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Vaccines Sep 2023The oral poliovirus vaccine (OPV) has been the mainstay of polio eradication, especially in low-income countries, and its use has eliminated wild poliovirus type 2....
The oral poliovirus vaccine (OPV) has been the mainstay of polio eradication, especially in low-income countries, and its use has eliminated wild poliovirus type 2. However, the inactivated poliovirus vaccine (IPV) is safer than OPV, as IPV protects against paralytic poliomyelitis without producing adverse reactions. The present study compared mucosal and humoral responses to poliovirus vaccines administered to previously OPV-immunized children to assess the immunity gap in children in areas of high poliovirus transmission. A cluster-randomized trial was implemented in three high-risk districts of Pakistan-Karachi, Kashmore, and Bajaur-from June 2013 to May 2014. This trial was community-oriented and included three arms, focusing on healthy children below five years of age. The study involved the randomization of 387 clusters, of which 360 were included in the final analysis. The control arm (A) received the routine polio program bivalent poliovirus vaccine (bOPV). The second arm (B) received additional interventions, including health camps providing routine vaccinations and preventive maternal and child health services. In addition to the interventions in arm B, the third arm (C) was also provided with IPV. Blood and stool samples were gathered from children to evaluate humoral and intestinal immunity. The highest levels of poliovirus type 1 serum antibodies were observed in Group C (IPV + OPV). The titers for poliovirus type 2 (P2) and poliovirus type 3 (P3) were noticeably higher in those who had received a routine OPV dose than in those who had not across all study groups and visits. Providing an IPV booster after at least two OPV doses could potentially fill immunity gaps in regions where OPV does not show high efficacy. However, IPV only marginally enhances humoral immunity and fails to offer intestinal immunity, which is critical to stop the infection and spread of live poliovirus in populations that have not been exposed before.
PubMed: 37766121
DOI: 10.3390/vaccines11091444 -
The Journal of Infection May 2024In this study, we investigated the causes of measles-like illnesses (MLI) in the Uganda national surveillance program in order to inform diagnostic assay selection and...
OBJECTIVES
In this study, we investigated the causes of measles-like illnesses (MLI) in the Uganda national surveillance program in order to inform diagnostic assay selection and vaccination strategies.
METHODS
We used metagenomic next-generation sequencing (M-NGS) on the Illumina platform to identify viruses associated with MLI (defined as fever and rash in the presence of either cough, coryza or conjunctivitis) in patient samples that had tested IgM negative for measles between 2010 and 2019.
RESULTS
Viral genomes were identified in 87/271 (32%) of samples, of which 44/271 (16%) contained 12 known viral pathogens. Expected viruses included rubella, human parvovirus B19, Epstein Barr virus, human herpesvirus 6B, human cytomegalovirus, varicella zoster virus and measles virus (detected within the seronegative window-period of infection) and the blood-borne hepatitis B virus. We also detected Saffold virus, human parvovirus type 4, the human adenovirus C2 and vaccine-associated poliovirus type 1.
CONCLUSIONS
The study highlights the presence of undiagnosed viruses causing MLI in Uganda, including vaccine-preventable illnesses. NGS can be used to monitor common viral infections at a population level, especially in regions where such infections are prevalent, including low and middle income countries to guide vaccination policy and optimize diagnostic assays.
Topics: Humans; Uganda; Child, Preschool; Measles; Infant; Child; High-Throughput Nucleotide Sequencing; Male; Female; Adolescent; Viruses; Genome, Viral; Adult; Young Adult; Virus Diseases; Metagenomics; Measles virus
PubMed: 38588959
DOI: 10.1016/j.jinf.2024.106148 -
NPJ Vaccines Sep 2023There is an increasing burden of circulating vaccine-derived polioviruses (cVDPVs) due to the continued use of oral poliovirus vaccine (OPV). However, the...
There is an increasing burden of circulating vaccine-derived polioviruses (cVDPVs) due to the continued use of oral poliovirus vaccine (OPV). However, the informativeness of routine OPV VP1 sequencing for the early identification of viruses carrying virulence-associated reversion mutations has not been directly evaluated in a controlled setting. We prospectively collected 15,331 stool samples to track OPV shedding from children receiving OPV and their contacts for ten weeks following an immunization campaign in Veracruz State, Mexico and sequenced VP1 genes from 358 samples. We found that OPV was genetically unstable and evolves at an approximately clocklike rate that varies across serotypes and by vaccination status. Overall, 61% (11/18) of OPV-1, 71% (34/48) OPV-2, and 96% (54/56) OPV-3 samples with available data had evidence of a reversion at the key 5' UTR attenuating position and 28% (13/47) of OPV-1, 12% (14/117) OPV-2, and 91% (157/173) OPV-3 of Sabin-like viruses had ≥1 known reversion mutations in the VP1 gene. Our results are consistent with previous work documenting rapid reversion to virulence of OPV and underscores the need for intensive surveillance following OPV use.
PubMed: 37749086
DOI: 10.1038/s41541-023-00740-9 -
Le Infezioni in Medicina 2024After a long global battle with wild poliovirus, the virus has been defeated through researches and vaccination using the oral polio vaccine and inactivated polio...
After a long global battle with wild poliovirus, the virus has been defeated through researches and vaccination using the oral polio vaccine and inactivated polio vaccine as well as sensitization. The issue that is now of global concern is that of vaccine-derived poliovirus which emerged from the unstable oral polio vaccine. Ninety sewage water samples were collected from slums in Maiduguri using grab method, concentrated using two phase separation method and subjected to intratypic differentiation and vaccine-derived poliovirus screening. The result revealed the presence of Sabin 1in 17 samples (61.0%) and Sabin 3 in 22 samples (79.0%), all of which were positive after vaccine-derived poliovirus screening. The presence of strains of Sabin 1 and Sabin 3 in the sewage water samples collected is an indication of virus shedding in individuals which could be as a result of vaccination or contact with the faeces infected or vaccinated individuals.
PubMed: 38456020
DOI: 10.53854/liim-3201-12 -
Viruses Jun 2024Recently, a multiplex PCR-based titration (MPBT) assay was developed for simultaneous determination of infectious titers of all three Sabin strains of the oral...
Recently, a multiplex PCR-based titration (MPBT) assay was developed for simultaneous determination of infectious titers of all three Sabin strains of the oral poliovirus vaccine (OPV) to replace the conventional CCID assay, which is both time-consuming and laborious. The MPBT assay was shown to be reproducible, robust and sensitive. The conventional and MPBT assays showed similar results and sensitivity. The MPBT assay can be completed in two to three days, instead of ten days for the conventional assay. To prevent attenuated vaccine strains of poliovirus from reversion to virulence, a novel, genetically stable OPV (nOPV) was developed by modifying the genomes of conventional Sabin strains used in OPV. In this work, we evaluated the MPBT assay as a rapid screening tool to support trivalent nOPV (tnOPV) formulation development by simultaneous titration of the three nOPV strains to confirm stability as needed, for the selection of the lead tnOPV formulation candidate. We first assessed the ability of the MPBT assay to discriminate a 0.5 log titer difference by titrating the two tnOPV samples (undiluted and threefold-diluted) on the same plate. Once the assay was shown to be discriminating, we then tested different formulations of tnOPV drug products (DPs) that were subjected to different exposure times at 37 °C (untreated group and treated groups: 2 and 7 days at 37 °C), and to three freeze and thaw (FT) cycles. Final confirmation of the down selected formulation candidates was achieved by performing the conventional CCID assay, comparing the stability of untreated and treated groups and FT stability testing on the top three candidates. The results showed that the MPBT assay generates similar titers as the conventional assay. By testing two trivalent samples in the same plate, the assay can differentiate a 0.5 log difference between the titers of the tested nOPV samples. Also, the assay was able to detect the gradual degradation of nOPV viruses with different formulation compositions and under different time/temperature conditions and freeze/thaw cycles. We found that there were three tnOPV formulations which met the stability criteria of less than 0.5 log loss after 2 days' exposure to 37 ℃ and after three FT cycles, maintaining the potency of all three serotypes in these formulations. The ability of the MPBT assay to titrate two tnOPV lots (six viruses) in the same plate makes it cheaper and gives it a higher throughput for rapid screening. The assay detected the gradual degradation of the tnOPV and was successful in the selection of optimal formulations for the tnOPV. The results demonstrated that the MPBT method can be used as a stability indicating assay to assess the thermal stability of the nOPV. It can be used for rapid virus titer determination during the vaccine manufacturing process, and in clinical trials. The MPBT assay can be automated and applied for other viruses, including those with no cytopathic effect.
Topics: Poliovirus Vaccine, Oral; Poliovirus; Humans; Multiplex Polymerase Chain Reaction; Poliomyelitis; Vaccines, Attenuated; Reproducibility of Results; Sensitivity and Specificity
PubMed: 38932253
DOI: 10.3390/v16060961 -
The Pan African Medical Journal 2023in August 2020, the World Health Organization African Region was certified free of wild poliovirus (WPV) when Nigeria became the last African country to interrupt wild...
INTRODUCTION
in August 2020, the World Health Organization African Region was certified free of wild poliovirus (WPV) when Nigeria became the last African country to interrupt wild poliovirus transmission. The National Polio Emergency Operations Center instituted in 2012 to coordinate and manage Nigerian polio eradication efforts reviewed the epidemiology of WPV cases during 2000-2020 to document lessons learned.
METHODS
we analyzed reported WPV cases by serotype based on age, oral poliovirus vaccine immunization history, month and year of reported cases, and annual geographic distribution based on incidence rates at the Local Government Area level. The observed trends of cases were related to major events and the poliovirus vaccines used during mass vaccination campaigns within the analysis period.
RESULTS
a total of 3,579 WPV type 1 and 1,548 WPV type 3 laboratory-confirmed cases were reported with onset during 2000-2020. The highest WPV incidence rates per 100,000 population in Local Government Areas were 19.4, 12.0, and 11.3, all in 2006. Wild poliovirus cases were reported each year during 2000-2014; the endemic transmission went undetected throughout 2015 until the last cases in 2016. Ten events/milestones were highlighted, including insurgency in the northeast which led to a setback in 2016 with four cases from children previously trapped in security-compromised areas.
CONCLUSION
Nigeria interrupted WPV transmission despite the challenges faced because of the emergency management approach, implementation of mass vaccination campaigns, the commitment of the government agencies, support from global polio partners, and special strategies deployed to conduct vaccination and surveillance in the security-compromised areas.
Topics: Child; Humans; Poliovirus; Nigeria; Population Surveillance; Poliomyelitis; Poliovirus Vaccines; Poliovirus Vaccine, Oral; Immunization Programs; Disease Eradication
PubMed: 38370099
DOI: 10.11604/pamj.supp.2023.45.2.38079 -
Pathogens (Basel, Switzerland) Mar 2024A sharp rise in circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks in the years following the cessation of routine use of poliovirus type 2-containing oral... (Review)
Review
A sharp rise in circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks in the years following the cessation of routine use of poliovirus type 2-containing oral polio vaccine and the trend of seeding new emergences with suboptimal vaccination response during the same time-period led to the accelerated development of the novel oral polio vaccine type 2 (nOPV2), a vaccine with enhanced genetic stability and lower likelihood of reversion to neuroparalytic variants compared to its Sabin counterpart. In November 2020, nOPV2 became the first vaccine to be granted an Emergency Use Listing (EUL) by the World Health Organization (WHO) Prequalification Team (PQT), allowing close to a billion doses to be used by countries within three years after its first rollout and leading to full licensure and WHO prequalification (PQ) in December 2023. The nOPV2 development process exemplifies how scientific advances and innovative tools can be applied to combat global health emergencies in an urgent and adaptive way, building on a collaborative effort among scientific, regulatory and implementation partners and policymakers across the globe.
PubMed: 38668228
DOI: 10.3390/pathogens13040273 -
BMJ Open Jul 2023This study investigated the association between vaccine stockout and immunisation coverage, and infant/under 5 mortality rates.
OBJECTIVES
This study investigated the association between vaccine stockout and immunisation coverage, and infant/under 5 mortality rates.
DESIGN
A retrospective cohort study.
SETTING
Low-income and middle-income countries.
PARTICIPANTS
A cohort of 131 low-income and middle-income countries from 2004 to 2019.
PRIMARY OUTCOME MEASURES
Main outcomes included immunisation coverages of (1) diphtheria-tetanus-pertussis containing vaccine (DTP), (2) measles containing vaccine (MCV), (3) BCG and (4) oral polio vaccine (OPV). We also included infant and under 5 mortality rates as secondary outcomes.
RESULTS
The countries that experienced national-level stockouts of DTP and MCV had 3.7 and 4 percentage points lower coverage rates of DTP3 and MCV1, respectively, compared with the countries without the stockout events (p<0.01). Moreover, the statistically significant differences in the immunisation coverage rates across the countries with and without the stockout events are 2.4 percentage points and 2.6 percentage points for BCG and OPV, respectively (p<0.01).
CONCLUSION
Our findings show that the incidence of vaccine stockout events is associated with the decreased immunisation coverages for children in low-income and middle-income countries. However, we did not observe a statistically significant association between the increasing frequency of vaccine stockout and infant and under 5 mortality rates.
Topics: Infant; Child; Humans; Vaccination Coverage; BCG Vaccine; Developing Countries; Retrospective Studies; Poverty; Diphtheria-Tetanus-Pertussis Vaccine; Measles Vaccine; Poliovirus Vaccine, Oral; Vaccination
PubMed: 37524556
DOI: 10.1136/bmjopen-2023-072364 -
BioRxiv : the Preprint Server For... Feb 2024Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in...
BACKGROUND & AIMS
Human intestinal enteroids (HIEs) are gaining recognition as physiologically relevant models of the intestinal epithelium. While HIEs from adults are used extensively in biomedical research, few studies have used HIEs from infants. Considering the dramatic developmental changes that occur during infancy, it is important to establish models that represent infant intestinal characteristics and physiological responses.
METHODS
We established jejunal HIEs from infant surgical samples and performed comparisons to jejunal HIEs from adults using RNA sequencing (RNA-Seq) and morphologic analyses. We validated differences in key pathways through functional studies and determined if these cultures recapitulate known features of the infant intestinal epithelium.
RESULTS
RNA-Seq analysis showed significant differences in the transcriptome of infant and adult HIEs, including differences in genes and pathways associated with cell differentiation and proliferation, tissue development, lipid metabolism, innate immunity, and biological adhesion. Validating these results, we observed a higher abundance of cells expressing specific enterocyte, goblet cell and enteroendocrine cell markers in differentiated infant HIE monolayers, and greater numbers of proliferative cells in undifferentiated 3D cultures. Compared to adult HIEs, infant HIEs portray characteristics of an immature gastrointestinal epithelium including significantly shorter cell height, lower epithelial barrier integrity, and lower innate immune responses to infection with an oral poliovirus vaccine.
CONCLUSIONS
HIEs established from infant intestinal tissues reflect characteristics of the infant gut and are distinct from adult cultures. Our data support the use of infant HIEs as an ex-vivo model to advance studies of infant-specific diseases and drug discovery for this population.
PubMed: 37292968
DOI: 10.1101/2023.05.19.541350 -
Virology Journal Aug 2023Acute flaccid paralysis (AFP) is a rare side effect of the oral polio vaccine but can be associated with outbreaks and permanent disability in patients harboring...
Acute flaccid paralysis (AFP) is a rare side effect of the oral polio vaccine but can be associated with outbreaks and permanent disability in patients harboring circulating vaccine-derived polioviruses (cVDPVs). With the advancement of polio abolition in a glimpse, cVDPVs are causing outbreaks and slowing the polio eradication process. The polio virus protein 1 (VP1) contains the binding site that is key for virus transmission. Understanding the evolution of VP1 among AFP patients could yield more insight into the early events of cVDPVs. Polioviruses were identified from stool specimens of AFP patients using cell culture; and confirmed by the real time RT PCR intra-typic differentiation and vaccine-derived poliovirus assays. Seventy-nine (79) Sabin-like poliovirus 1 (SL1) and 86 Sabin-like poliovirus 3 (SL3) were sequenced. The VP1 amino acid substitutions T106A in Sabin poliovirus 1 and A54V in Sabin poliovirus 3 were common among the AFP patients as has been found in previous studies. Other substitutions that were associated with AFP were: T290A and A54T in SL1 and SL3 respectively. Nucleotide mutations that were common among the AFP patients included T402C, C670A, and T816C in SL1, and G22A, C375Y, A472R, and A694T in SL3 polioviruses. Characterizing mutations that are associated with AFP could contribute to efforts pursued to mitigate the risk of vaccine-derived polioviruses and promote development of safer vaccines.
Topics: Humans; Poliovirus; Uganda; alpha-Fetoproteins; Enterovirus; Poliomyelitis; Poliovirus Vaccine, Oral; Paralysis
PubMed: 37533043
DOI: 10.1186/s12985-023-02143-7