cities in India were collected from January 2017 through December 2019. Norovirus was detected by real-time reverse transcription-polymerase chain reaction (RT-qPCR) followed by typing positive specimens by conventional RT-PCR and Sanger sequencing. Norovirus was detected in 322 (14.8%) of 2182 specimens with the highest rate in 2018 (17.6%, 146/829), followed by 2019 (14.4%, 122/849) and 2017 (10.7%, 54/504). Rotavirus vaccine status was known for 91.6% of the children of which 70.4% were vaccinated and 29.6% not. Norovirus positivity in rotavirus-vaccinated children was 16.3% and 12% in unvaccinated children. GII.4 Sydney[P16] (39.3%), GII.4 Sydney[P31] (18.7%), GII.2[P16] (10%), GI.3[P13] (6.8%), GII.3[P16] (5.9%), and GII.13[P16] (5%) accounted for 85.8% (188/219) of the typed strains. Our data highlight the importance of norovirus in Indian children hospitalized with AGE. |
Emergence of novel norovirus GII.4 variant
Chhabra P , Tully DC , Mans J , Niendorf S , Barclay L , Cannon JL , Montmayeur AM , Pan CY , Page N , Williams R , Tutill H , Roy S , Celma C , Beard S , Mallory ML , Manouana GP , Velavan TP , Adegnika AA , Kremsner PG , Lindesmith LC , Hué S , Baric RS , Breuer J , Vinjé J . Emerg Infect Dis 2024 30 (1) 163-167 We detected a novel GII.4 variant with an amino acid insertion at the start of epitope A in viral protein 1 of noroviruses from the United States, Gabon, South Africa, and the United Kingdom collected during 2017-2022. Early identification of GII.4 variants is crucial for assessing pandemic potential and informing vaccine development. |
Vaccine value profile for norovirus
Armah G , Lopman BA , Vinjé J , O'Ryan M , Lanata CF , Groome M , Ovitt J , Marshall C , Sajewski E , Riddle MS . Vaccine 2023 41 Suppl 2 S134-S152 Norovirus is attributed to nearly 1 out of every 5 episodes of diarrheal disease globally and is estimated to cause approximately 200,000 deaths annually worldwide, with 70,000 or more among children in developing countries. Noroviruses remain a leading cause of sporadic disease and outbreaks of acute gastroenteritis even in industrialized settings, highlighting that improved hygiene and sanitation alone may not be fully effective in controlling norovirus. Strengths in global progress towards a Norovirus vaccine include a diverse though not deep pipeline which includes multiple approaches, including some with proven technology platforms (e.g., VLP-based HPV vaccines). However, several gaps in knowledge persist, including a fulsome mechanistic understanding of how the virus attaches to human host cells, internalizes, and induces disease. © 2023 The Author(s) |
Epidemiology and risk factors of norovirus infections among diarrhea patients admitted to tertiary care hospitals in Bangladesh
Satter SM , Abdullah Z , Fariha F , Karim Y , Rahman MM , Balachandran N , Ghosh PK , Hossain ME , Mirza SA , Hall AJ , Gastañaduy PA , Rahman M , Vinjé J , Parashar UD . J Infect Dis 2023 228 (7) 818-828 BACKGROUND: Norovirus is a major cause of endemic acute gastroenteritis (AGE) worldwide. We described the epidemiology, risk factors, and genotypic distribution of noroviruses among hospitalized patients of all ages in Bangladesh. METHODS: From March 2018 to October 2021, 1250 AGE case patients and controls (age, sex, season, and site matched) were enrolled at 10 hospitals. Demographic and clinical information was collected; real-time reverse-transcriptase polymerase chain reaction (RT-PCR) used to test stool specimens, and positive samples were genotyped. RESULTS: Norovirus was detected in 9% of cases (111 of 1250) and 15% (182 of 1250) of controls. Eighty-two percent of norovirus-positive cases were in children <5 years old. Norovirus-positive AGE hospitalizations occurred year-round, with peaks in April and October. Risk factors for norovirus included age <5 years (adjusted odds ratio, 3.1 [95% confidence interval, 1.9-5.2]) and exposure to a patient with AGE in the 10 days before enrollment (3.8 [1.9-7.2]). GII.3[P16] and GII.4 Sydney[P16] were the predominant genotypes. CONCLUSIONS: We highlight the burden of norovirus in hospital settings. Young age and recent exposure to a patient with AGE were risk factors for norovirus. A high prevalence of norovirus among controls might represent asymptomatic reinfections or prolonged shedding from a previous infection; carefully designed longitudinal studies are needed to improve our understanding of norovirus infections in Bangladesh. |
Paediatric acute hepatitis of unknown aetiology: a national surveillance investigation in the USA during 2021 and 2022
Cates J , Baker JM , Almendares O , Balachandran N , McKeever ER , Kambhampati AK , Cubenas C , Vinjé J , Cannon JL , Chhabra P , Freeman B , Reagan-Steiner S , Bhatnagar J , Gastañaduy PA , Kirking HL , Sugerman D , Parashar UD , Tate JE . Lancet Child Adolesc Health 2023 7 (11) 773-785 BACKGROUND: Adenovirus is a known cause of hepatitis in immunocompromised children, but not in immunocompetent children. In April, 2022, following multiple reports of hepatitis of unknown aetiology and adenovirus viraemia in immunocompetent children in the USA and UK, the US Centers for Disease Control and Prevention (CDC) and jurisdictional health departments initiated national surveillance of paediatric acute hepatitis of unknown aetiology. We aimed to describe the clinical and epidemiological characteristics of children identified with hepatitis of unknown aetiology between Oct 1, 2021, and Sept 30, 2022, in the USA and to compare characteristics of those who tested positive for adenovirus with those who tested negative. METHODS: In this national surveillance investigation in the USA, children were identified for investigation if they were younger than 10 years with elevated liver transaminases (>500 U/L) who had an unknown cause for their hepatitis and onset on or after Oct 1, 2021. We reviewed medical chart abstractions, which included data on demographics, underlying health conditions, signs and symptoms of illness, laboratory results, vaccination history, radiological and liver pathology findings, diagnoses and treatment received, and outcomes. Caregiver interviews were done to obtain information on symptoms and health-care utilisation for the hepatitis illness, medical history, illness in close contacts or at school or daycare, diet, travel, and other potential exposures. Blood, stool, respiratory, and tissue specimens were evaluated according to clinician discretion and available specimens were submitted to CDC for additional laboratory testing or pathology evaluation. FINDINGS: Surveillance identified 377 patients from 45 US jurisdictions with hepatitis of unknown aetiology with onset from Oct 1, 2021, to Sept 30, 2022. The median age of patients was 2·8 years (IQR 1·2-5·0) and 192 (51%) were male, 184 (49%) were female, and one patient had sex unknown. Only 22 (6%) patients had a notable predisposing underlying condition. 347 patients (92%) were admitted to hospital, 21 (6%) subsequently received a liver transplant, and nine (2%) died. Among the 318 patients without notable underlying conditions, 275 were tested for adenovirus. Of these 116 (42%) had at least one positive specimen, and species F type 41 was the most frequent type identified (19 [73%] of 26 typed specimens were HAdV-41). Proportions of patients who had acute liver failure, received a liver transplant, and died were similar between those who tested positive for adenovirus compared with those who tested negative. Adenovirus species F was detected by polymerase chain reaction in nine pathology liver evaluations, but not by immunohistochemistry in seven of the nine with adequate liver tissue available. Interviews with caregivers yielded no common exposures. INTERPRETATION: Adenovirus, alone or in combination with other factors, might play a potential role in acute hepatitis among immunocompetent children identified in this investigation, but the pathophysiologic mechanism of liver injury is unclear. To inform both prevention and intervention measures, more research is warranted to determine if and how adenovirus might contribute to hepatitis risk and the potential roles of other pathogens and host factors. FUNDING: None. |
SARS-CoV-2 surface contamination in metro-Atlanta grocery stores
Brown TW , Park GW , Wittry B , Barclay L , Person M , Relja B , Daly S , Chhabra P , Kincaid E , Johnson J , Ahmad A , Herzegh O , Vinjé J , Murphy J . PLoS One 2023 18 (9) e0291747 While the COVID-19 pandemic has had a detrimental impact on many businesses worldwide, essential businesses, such as grocery stores, continued to operate despite potential disease transmission. Although the principal mode by which people are infected with SARS-CoV-2, the virus that causes COVID-19, is through exposure to respiratory droplets and very small particles carrying infectious virus, contaminated surfaces might play a role in transmission. We collected swab samples from frequently touched surfaces, including grocery carts, touchscreen monitors, credit card keypads, pharmacy counters, self-service food utensils, and refrigerator and freezer handles, in two metro-Atlanta grocery stores over the course of two sampling events in March 2021. Of the 260 swab samples collected, 6 (2.3%) samples were positive for SARS-CoV-2 RNA by reverse transcriptase quantitative polymerase chain reaction. Positive samples were collected from pharmacy (12.0% [3/25] samples), refrigerator/freezer aisles (2.5% [1/39] samples), and self-service food court (5.0% [2/40] samples) areas. Table/counter edge and underside surfaces represented 33% (2/6) of positive samples. These data suggest that risk of exposure to SARS-CoV-2 from frequently touched surfaces in grocery store settings is likely low; however, more frequent cleaning of surfaces in pharmacy and self-service food courts might be warranted. |
Infant antibody and B-cell responses following confirmed pediatric GII.17 norovirus infections functionally distinguish GII.17 genetic clusters
Strother CA , Brewer-Jensen PD , Becker-Dreps S , Zepeda O , May S , Gonzalez F , Reyes Y , McElvany BD , Averill AM , Mallory ML , Montmayeur AM , Costantini VP , Vinjé J , Baric RS , Bucardo F , Lindesmith LC , Diehl SA . Front Immunol 2023 14 1229724 Genogroup II (GII) noroviruses are a major cause of diarrheal disease burden in children in both high- and low-income countries. GII.17 noroviruses are composed of distinct genetic clusters (I, II, IIIa, and IIIb) and have shown potential for replacing historically more prevalent GII.4 strains, but the serological basis for GII.17 antigenic diversity has not been studied in children. Utilizing samples from a birth cohort, we investigated antibody and B-cell responses to GII.17 cluster variants in confirmed GII.17 infections in young children as well as demonstrated that the distinct genetic clusters co-circulate. Polyclonal serum antibodies bound multiple clusters but showed cluster-specific blockade activity in a surrogate virus neutralization assay. Antibodies secreted by immortalized memory B cells (MBCs) from an infant GII.17 case were highly specific to GII.17 and exhibited blockade activity against this genotype. We isolated an MBC-derived GII.17-specific Immunoglobulin A (IgA) monoclonal antibody called NVA.1 that potently and selectively blocked GII.17 cluster IIIb and recognized an epitope targeted in serum from cluster IIIb-infected children. These data indicate that multiple antigenically distinct GII.17 variants co-circulate in young children, suggesting retention of cluster diversity alongside potential for immune escape given the existence of antibody-defined cluster-specific epitopes elicited during infection. |
Preadaptation of pandemic GII.4 noroviruses in hidden virus reservoirs years before emergence (preprint)
Ruis C , Lindesmith LC , Mallory ML , Brewer-Jensen PD , Bryant JM , Costantini V , Monit C , Vinjé J , Baric RS , Goldstein RA , Breuer J . bioRxiv 2019 658765 The control of pandemic pathogens depends on early prediction of pandemic variants and, more generally, understanding origins of such variants and factors that drive their global spread. This is especially important for GII.4 norovirus, where vaccines under development offer promise to prevent hundreds of millions of annual gastroenteritis cases. Previous studies have suggested that new GII.4 pandemic viruses evolve from previous pandemic variants through substitutions in the antigenic region of the VP1 protein that enable evasion of host population immunity, leading to global spread. In contrast, we show here that the acquisition of new genetic and antigenic characteristics is not the proximal driver of new pandemics. Instead, pandemic GII.4 viruses circulate undetected for years before causing a new pandemic, during which time they diversify and spread over wide geographical areas. Serological data demonstrate that by 2003, some nine years before it emerged as a new pandemic, the ancestral 2012 pandemic strain had already acquired the antigenic characteristics that allowed it to evade prevailing population immunity against the previous 2009 pandemic variant. These results provide strong evidence that viral genetic changes are necessary but not sufficient for GII.4 pandemic spread. Instead, we suggest that it is changes in host population immunity that enable pandemic spread of an antigenically-preadapted GII.4 variant. These results indicate that predicting future GII.4 pandemic variants will require surveillance of currently unsampled reservoir populations. Furthermore, a broadly acting GII.4 vaccine will be critical to prevent future pandemics.Significance Norovirus pandemics and their associated public health and economic costs could be prevented by effective vaccines. However, vaccine development and distribution will require identification of the sources and drivers of new pandemics. We here use phylogenetics and serological experiments to develop and test a new hypothesis of pandemic norovirus emergence. We find that pandemic noroviruses preadapt, diversify and spread worldwide years prior to emergence, strongly indicating that genetic changes are necessary but not sufficient to drive a new pandemic. We instead suggest that changes in population immunity enable pandemic emergence of a pre-adapted low-level variant. These findings indicate that prediction of new pandemics will require surveillance of under-sampled virus reservoirs and that norovirus vaccines will need to elicit broad immunity. |
Enteropathogen antibody dynamics and force of infection among children in low-resource settings (preprint)
Arnold BF , Martin DL , Juma J , Mkocha H , Ochieng JB , Cooley GM , Omore R , Goodhew EB , Morris JF , Costantini V , Vinje J , Lammie PJ , Priest JW . bioRxiv 2019 522920 Little is known about enteropathogen seroepidemiology among children in low-resource settings. We measured serological IgG responses to eight enteropathogens (Giardia intestinalis, Cryptosporidium parvum, Entamoeba histolytica, Salmonella enterica, enterotoxigenic Escherichia coli, Vibrio cholerae, Campylobacter jejuni, norovirus) in cohorts from Haiti, Kenya, and Tanzania. We studied antibody dynamics and force of infection across pathogens and cohorts. Enteropathogens shared common seroepidemiologic features that enabled between-pathogen comparisons of transmission. Overall, exposure was intense: for most pathogens the window of primary infection was <3 years old; for highest transmission pathogens primary infection occurred within the first year. Longitudinal profiles revealed significant IgG boosting and waning above seropositivity cutoffs, underscoring the value of longitudinal designs to estimate force of infection. Seroprevalence and force of infection were rank-preserving across pathogens, illustrating the measures provide similar information about transmission heterogeneity. Our findings suggest multiplex antibody assays are a promising approach to measure population-level enteropathogen transmission in serologic surveillance. |
Comparison of Illumina MiSeq and the Ion Torrent PGM and S5 platforms for whole-genome sequencing of picornaviruses and caliciviruses (preprint)
Marine RL , Magana LC , Castro CJ , Zhao K , Montmayeur AM , Schmidt A , Diez-Valcarce M , Fan Ng TF , Vinje J , Burns CC , Allan Nix W , Rota PA , Oberste MS . bioRxiv 2019 705632 Next-generation sequencing is a powerful tool for virological surveillance. While Illumina® and Ion Torrent® sequencing platforms are used extensively for generating viral RNA genome sequences, there is limited data comparing different platforms. We evaluated the Illumina MiSeq, Ion Torrent PGM and Ion Torrent S5 platforms using a panel of sixteen specimens containing picornaviruses and human caliciviruses (noroviruses and sapoviruses). The specimens were processed, using combinations of three library preparation and five sequencing kits, to assess the quality and completeness of assembled viral genomes, and an estimation of cost per sample to generate the data was calculated. The choice of library preparation kit and sequencing platform was found to impact the breadth of genome coverage and accuracy of consensus viral genomes. The Ion Torrent S5 outperformed the older Ion Torrent PGM platform in data quality and cost, and generated the highest proportion of reads for enterovirus D68 samples. However, indels at homopolymer regions impacted the accuracy of consensus genome sequences. For lower throughput sequencing runs (i.e., Ion Torrent 510 or Illumina MiSeq Nano V2), the cost per sample was lower on the MiSeq platform, whereas with higher throughput runs (Ion Torrent 530 or Illumina MiSeq V2) the cost per sample was comparable. These findings suggest that the Ion Torrent S5 and Illumina MiSeq platforms are both viable options for genomic sequencing of RNA viruses, each with specific advantages and tradeoffs. |
Mucosal and systemic neutralizing antibodies to norovirus and rotavirus by oral immunization with recombinant rotavirus in infant mice (preprint)
Kawagishi T , Sanchez-Tacuba L , Feng N , Costantini VP , Tan M , Jiang X , Green KY , Vinje J , Ding S , Greenberg HB . bioRxiv 2022 02 Rotaviruses (RVs) preferentially replicate in the small intestine, frequently cause severe diarrheal disease, and following enteric infection generally induce variable levels of protective systemic and mucosal immune responses in humans and other animals. Rhesus rotavirus (RRV) is a simian RV that was previously used as a human RV vaccine and has been extensively studied in mice. Although RRV replicates poorly in the suckling mouse intestine, infection induces a robust and protective antibody response. The recent availability of plasmid-based RV reverse genetics systems has enabled the generation of recombinant RVs expressing foreign proteins. However, recombinant RVs have not yet been experimentally tested as potential vaccine vectors to immunize against other gastrointestinal pathogens in vivo. This is a missed opportunity because several live-attenuated RV vaccines are already widely administered to infants and young children worldwide. To explore the feasibility of using RV as a dual vaccine vector, we rescued a replication-competent recombinant RRV harboring bicistronic gene segment 7 that encodes both the native RV NSP3 protein and a human norovirus (HuNoV) VP1 protein from the predominant genotype GII.4 (rRRV-HuNoV-VP1). The rRRV-HuNoV-VP1 expressed HuNoV VP1 in infected cells in vitro and importantly, elicited both systemic and local antibody responses to HuNoV following oral infection of suckling mice. Serum IgG and fecal IgA from infected suckling mice bound to and neutralized both RV and HuNoV. These findings have encouraging practical implications for the design of RV-based next-generation multivalent enteric vaccines to target HuNoV and other human enteric pathogens while providing immunity to RV. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Development and validation of an enzyme immunoassay for detection and quantification of SARS-CoV-2 salivary IgA and IgG (preprint)
Costantini VP , Nguyen K , Lyski Z , Novosad S , Bardossy AC , Lyons AK , Gable P , Kutty PK , Lutgring JD , Brunton A , Thornburg NJ , Brown AC , McDonald LC , Messer W , Vinjé J . medRxiv 2021 Oral fluids offer a non-invasive sampling method for the detection of antibodies. Quantification of IgA and IgG antibodies in saliva allows studies of the mucosal and systemic immune response after natural infection or vaccination. We developed and validated an enzyme immunoassay (EIA) to detect and quantify salivary IgA and IgG antibodies against the prefusion-stabilized form of the SARS-CoV-2 spike protein. Normalization against total antibody isotype was performed to account for specimen differences, such as collection time and sample volume. Saliva samples collected from 187 SARS-CoV-2 confirmed cases enrolled in 2 cohorts and 373 pre-pandemic saliva samples were tested. The sensitivity of both EIAs was high (IgA: 95.5%; IgG: 89.7%) without compromising specificity (IgA: 99%; IgG: 97%). No cross reactivity with seasonal coronaviruses was observed. The limit of detection for SARS-CoV-2 salivary IgA and IgG assays were 1.98 ng/mL and 0.30 ng/mL, respectively. Salivary IgA and IgG antibodies were detected earlier in patients with mild COVID-19 symptoms than in severe cases. However, severe cases showed higher salivary antibody titers than those with a mild infection. Salivary IgA titers quickly decreased after 6 weeks in mild cases but remained detectable until at least week 10 in severe cases. Salivary IgG titers remained high for all patients, regardless of disease severity. In conclusion, EIAs for both IgA and IgG had high specificity and sensitivity for the confirmation of current or recent SARS-CoV-2 infections and evaluation of the IgA and IgG immune response. |
Norovirus Outbreak Surveillance, China, 2016-2018
Jin M , Wu S , Kong X , Xie H , Fu J , He Y , Feng W , Liu N , Li J , Rainey JJ , Hall AJ , Vinjé J , Duan Z . Emerg Infect Dis 2020 26 (3) 437-445 CaliciNet China, a network of provincial, county, and city laboratories coordinated by the Chinese Centers for Disease Control and Prevention, was launched in October 2016 to monitor the epidemiology and genotype distribution of norovirus outbreaks in China. During October 2016-September 2018, a total of 556 norovirus outbreaks were reported, and positive fecal samples from 470 (84.5%) outbreaks were genotyped. Most of these outbreaks were associated with person-to-person transmission (95.1%), occurred in childcare centers or schools (78.2%), and were reported during November-March of each year (63.5%). During the 2-year study period, 81.2% of all norovirus outbreaks were typed as GII.2[P16]. In China, most norovirus outbreaks are reported by childcare centers or schools; GII.2[P16] is the predominant genotype. Ongoing surveillance by CaliciNet China will provide information about the evolving norovirus genotype distribution and outbreak characteristics important for the development of effective interventions, including vaccines. |
Adeno-associated virus type 2 in US children with acute severe hepatitis.
Servellita V , Gonzalez AS , Lamson DM , Foresythe A , Huh HJ , Bazinet AL , Bergman NH , Bull RL , Garcia KY , Goodrich JS , Lovett SP , Parker K , Radune D , Hatada A , Pan CY , Rizzo K , Bertumen JB , Morales C , Oluniyi PE , Nguyen J , Tan J , Stryke D , Jaber R , Leslie MT , Lyons Z , Hedman HD , Parashar U , Sullivan M , Wroblewski K , Oberste MS , Tate JE , Baker JM , Sugerman D , Potts C , Lu X , Chhabra P , Pediatric Hepatitis of Unknown Etiology Working Group , Ingram LA , Shiau H , Britt W , Sanchez LHG , Ciric C , Rostad CA , Vinjé J , Kirking HL , Wadford DA , Raborn RT , St George K , Chiu CY . Nature 2023 As of August 2022, clusters of acute severe hepatitis of unknown etiology in children have been reported from 35 countries, including the United States(1,2). Previous studies have found human adenoviruses (HAdVs) in the blood from cases in Europe and the United States(3-7), although it is unclear whether this virus is causative. Here we used PCR testing, viral enrichment based sequencing, and agnostic metagenomic sequencing to analyze samples from 16 HAdV-positive cases from October 1, 2021 to May 22, 2022, in parallel with 113 controls. In blood from 14 cases, adeno-associated virus 2 (AAV2) sequences were detected in 93% (13 of 14), compared to 4 (3.5%) of 113 controls (P<0.001) and to 0 of 30 patients with hepatitis of defined etiology (P<0.001). In controls, HAdV-41 was detected in blood from 9 (39.1%) of the 23 patients with acute gastroenteritis (without hepatitis), including 8 of 9 patients with positive stool HAdV testing, but co-infection with AAV2 was observed in only 3 (13.0%) of these 23 patients versus 93% of cases (P<0.001). Co-infections by Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), and/or enterovirus A71 (EV-A71) were also detected in 12 (85.7%) of 14 cases, with higher herpesvirus detection in cases versus controls (P<0.001). Our findings suggest that the severity of the disease is related to co-infections involving AAV2 and one or more helper viruses. |
Corrigendum: Updated classification of norovirus genogroups and genotypes.
Chhabra P , Graaf M , Parra GI , Chan MC , Green K , Martella V , Wang Q , White PA , Katayama K , Vennema H , Koopmans MPG , Vinjé J . J Gen Virol 2020 101 (8) 893 The genotypes referred to in this article were stated incorrectly. The genotype number 49 should have been stated as 48 and the number 27 should have been stated as 26. These errors occurred in the 'Abstract' section on page 1, in the ‘Discussion’ section on page 11, and within Fig. 5 on page 12. | | The sentence in the 'Abstract' should have read: | | ‘Using previously described 2× standard deviation (sd) criteria to group sequences into separate clusters, we expanded the number of genogroups to 10 (GI-GX) and the number of genotypes to 48 (9 GI, 26 GII, 3 GIII, 2 GIV, 2 GV, 2 GVI and 1 genotype each for GVII, GVIII, GIX [formerly GII.15] and GX).’ | | The sentence in the 'Discussion' section on page 11 should have read: | | ‘Viruses in these ten genogroups can be further divided into 48 confirmed capsid genotypes based on amino acids of the complete VP1 and 60 confirmed P-types based on partial nucleotide sequences of RdRp regions.’ | | Fig. 5 on page 12 erroneously stated ‘27+2T’. This should have been stated as ‘26+2T’. |
Household Surveillance for Norovirus Gastroenteritis in a Nicaraguan Birth Cohort: A Nested Case-Control Analysis of Norovirus Risk Factors.
Vielot NA , Zepeda O , Reyes Y , González F , Vinjé J , Becker-Dreps S , Bucardo F . Pathogens 2023 12 (3) Norovirus causes a large proportion of pediatric acute gastroenteritis (AGE) worldwide, and no vaccines are currently available. To inform public health measures against norovirus gastroenteritis, we assessed risk factors in a case-control study nested in a birth cohort study in Nicaragua. Between June 2017 and January 2022, we followed children weekly for AGE episodes, and collected stool specimens from symptomatic children. Risk factors for AGE were collected during routine weekly visits. Norovirus was detected in stools using real-time reverse transcriptase polymerase chain reaction and positive specimens were genotyped using Sanger sequencing. We included 40 norovirus-positive AGE children matched 1:2 to controls and conducted bivariate and multivariable analyses of norovirus AGE risk factors. Among typeable norovirus infections, GII.4 were more severe than non-GII.4 (four/twenty-one vs. one/nine) and accounted for all emergency visits and hospitalizations. Adjusted conditional logistic regression found that female sex and higher length-for-age Z score were protective against norovirus AGE; a dirt floor in the home, sharing cups or bottles, and recent contact with someone with AGE symptoms were associated with norovirus AGE, though estimates were highly imprecise. Reducing contact with symptomatic persons and with saliva or other bodily fluids on cups or floors could reduce infant norovirus incidence. |
Mucosal and systemic neutralizing antibodies to norovirus induced in infant mice orally inoculated with recombinant rotaviruses.
Kawagishi T , Sánchez-Tacuba L , Feng N , Costantini VP , Tan M , Jiang X , Green KY , Vinjé J , Ding S , Greenberg HB . Proc Natl Acad Sci U S A 2023 120 (9) e2214421120 Rotaviruses (RVs) preferentially replicate in the small intestine and frequently cause severe diarrheal disease, and the following enteric infection generally induces variable levels of protective systemic and mucosal immune responses in humans and other animals. Rhesus rotavirus (RRV) is a simian RV that was previously used as a human RV vaccine and has been extensively studied in mice. Although RRV replicates poorly in the suckling mouse intestine, infection induces a robust and protective antibody response. The recent availability of plasmid only-based RV reverse genetics systems has enabled the generation of recombinant RVs expressing foreign proteins. However, recombinant RVs have not yet been experimentally tested as potential vaccine vectors to immunize against other gastrointestinal pathogens in vivo. This is a newly available opportunity because several live-attenuated RV vaccines are already widely administered to infants and young children worldwide. To explore the feasibility of using RV as a dual vaccine vector, we rescued replication-competent recombinant RRVs harboring bicistronic gene segment 7 that encodes the native RV nonstructural protein 3 (NSP3) protein and a human norovirus (HuNoV) VP1 protein or P domain from the predominant genotype GII.4. The rescued viruses expressed HuNoV VP1 or P protein in infected cells in vitro and elicited systemic and local antibody responses to HuNoV and RRV following oral infection of suckling mice. Serum IgG and fecal IgA from infected suckling mice bound to and neutralized both RRV and HuNoV. These findings have encouraging practical implications for the design of RV-based next-generation multivalent enteric vaccines to target HuNoV and other human enteric pathogens. |
Persistence of Human Norovirus (GII) in Surface Water: Decay Rate Constants and Inactivation Mechanisms.
Kennedy LC , Costantini VP , Huynh KA , Loeb SK , Jennings WC , Lowry S , Mattioli MC , Vinjé J , Boehm AB . Environ Sci Technol 2023 57 (9) 3671-3679 Human norovirus (HuNoV) is an important cause of acute gastroenteritis and can be transmitted by water exposures, but its persistence in water is not well understood. Loss of HuNoV infectivity in surface water was compared with persistence of intact HuNoV capsids and genome segments. Surface water from a freshwater creek was filter-sterilized, inoculated with HuNoV (GII.4) purified from stool, and incubated at 15 or 20 °C. We measured HuNoV infectivity via the human intestinal enteroid system and HuNoV persistence via reverse transcription-quantitative polymerase chain reaction assays without (genome segment persistence) or with (intact viral capsid persistence) enzymatic pretreatment to digest naked RNA. For infectious HuNoV, results ranged from no significant decay to a decay rate constant ("k") of 2.2 day(-1). In one creek water sample, genome damage was likely a dominant inactivation mechanism. In other samples from the same creek, loss of HuNoV infectivity could not be attributed to genome damage or capsid cleavage. The range in k and the difference in the inactivation mechanism observed in water from the same site could not be explained, but variable constituents in the environmental matrix could have contributed. Thus, a single k may be insufficient for modeling virus inactivation in surface waters. |
Timing and genotype distribution of symptomatic and asymptomatic sapovirus infections and re-infections in a Nicaraguan birth cohort.
González F , Diez-Valcarce M , Reyes Y , Vielot NA , Toval C , Gutiérrez L , Zepeda O , Cuadra EC , Blandón P , Browne H , Bowman NM , Víchez S , Vinjé J , Becker-Dreps S , Bucardo F . Clin Microbiol Infect 2022 29 (4) 540 e9-540 e15 OBJECTIVES: To characterize the timing and genotype distribution of symptomatic and asymptomatic sapovirus infections and re-infections in a Nicaraguan birth cohort. METHODS: Infants (n = 444) were enrolled at 10-14 days of life and followed weekly until 2 years of age. Stool were collected for each acute gastroenteritis (AGE) episode and routine stool were collected monthly. Stools were tested for sapovirus by RT-qPCR and positive samples were genotyped. RESULTS: A total of 348 children completes 2 years of AGE weekly surveillance, 93 (26.7%) of them experienced sapovirus AGE. Most infections occurred after 5 months of age and mainly the second year of life (62.4%, 58/93) and early in the rainy season. Sapovirus screening in all stools from a subset of 67 children, that consistently provided samples, show sapovirus infections in 27.6% (91/330) of the AGE episode and in 2.9% (39/1350) of the routine stool. In this subset, the median age at the first sapovirus AGE was 11.2 month (95%CI; 9.3 - 15.9), 57% (38/67) experienced re-infections, 19 symptomatic and 19 asymptomatic; on average, sapovirus re-infections were reported 7.2 months after symptomatic and 5.3 after asymptomatic infections. Genogroups GI (64%, 69/108) was the most common detected. Sapovirus GI.1 was more frequently detected in AGE than in routine stools (47.2%, 43/91 vs 25.6%, 10/39; p = 0.005) and re-infection with the same genotype was uncommon. CONCLUSION: The first sapovirus infections occurred around 11 months of age, whereas the median time to symptomatic re-infection was 7.2 months. Re-infections with the same sapovirus genotype were rare during 2 years of life suggesting genotype-specific protection following natural infection. |
Viable norovirus persistence in water microcosms
Shaffer M , Huynh K , Costantini V , Bibby K , Vinjé J . Environ Sci Technol Lett 2022 9 (10) 851-855 Human noroviruses are one of the leading causes of acute gastroenteritis worldwide. Based on quantitative microbial risk assessments, norovirus contributes the greatest infectious risk of any pathogen from exposure to sewage-contaminated water; however, these estimates have been based upon molecular (i.e., RNA-based) data as human norovirus has remained largely unculturable in the laboratory. Current approaches to assess the environmental fate of noroviruses rely on the use of culturable surrogate viruses and molecular methods. Human intestinal enteroids (HIEs) are an emerging cell culture system capable of amplifying viable norovirus. Here, we applied the HIE assay to assess both viable norovirus and norovirus RNA persistence in surface, tap, and deionized water microcosms. Viable norovirus decreased to below the detection limit in tap and deionized water microcosms and was measured in a single replicate in the surface water microcosm at study conclusion (28 days). Conversely, the norovirus RNA signal remained constant over the duration of the study, even when viable norovirus was below the limit of detection. Our findings demonstrate the disconnect between current environmental norovirus detection via molecular methods and viability as assessed through the HIE assay. These results imply that molecular norovirus monitoring is not inherently representative of infectious norovirus. © 2022 American Chemical Society. |
Household characteristics associated with surface contamination of SARS-CoV-2 and frequency of RT-PCR and viral culture positivity-California and Colorado, 2021.
Shragai T , Pratt C , Castro Georgi J , Donnelly MAP , Schwartz NG , Soto R , Chuey M , Chu VT , Marcenac P , Park GW , Ahmad A , Albanese B , Totten SE , Austin B , Bunkley P , Cherney B , Dietrich EA , Figueroa E , Folster JM , Godino C , Herzegh O , Lindell K , Relja B , Sheldon SW , Tong S , Vinjé J , Thornburg NJ , Matanock AM , Hughes LJ , Stringer G , Hudziec M , Beatty ME , Tate JE , Kirking HL , Hsu CH . PLoS One 2022 17 (10) e0274946 While risk of fomite transmission of SARS-CoV-2 is considered low, there is limited environmental data within households. This January-April 2021 investigation describes frequency and types of surfaces positive for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) among residences with ≥1 SARS-CoV-2 infection, and associations of household characteristics with surface RT-PCR and viable virus positivity. Of 1232 samples from 124 households, 27.8% (n = 342) were RT-PCR positive with nightstands (44.1%) and pillows (40.9%) most frequently positive. SARS-CoV-2 lineage, documented household transmission, greater number of infected persons, shorter interval between illness onset and sampling, total household symptoms, proportion of infected persons ≤12 years old, and persons exhibiting upper respiratory symptoms or diarrhea were associated with more positive surfaces. Viable virus was isolated from 0.2% (n = 3 samples from one household) of all samples. This investigation suggests that while SARS-CoV-2 on surfaces is common, fomite transmission risk in households is low. |
Norovirus Infection in Young Nicaraguan Children Induces Durable and Genotype-Specific Antibody Immunity.
Brewer-Jensen PD , Reyes Y , Becker-Dreps S , González F , Mallory ML , Gutiérrez L , Zepeda O , Centeno E , Vielot N , Diez-Valcarce M , Vinjé J , Baric R , Lindesmith LC , Bucardo F . Viruses 2022 14 (9) There are significant challenges to the development of a pediatric norovirus vaccine, mainly due to the antigenic diversity among strains infecting young children. Characterizing human norovirus serotypes and understanding norovirus immunity in naïve children would provide key information for designing rational vaccine platforms. In this study, 26 Nicaraguan children experiencing their first norovirus acute gastroenteritis (AGE) episode during the first 18 months of life were investigated. We used a surrogate neutralization assay that measured antibodies blocking the binding of 13 different norovirus virus-like particles (VLPs) to histo-blood group antigens (HBGAs) in pre- and post-infection sera. To assess for asymptomatic norovirus infections, stools from asymptomatic children were collected monthly, screened for norovirus by RT-qPCR and genotyped by sequencing. Seroconversion of an HBGA-blocking antibody matched the infecting genotype in 25 (96%) of the 26 children. A subset of 13 (50%) and 4 (15%) of the 26 children experienced monotypic GII and GI seroconversion, respectively, strongly suggesting a type-specific response in naïve children, and 9 (35%) showed multitypic seroconversion. The most frequent pairing in multitypic seroconversion (8/12) were GII.4 Sydney and GII.12 noroviruses, both co-circulating at the time. Blocking antibody titers to these two genotypes did not correlate with each other, suggesting multiple exposure rather than cross-reactivity between genotypes. In addition, GII titers remained consistent for at least 19 months post-infection, demonstrating durable immunity. In conclusion, the first natural norovirus gastroenteritis episodes in these young children were dominated by a limited number of genotypes and induced responses of antibodies blocking binding of norovirus VLPs in a genotype-specific manner, suggesting that an effective pediatric norovirus vaccine likely needs to be multivalent and include globally dominant genotypes. The duration of protection from natural infections provides optimism for pediatric norovirus vaccines administered early in life. |
Notes from the field: Norovirus outbreaks reported through norostat - 12 states, August 2012-July 2022
Kambhampati AK , Wikswo ME , Barclay L , Vinjé J , Mirza SA . MMWR Morb Mortal Wkly Rep 2022 71 (38) 1222-1224 Norovirus is the leading cause of acute gastroenteritis in the United States (1). In April 2020, the incidence of norovirus outbreaks in the United States declined substantially, likely because of implementation of COVID-19–related nonpharmaceutical interventions, such as facility closures, social distancing, and increased hand hygiene (2). Similar declines were observed in other countries (3,4). Norovirus outbreaks in the United States increased rapidly starting in January 2022, approaching prepandemic (i.e., 2012–2019) levels. Norovirus transmission can be prevented by thorough handwashing and proper cleaning and disinfection of contaminated surfaces © 2022, MMWR Recommendations and Reports.All Rights Reserved. |
Immune Imprinting Drives Human Norovirus Potential for Global Spread.
Lindesmith LC , Boshier FAT , Brewer-Jensen PD , Roy S , Costantini V , Mallory ML , Zweigart M , May SR , Conrad H , O'Reilly KM , Kelly D , Celma CC , Beard S , Williams R , Tutill HJ , Becker Dreps S , Bucardo F , Allen DJ , Vinjé J , Goldstein RA , Breuer J , Baric RS . mBio 2022 13 (5) e0186122 Understanding the complex interactions between virus and host that drive new strain evolution is key to predicting the emergence potential of variants and informing vaccine development. Under our hypothesis, future dominant human norovirus GII.4 variants with critical antigenic properties that allow them to spread are currently circulating undetected, having diverged years earlier. Through large-scale sequencing of GII.4 surveillance samples, we identified two variants with extensive divergence within domains that mediate neutralizing antibody binding. Subsequent serological characterization of these strains using temporally resolved adult and child sera suggests that neither candidate could spread globally in adults with multiple GII.4 exposures, yet young children with minimal GII.4 exposure appear susceptible. Antigenic cartography of surveillance and outbreak sera indicates that continued population exposure to GII.4 Sydney 2012 and antigenically related variants over a 6-year period resulted in a broadening of immunity to heterogeneous GII.4 variants, including those identified here. We show that the strongest antibody responses in adults exposed to GII.4 Sydney 2012 are directed to previously circulating GII.4 viruses. Our data suggest that the broadening of antibody responses compromises establishment of strong GII.4 Sydney 2012 immunity, thereby allowing the continued persistence of GII.4 Sydney 2012 and modulating the cycle of norovirus GII.4 variant replacement. Our results indicate a cycle of norovirus GII.4 variant replacement dependent upon population immunity. Young children are susceptible to divergent variants; therefore, emergence of these strains worldwide is driven proximally by changes in adult serological immunity and distally by viral evolution that confers fitness in the context of immunity. IMPORTANCE In our model, preepidemic human norovirus variants harbor genetic diversification that translates into novel antigenic features without compromising viral fitness. Through surveillance, we identified two viruses fitting this profile, forming long branches on a phylogenetic tree. Neither evades current adult immunity, yet young children are likely susceptible. By comparing serological responses, we demonstrate that population immunity varies by age/exposure, impacting predicted susceptibility to variants. Repeat exposure to antigenically similar variants broadens antibody responses, providing immunological coverage of diverse variants but compromising response to the infecting variant, allowing continued circulation. These data indicate norovirus GII.4 variant replacement is driven distally by virus evolution and proximally by immunity in adults. |
First Episodes of Norovirus and Sapovirus Gastroenteritis Protect Against Subsequent Episodes in a Nicaraguan Birth Cohort.
Vielot NA , Reyes Y , Blette B , González F , Toval-Ruiz C , Gutiérrez L , Vilchez S , Diez-Valcarce M , Vinjé J , Becker-Dreps S , Bucardo F . Epidemiology 2022 33 (5) 650-653 BACKGROUND: Norovirus and sapovirus cause a large burden of acute gastroenteritis (AGE) in young children. We assessed protection conferred by norovirus and sapovirus AGE episodes against future episodes. METHODS: Between June 2017 and July 2018, we recruited 444 newborns in León, Nicaragua. Weekly household surveys identified AGE episodes over 36 months, and AGE stools were tested by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) for norovirus genogroup (G)I/GII and sapovirus. We used recurrent-event Cox models and negative control methods to estimate protection conferred by first episodes, controlling for observed and unobserved risk factors, respectively. RESULTS: Sapovirus episodes conferred a 69% reduced hazard of subsequent episodes using the negative control method. Norovirus GI (hazard ratio [HR] = 0.67; 95% confidence interval [CI] = 0.31, 1.3) and GII (HR = 0.20; 95% CI = 0.04, 0.44) episodes also appeared highly protective. Protection against norovirus GII was enhanced following two episodes. CONCLUSIONS: Evidence of natural immunity in early childhood provides optimism for the future success of pediatric norovirus and sapovirus vaccines. |
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