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The Lancet. Microbe Dec 2022Sabin strains used in oral poliovirus vaccines (OPV) can revert to virulence and, in rare instances, cause disease or generate vaccine-derived strains leading to...
Genetic and phenotypic stability of poliovirus shed from infants who received novel type 2 or Sabin type 2 oral poliovirus vaccines in Panama: an analysis of two clinical trials.
BACKGROUND
Sabin strains used in oral poliovirus vaccines (OPV) can revert to virulence and, in rare instances, cause disease or generate vaccine-derived strains leading to outbreaks in areas of low immunisation coverage. A novel OPV2 (nOPV2) was designed to stabilise the viral genome against reversion and reduce recombination events that might lead to virulent strains. In this study, we evaluated the genetic and phenotypic stability of shed poliovirus following administration of one dose of monovalent OPV2 (mOPV2) or nOPV2 to infants aged 18-22 weeks.
METHODS
In two similarly designed clinical trials (NCT02521974 and NCT03554798) conducted in Panama, infants aged 18-22-weeks, after immunisation with three doses of bivalent OPV (types 1 and 3) and one dose of inactivated poliovirus vaccine, were administered one or two doses of mOPV2 or nOPV2. In this analysis of two clinical trials, faecally shed polioviruses following one dose of mOPV2 or nOPV2 were isolated from stools meeting predetermined criteria related to sample timing and viral presence and quantity and assessed for nucleotide polymorphisms using next-generation sequencing. A transgenic mouse neurovirulence test was adapted to assess the effect of the possible phenotypic reversion of shed mOPV2 and nOPV2 with a logistic regression model.
FINDINGS
Of the 91 eligible samples, 86 were able to be sequenced, with 72 evaluated in the transgenic mouse assay. Sabin-2 poliovirus reverts rapidly at nucleotide 481, the primary attenuation site in domain V of the 5' untranslated region of the genome. There was no evidence of neurovirulence-increasing polymorphisms in domain V of shed nOPV2. Reversion of shed Sabin-2 virus corresponded with unadjusted paralysis rates of 47·6% at the 4 log 50% cell culture infectious dose (CCID) and 76·7% at the 5 log CCID inoculum levels, with rates of 2·8% for 4 log CCID and 11·8% for 5 log CCID observed for shed nOPV2 samples. The estimated adjusted odds ratio at 4·5 log of 0·007 (95% CI 0·002-0·023; p<0·0001) indicates significantly reduced odds of mouse paralysis from virus obtained from nOPV2 recipients compared with mOPV2 recipients.
INTERPRETATION
The data indicate increased genetic stability of domain V of nOPV2 relative to mOPV2, with significantly lower neurovirulence of shed nOPV2 virus compared with shed mOPV2. While this vaccine is currently being deployed under an emergency use listing, the data on the genetic stability of nOPV2 will support further regulatory and policy decision-making regarding use of nOPV2 in outbreak responses.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Mice; Animals; Poliovirus; Poliomyelitis; Poliovirus Vaccine, Oral; 5' Untranslated Regions; Mice, Transgenic; Paralysis; Nucleotides
PubMed: 36332645
DOI: 10.1016/S2666-5247(22)00254-3 -
MSphere Apr 2019Several viruses encounter various bacterial species within the host and in the environment. Despite these close encounters, the effects of bacteria on picornaviruses are...
Several viruses encounter various bacterial species within the host and in the environment. Despite these close encounters, the effects of bacteria on picornaviruses are not completely understood. Previous work determined that poliovirus (PV), an enteric virus, has enhanced virion stability when exposed to bacteria or bacterial surface polysaccharides such as lipopolysaccharide. Virion stabilization by bacteria may be important for interhost transmission, since a mutant PV with reduced bacterial binding had a fecal-oral transmission defect in mice. Therefore, we investigated whether bacteria broadly enhance stability of picornaviruses from three different genera: (PV and coxsackievirus B3 [CVB3]), (Aichi virus), and (mengovirus). Furthermore, to delineate strain-specific effects, we examined two strains of CVB3 and a PV mutant with enhanced thermal stability. We determined that specific bacterial strains enhance thermal stability of PV and CVB3, while mengovirus and Aichi virus are stable at high temperatures in the absence of bacteria. Additionally, we determined that bacteria or lipopolysaccharide can stabilize PV, CVB3, Aichi virus, and mengovirus during exposure to bleach. These effects are likely mediated through direct interactions with bacteria, since viruses bound to bacteria in a pulldown assay. Overall, this work reveals shared and distinct effects of bacteria on a panel of picornaviruses. Recent studies have shown that bacteria promote infection and stabilization of poliovirus particles, but the breadth of these effects on other members of the family is unknown. Here, we compared the effects of bacteria on four distinct members of the family. We found that bacteria reduced inactivation of all of the viruses during bleach treatment, but not all viral strains were stabilized by bacteria during heat treatment. Overall, our data provide insight into how bacteria play differential roles in picornavirus stability.
Topics: Bacteria; Cardiovirus; Enterovirus; Hot Temperature; Kobuvirus; Microbial Interactions; Mutation; Picornaviridae; Poliovirus; Sodium Hypochlorite; Virus Inactivation
PubMed: 30944213
DOI: 10.1128/mSphere.00183-19 -
Viruses Jul 2021The oral poliovirus vaccine (OPV), which prevents person-to-person transmission of poliovirus by inducing robust intestinal immunity, has been a crucial tool for global... (Review)
Review
The oral poliovirus vaccine (OPV), which prevents person-to-person transmission of poliovirus by inducing robust intestinal immunity, has been a crucial tool for global polio eradication. However, polio outbreaks, mainly caused by type 2 circulating vaccine-derived poliovirus (cVDPV2), are increasing worldwide. Meanwhile, immunodeficiency-associated vaccine-derived poliovirus (iVDPV) is considered another risk factor during the final stage of global polio eradication. Patients with primary immunodeficiency diseases are associated with higher risks for long-term iVDPV infections. Although a limited number of chronic iVDPV excretors were reported, the recent identification of a chronic type 2 iVDPV (iVDPV2) excretor in the Philippines highlights the potential risk of inapparent iVDPV infection for expanding cVDPV outbreaks. Further research on the genetic characterizations and molecular evolution of iVDPV2, based on comprehensive iVDPV surveillance, will be critical for elucidating the remaining risk of iVDPV2 during the post-OPV era.
Topics: Disease Eradication; Disease Outbreaks; Evolution, Molecular; Global Health; Humans; Immunocompromised Host; Poliovirus; Poliovirus Vaccine, Oral; Primary Immunodeficiency Diseases; Vaccination
PubMed: 34372613
DOI: 10.3390/v13071407 -
Journal of Virology Dec 2019Accumulating evidence suggests that intestinal bacteria promote enteric virus infection in mice. For example, previous work demonstrated that antibiotic treatment of...
Accumulating evidence suggests that intestinal bacteria promote enteric virus infection in mice. For example, previous work demonstrated that antibiotic treatment of mice prior to oral infection with poliovirus reduced viral replication and pathogenesis. Here, we examined the effect of antibiotic treatment on infection with coxsackievirus B3 (CVB3), a picornavirus closely related to poliovirus. We treated mice with a mixture of five antibiotics to deplete host microbiota and examined CVB3 replication and pathogenesis following oral inoculation. We found that, as seen with poliovirus, CVB3 shedding and pathogenesis were reduced in antibiotic-treated mice. While treatment with just two antibiotics, vancomycin and ampicillin, was sufficient to reduce CVB3 replication and pathogenesis, this treatment had no effect on poliovirus. The quantity and composition of bacterial communities were altered by treatment with the five-antibiotic cocktail and by treatment with vancomycin and ampicillin. To determine whether more-subtle changes in bacterial populations impact viral replication, we examined viral infection in mice treated with milder antibiotic regimens. Mice treated with one-tenth the standard concentration of the normal antibiotic cocktail supported replication of poliovirus but not CVB3. Importantly, a single dose of one antibiotic, streptomycin, was sufficient to reduce CVB3 shedding and pathogenesis while having no effect on poliovirus shedding and pathogenesis. Overall, replication and pathogenesis of CVB3 are more sensitive to antibiotic treatment than poliovirus, indicating that closely related viruses may differ with respect to their reliance on microbiota. Recent data indicate that intestinal bacteria promote intestinal infection of several enteric viruses. Here, we show that coxsackievirus, an enteric virus in the picornavirus family, also relies on microbiota for intestinal replication and pathogenesis. Relatively minor depletion of the microbiota was sufficient to decrease coxsackievirus infection, while poliovirus infection was unaffected. Surprisingly, a single dose of one antibiotic was sufficient to reduce coxsackievirus infection. Therefore, these data indicate that closely related viruses may differ with respect to their reliance on microbiota.
Topics: Ampicillin; Animals; Anti-Bacterial Agents; Bacteria; Coxsackievirus Infections; Disease Models, Animal; Enterovirus; Enterovirus Infections; HeLa Cells; Humans; Male; Mice; Mice, Inbred C57BL; Microbiota; Picornaviridae; Poliovirus; Vancomycin; Virus Replication
PubMed: 31511379
DOI: 10.1128/JVI.01339-19 -
Bulletin of the World Health... May 2023Individuals with primary immunodeficiencies who are infected with vaccine-derived polioviruses may continue to shed poliovirus for months and go undetected by...
Individuals with primary immunodeficiencies who are infected with vaccine-derived polioviruses may continue to shed poliovirus for months and go undetected by surveillance programmes of acute flaccid paralysis. These patients therefore pose a risk of initiating poliovirus outbreaks that jeopardize efforts towards global polio eradication. To identify these individuals, we designed a study protocol for the establishment of a network for surveillance of immunodeficiency-related vaccine-derived poliovirus in India. In the first step we identified recognized centres in India that could diagnose and enrol patients with primary immunodeficiency disorder into the study. Stool sample collection from study sites, culture, isolation, characterization of enteroviruses and reporting to study sites was carried out at the National Institute of Virology Mumbai Unit, as per the WHO national polio surveillance project protocol. In the first phase of the study from January 2020 to December 2021, we implemented the protocol at seven study sites at different medical institutes to determine the proportion of poliovirus infections in primary immunodeficiency disorder patients of India. We later expanded the study by including an additional 14 medical institutes across the country in the second phase running from January 2022 to December 2023. We believe this study protocol will help other countries to initiate immunodeficiency-related vaccine-derived poliovirus surveillance to identify and follow up patients who are long-term excretors of vaccine-derived poliovirus. Integration of immunodeficiency-related poliovirus surveillance with acute flaccid paralysis surveillance of the existing poliovirus network will enhance continuous screening of patients with primary immunodeficiency disorder in the future.
Topics: Humans; Poliovirus; Poliomyelitis; India; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Population Surveillance
PubMed: 37131936
DOI: 10.2471/BLT.22.289066 -
Viruses Oct 2017: Autophagy-related (Atg) gene-encoded proteins were originally described for their crucial role in macroautophagy, a catabolic pathway for cytoplasmic constituent... (Review)
Review
: Autophagy-related (Atg) gene-encoded proteins were originally described for their crucial role in macroautophagy, a catabolic pathway for cytoplasmic constituent degradation in lysosomes. Recently it has become clear that modules of this machinery can also be used to influence endo- and exocytosis. This mini review discusses how these alternative Atg functions support virus replication and viral antigen presentation on major histocompatibility (MHC) class I and II molecules. A better understanding of the modular use of the macroautophagy machinery might enable us to manipulate these alternative functions of Atg proteins during anti-viral therapies and to attenuate virus-induced immune pathologies.
Topics: Antigen Presentation; Autophagy; Enterovirus B, Human; Exocytosis; Herpesvirus 3, Human; Herpesvirus 4, Human; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Humans; Poliovirus; Viral Proteins; Virus Activation; Virus Replication; Viruses
PubMed: 28976939
DOI: 10.3390/v9100288 -
Emerging Infectious Diseases Oct 2022Environmental surveillance for poliovirus is increasingly used in poliovirus eradication efforts as a supplement to acute flaccid paralysis (AFP) surveillance....
Environmental surveillance for poliovirus is increasingly used in poliovirus eradication efforts as a supplement to acute flaccid paralysis (AFP) surveillance. Environmental surveillance was officially established in 2017 in Senegal, where no poliovirus had been detected since 2010. We tested sewage samples from 2 sites in Dakar monthly for polioviruses. We identified a vaccine-derived poliovirus serotype 2 on January 19, 2021, from a sample collected on December 24, 2020; by December 31, 2021, we had detected 70 vaccine-derived poliovirus serotype 2 isolates circulating in 7 of 14 regions in Senegal. Sources included 18 AFP cases, 20 direct contacts, 17 contacts in the community, and 15 sewage samples. Phylogenetic analysis revealed the circulation of 2 clusters and provided evidence on the virus introduction from Guinea. Because novel oral polio vaccine serotype 2 was used for response activities throughout Senegal, we recommend expanding environmental surveillance into other regions.
Topics: Humans; Environmental Monitoring; Phylogeny; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Senegal; Serogroup; Sewage
PubMed: 36148906
DOI: 10.3201/eid2810.220847 -
Polish Journal of Microbiology Mar 2018As a complement to the active search for cases of acute flaccid paralysis, environmental sampling was conducted from January to December 2011, to test for any putative...
As a complement to the active search for cases of acute flaccid paralysis, environmental sampling was conducted from January to December 2011, to test for any putative polio revertants and recombinants in sewage. A total of 165 environmental samples were obtained and analyzed for the presence of polioviruses by use of cell culture (L20B, RD and Caco-2) followed by neutralization and reverse-transcription polymerase chain reaction. Out of the 31 CPE positive samples, 26 contained one and 5 two different serotypes, yielding a total of 36 PVs. The microneutralization test revealed the presence of 7, 10 and 19 strains belonging to poliovirus serotype 1, 2 and 3, respectively. The genomic variability of 36 poliovirus strains was examined by the restriction fragment length polymorphism assay (RFLP). By combined analyses of two distant, polymorphic segments of the viral genome, one situated in the capsid protein VP1 coding region and the other in the 3D-polymerase coding region, we screened for the putative poliovirus revertants and recombinants. All detected PVs were classified as vaccine strains on the basis of RFLP-VP1 test. None of wild-type PVs or vaccine derived polioviruses were detected. RFLP assay also revealed the presence of 11 recombinants in 3D-polymerase coding region. Nine isolates appeared to be S3/S2, one S3/S1 and S1/S2 recombinant in analyzed 3Dpol region. This study revealed, through environmental monitoring, the introduction of SL PVs into the population associated with the routine use of OPV in Poland before the April 2016. Our findings demonstrate the usefulness of environmental surveillance in the overall polio eradication program.
Topics: Capsid Proteins; Environmental Monitoring; Genome, Viral; Humans; Neutralization Tests; Poland; Poliovirus; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Sequence Analysis, DNA; Serogroup; Sewage
PubMed: 30015429
DOI: 10.5604/01.3001.0011.6147 -
Viruses Sep 2022Following the success of global vaccination programmes using the live-attenuated oral and inactivated poliovirus vaccines (OPV and IPV), wild poliovirus (PV) is now only...
Following the success of global vaccination programmes using the live-attenuated oral and inactivated poliovirus vaccines (OPV and IPV), wild poliovirus (PV) is now only endemic in Afghanistan and Pakistan. However, the continued use of these vaccines poses potential risks to the eradication of PV. The production of recombinant PV virus-like particles (VLPs), which lack the viral genome offer great potential as next-generation vaccines for the post-polio world. We have previously reported production of PV VLPs using , however, these VLPs were in the non-native conformation (C Ag), which would not produce effective protection against PV. Here, we build on this work and show that it is possible to produce wt PV-3 and thermally stabilised PV-3 (referred to as PV-3 SC8) VLPs in the native conformation (D Ag) using . We show that the PV-3 SC8 VLPs provide a much-improved D:C antigen ratio as compared to wt PV-3, whilst exhibiting greater thermostability than the current IPV vaccine. Finally, we determine the cryo-EM structure of the yeast-derived PV-3 SC8 VLPs and compare this to previously published PV-3 D Ag structures, highlighting the similarities between these recombinantly expressed VLPs and the infectious virus, further emphasising their potential as a next-generation vaccine candidate for PV.
Topics: Humans; Antibodies, Viral; Poliovirus; Poliovirus Vaccines; Poliomyelitis; Poliovirus Vaccine, Oral
PubMed: 36298714
DOI: 10.3390/v14102159 -
Applied Biochemistry and Biotechnology Mar 2017In conjunction with an increasing public awareness of infectious diseases, the textile industry and scientists are developing hygienic fabrics by the addition of various...
In conjunction with an increasing public awareness of infectious diseases, the textile industry and scientists are developing hygienic fabrics by the addition of various antimicrobial and antiviral compounds. In the current study, sodium pentaborate pentahydrate and triclosan are applied to cotton fabrics in order to gain antimicrobial and antiviral properties for the first time. The antimicrobial activity of textiles treated with 3 % sodium pentaborate pentahydrate, 0.03 % triclosan, and 7 % Glucapon has been investigated against a broad range of microorganisms including bacteria, yeast, and fungi. Moreover, modified cotton fabrics were tested against adenovirus type 5 and poliovirus type 1. According to the test results, the modified textile goods attained very good antimicrobial and antiviral properties. Thus, the results of the present study clearly suggest that sodium pentaborate pentahydrate and triclosan solution-treated textiles can be considered in the development of antimicrobial and antiviral textile finishes.
Topics: Adenoviridae; Anti-Bacterial Agents; Antiviral Agents; Bacteria; Cell Line; Cotton Fiber; Humans; Poliovirus
PubMed: 27734286
DOI: 10.1007/s12010-016-2275-5