-
Cell Host & Microbe May 2020The live-attenuated oral poliovirus vaccine (OPV or Sabin vaccine) replicates in gut-associated tissues, eliciting mucosa and systemic immunity. OPV protects from...
The live-attenuated oral poliovirus vaccine (OPV or Sabin vaccine) replicates in gut-associated tissues, eliciting mucosa and systemic immunity. OPV protects from disease and limits poliovirus spread. Accordingly, vaccination with OPV is the primary strategy used to end the circulation of all polioviruses. However, the ability of OPV to regain replication fitness and establish new epidemics represents a significant risk of polio re-emergence should immunization cease. Here, we report the development of a poliovirus type 2 vaccine strain (nOPV2) that is genetically more stable and less likely to regain virulence than the original Sabin2 strain. We introduced modifications within at the 5' untranslated region of the Sabin2 genome to stabilize attenuation determinants, 2C coding region to prevent recombination, and 3D polymerase to limit viral adaptability. Prior work established that nOPV2 is immunogenic in preclinical and clinical studies, and thus may enable complete poliovirus eradication.
Topics: Adult; Animals; Chlorocebus aethiops; Disease Models, Animal; Female; Genetic Engineering; HeLa Cells; Humans; Immunogenicity, Vaccine; Male; Mice; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; RNA, Viral; RNA-Dependent RNA Polymerase; Recombination, Genetic; Vaccination; Vaccines, Attenuated; Vero Cells; Virulence
PubMed: 32330425
DOI: 10.1016/j.chom.2020.04.003 -
Poliomyelitis is a current challenge: long-term sequelae and circulating vaccine-derived poliovirus.GeroScience Apr 2023For more than 20 years, the World Health Organization Western Pacific Region (WPR) has been polio-free. However, two current challenges are still polio-related. First,... (Review)
Review
For more than 20 years, the World Health Organization Western Pacific Region (WPR) has been polio-free. However, two current challenges are still polio-related. First, around half of poliomyelitis elderly survivors suffer late poliomyelitis sequelae with a substantial impact on daily activities and quality of life, experiencing varying degrees of residual weakness as they age. The post-polio syndrome as well as accelerated aging may be involved. Second, after the worldwide Sabin oral poliovirus (OPV) vaccination, the recent reappearance of strains of vaccine-derived poliovirus (VDPV) circulating in the environment is worrisome and able to persistent person-to-person transmission. Such VDPV strains exhibit atypical genetic characteristics and reversed neurovirulence that can cause paralysis similarly to wild poliovirus, posing a significant obstacle to the elimination of polio. Immunization is essential for preventing paralysis in those who are exposed to the poliovirus. Stress the necessity of maintaining high vaccination rates because declining immunity increases the likelihood of reemergence. If mankind wants to eradicate polio in the near future, measures to raise immunization rates and living conditions in poorer nations are needed, along with strict observation. New oral polio vaccine candidates offer a promissory tool for this goal.
Topics: Aged; Humans; Paralysis; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Quality of Life
PubMed: 36260265
DOI: 10.1007/s11357-022-00672-7 -
Mucosal Immunology Jan 2022A cornerstone of the global initiative to eradicate polio is the widespread use of live and inactivated poliovirus vaccines in extensive public health campaigns designed... (Review)
Review
A cornerstone of the global initiative to eradicate polio is the widespread use of live and inactivated poliovirus vaccines in extensive public health campaigns designed to prevent the development of paralytic disease and interrupt transmission of the virus. Central to these efforts is the goal of inducing mucosal immunity able to limit virus replication in the intestine. Recent clinical trials have evaluated new combined regimens of poliovirus vaccines, and demonstrated clear differences in their ability to restrict virus shedding in stool after oral challenge with live virus. Analyses of mucosal immunity accompanying these trials support a critical role for enteric neutralizing IgA in limiting the magnitude and duration of virus shedding. This review summarizes key findings in vaccine-induced intestinal immunity to poliovirus in infants, older children, and adults. The impact of immunization on development and maintenance of protective immunity to poliovirus and the implications for global eradication are discussed.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Child; Humans; Immunity, Mucosal; Immunoglobulin A; Poliomyelitis; Poliovirus; Vaccination; Viral Vaccines; Virus Shedding
PubMed: 34239028
DOI: 10.1038/s41385-021-00428-0 -
Annual Review of Biochemistry Jun 2020DNA synthesis technology has progressed to the point that it is now practical to synthesize entire genomes. Quite a variety of methods have been developed, first to... (Review)
Review
DNA synthesis technology has progressed to the point that it is now practical to synthesize entire genomes. Quite a variety of methods have been developed, first to synthesize single genes but ultimately to massively edit or write from scratch entire genomes. Synthetic genomes can essentially be clones of native sequences, but this approach does not teach us much new biology. The ability to endow genomes with novel properties offers special promise for addressing questions not easily approachable with conventional gene-at-a-time methods. These include questions about evolution and about how genomes are fundamentally wired informationally, metabolically, and genetically. The techniques and technologies relating to how to design, build, and deliver big DNA at the genome scale are reviewed here. A fuller understanding of these principles may someday lead to the ability to truly design genomes from scratch.
Topics: CRISPR-Cas Systems; DNA; Escherichia coli; Gene Editing; Gene Transfer Techniques; Genes, Synthetic; Genetic Engineering; Genome; Humans; Oligonucleotides; Plasmids; Poliovirus; Saccharomyces cerevisiae; Spheroplasts
PubMed: 32569517
DOI: 10.1146/annurev-biochem-013118-110704 -
Human Vaccines & Immunotherapeutics Dec 2023Poliomyelitis is an acute infectious disease caused by poliovirus. This bibliometric analysis aims to examine the status of poliomyelitis research in the past... (Review)
Review
Poliomyelitis is an acute infectious disease caused by poliovirus. This bibliometric analysis aims to examine the status of poliomyelitis research in the past 20 years. Information regarding polio research was obtained from the Web of Science Core Collection database. CiteSpace, VOSviewer, and Excel were used to perform visual and bibliometric analysis with respect to countries/regions, institutions, authors, journals and keywords. A total of 5,335 publications on poliomyelitis were published from 2002 to 2021. The USA was the county with the majority of publications. Additionally, the most productive institution was the Centers for Disease Control and Prevention. Sutter, RW produced the most papers and had the most co-citations. was the journal with the most polio-related publications and citations. The most common keywords were mainly about polio immunology research ("polio," "immunization," "children," "eradication" and "vaccine"). Our study is helpful for identifying research hotspots and providing direction for future research on poliomyelitis.
Topics: United States; Child; Humans; Poliomyelitis; Bibliometrics; Poliovirus; Centers for Disease Control and Prevention, U.S.; Databases, Factual
PubMed: 36803526
DOI: 10.1080/21645515.2023.2173905 -
Bulletin of the World Health... Dec 2023A decrease in vaccine coverage in conflict-affected areas has placed Yemen at higher risk of polio outbreaks caused by vaccine-derived poliovirus strains.
PROBLEM
A decrease in vaccine coverage in conflict-affected areas has placed Yemen at higher risk of polio outbreaks caused by vaccine-derived poliovirus strains.
APPROACH
In response to polio outbreaks, the Yemeni health ministry and partners initiated multiple vaccination campaigns to deliver vaccines to children. We also implemented several measures to enhance communication, education, health promotion and hygiene, especially in camps for internally displaced people.
LOCAL SETTING
In 2009, Yemen achieved polio-free status and maintained it until 2019. However, the ongoing political conflict since 2015, coupled with challenges in delivering the polio vaccine to conflict-affected areas, resulted in two polio outbreaks: 35 cases caused by vaccine-derived poliovirus strain 1 between 2019 and 2021, and 230 cases due to vaccine-derived poliovirus strain 2 between November 2021 and December 2022.
RELEVANT CHANGES
In response to the first outbreak, by the end of 2020, we vaccinated 7.2 million children through nationwide vaccination campaigns, except in Sa'ada governorate due to a ban by the authorities. By the end of 2021, 3 800 313 children younger than 5 years had received polio vaccines. For the second outbreak, by the end of 2022, 4 463 389 vaccines had been given to children younger than 10 years, and 1 217 423 to those younger than 5 years.
LESSONS LEARNT
Vaccination campaigns in conflict-affected areas with low vaccine coverage remain crucial in eradicating polio. Efforts are needed to reach vulnerable groups such as displaced populations. Advocacy, communication and social mobilization actions help ensure broader public inclusion and participation in vaccination efforts to prevent polio outbreaks.
Topics: Child; Humans; Yemen; Poliomyelitis; Poliovirus; Poliovirus Vaccines; Disease Outbreaks
PubMed: 38024246
DOI: 10.2471/BLT.23.290122 -
Virologie (Montrouge, France) Jul 2022
Topics: Phantoms, Imaging; Poliovirus
PubMed: 36120973
DOI: 10.1684/vir.2022.0964 -
Nature Aug 2021Viral pathogens are an ongoing threat to public health worldwide. Analysing their dependence on host biosynthetic pathways could lead to effective antiviral therapies....
Viral pathogens are an ongoing threat to public health worldwide. Analysing their dependence on host biosynthetic pathways could lead to effective antiviral therapies. Here we integrate proteomic analyses of polysomes with functional genomics and pharmacological interventions to define how enteroviruses and flaviviruses remodel host polysomes to synthesize viral proteins and disable host protein production. We find that infection with polio, dengue or Zika virus markedly modifies polysome composition, without major changes to core ribosome stoichiometry. These viruses use different strategies to evict a common set of translation initiation and RNA surveillance factors from polysomes while recruiting host machineries that are specifically required for viral biogenesis. Targeting these specialized viral polysomes could provide a new approach for antiviral interventions. For example, we find that both Zika and dengue use the collagen proline hydroxylation machinery to mediate cotranslational modification of conserved proline residues in the viral polyprotein. Genetic or pharmacological inhibition of proline hydroxylation impairs nascent viral polyprotein folding and induces its aggregation and degradation. Notably, such interventions prevent viral polysome remodelling and lower virus production. Our findings delineate the modular nature of polysome specialization at the virus-host interface and establish a powerful strategy to identify targets for selective antiviral interventions.
Topics: Cell Line; Collagen; Dengue Virus; Flavivirus; Gene Expression Regulation, Viral; Genomics; Host-Derived Cellular Factors; Host-Pathogen Interactions; Humans; Hydroxylation; Internal Ribosome Entry Sites; Molecular Chaperones; Peptide Chain Initiation, Translational; Poliovirus; Polyribosomes; Procollagen-Proline Dioxygenase; Proline; Protein Aggregates; Protein Biosynthesis; Protein Folding; Protein Interaction Maps; Proteolysis; Proteomics; Zika Virus
PubMed: 34408324
DOI: 10.1038/s41586-021-03851-2 -
Nucleic Acids Research Sep 2023The genomes of positive-strand RNA viruses serve as a template for both protein translation and genome replication. In enteroviruses, a cloverleaf RNA structure at the...
The genomes of positive-strand RNA viruses serve as a template for both protein translation and genome replication. In enteroviruses, a cloverleaf RNA structure at the 5' end of the genome functions as a switch to transition from viral translation to replication by interacting with host poly(C)-binding protein 2 (PCBP2) and the viral 3CDpro protein. We determined the structures of cloverleaf RNA from coxsackievirus and poliovirus. Cloverleaf RNA folds into an H-type four-way junction and is stabilized by a unique adenosine-cytidine-uridine (A•C-U) base triple involving the conserved pyrimidine mismatch region. The two PCBP2 binding sites are spatially proximal and are located on the opposite end from the 3CDpro binding site on cloverleaf. We determined that the A•C-U base triple restricts the flexibility of the cloverleaf stem-loops resulting in partial occlusion of the PCBP2 binding site, and elimination of the A•C-U base triple increases the binding affinity of PCBP2 to the cloverleaf RNA. Based on the cloverleaf structures and biophysical assays, we propose a new mechanistic model by which enteroviruses use the cloverleaf structure as a molecular switch to transition from viral protein translation to genome replication.
Topics: Humans; Enterovirus; Genome, Viral; HeLa Cells; Nucleic Acid Conformation; Poliovirus; Protein Biosynthesis; RNA, Viral; RNA-Binding Proteins; Viral Proteins; Virus Replication
PubMed: 37486760
DOI: 10.1093/nar/gkad618 -
Vaccine Jan 2022To describe in chronological detail Pakistan's decades long battle against poliovirus and evaluate the multiple factors impacting it.
BACKGROUND
To describe in chronological detail Pakistan's decades long battle against poliovirus and evaluate the multiple factors impacting it.
MAIN BODY
Pakistan's fight is documented through various published research articles and reports on Pakistan's progress in eradication of polio published by international agencies involved in elimination of poliovirus worldwide. The socioeconomic, religious, and political factors, violent religious militancy, conspiracy theories resulting in vaccine refusals are documented in detail emphasizing the ups and downs in the fight at different times since 1994 to present. Pakistan and Afghanistan are the only two countries in the world reporting cases caused by wild polio virus type 1 (WPV1) since 2017 and the only two countries that have never stopped the transmission of WPV1 Pakistan needs to work on a war footing to eliminate the disease. The need to act urgently is now being increasingly recognized by the Pakistani Government.
CONCLUSION
Many difficulties still remain. Pakistan has reached a critical stage in the fight against polio. The world will not accept any further delay or complacency as there is apprehension around the world that Pakistan may "export" polio to other countries and undermine the worldwide success in eradicating polio.
Topics: Disease Eradication; Humans; Immunization Programs; Pakistan; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Population Surveillance; Vaccination
PubMed: 34955324
DOI: 10.1016/j.vaccine.2021.11.095