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Vaccine Mar 2023Inactivated trivalent poliovirus vaccine (IPV) induces humoral immunity, which protects against paralytic poliomyelitis but does not induce sufficient mucosal immunity... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety, tolerability, and immunogenicity of inactivated poliovirus vaccine with or without E.coli double mutant heat-labile toxin (dmLT) adjuvant in healthy adults; a phase 1 randomized study.
BACKGROUND
Inactivated trivalent poliovirus vaccine (IPV) induces humoral immunity, which protects against paralytic poliomyelitis but does not induce sufficient mucosal immunity to block intestinal infection. We assessed the intestinal immunity in healthy adults in Belgium conferred by a co-formulation of IPV with the mucosal adjuvant double mutant Labile Toxin (dmLT) derived from Escherichia coli.
METHODS
Healthy fully IPV-vaccinated 18-45-year-olds were randomly allocated to three groups: on Day 1 two groups received one full dose of IPV (n = 30) or IPV + dmLT (n = 30) in a blinded manner, and the third received an open-label dose of bivalent live oral polio vaccine (bOPV types 1 and 3, n = 20). All groups received a challenge dose of bOPV on Day 29. Participants reported solicited and unsolicited adverse events (AE) using study diaries. Mucosal immune responses were measured by fecal neutralization and IgA on Days 29 and 43, with fecal shedding of challenge viruses measured for 28 days. Humoral responses were measured by serum neutralizing antibody (NAb).
RESULTS
Solicited and unsolicited AEs were mainly mild-to-moderate and transient in all groups, with no meaningful differences in rates between groups. Fecal shedding of challenge viruses in both IPV groups exceeded that of the bOPV group but was not different between IPV and IPV + dmLT groups. High serum NAb responses were observed in both IPV groups, alongside modest levels of fecal neutralization and IgA.
CONCLUSIONS
Addition of dmLT to IPV administered intramuscularly neither affected humoral nor intestinal immunity nor decreased fecal virus shedding following bOPV challenge. The tolerability of the dose of dmLT used in this study may allow higher doses to be investigated for impact on mucosal immunity. Registered on ClinicalTrials.gov - NCT04232943.
Topics: Humans; Adult; Poliovirus Vaccine, Inactivated; Poliomyelitis; Hot Temperature; Poliovirus Vaccine, Oral; Adjuvants, Immunologic; Antibodies, Neutralizing; Immunoglobulin A
PubMed: 36746739
DOI: 10.1016/j.vaccine.2023.01.048 -
Plant Biotechnology Journal Nov 2016The WHO recommends complete withdrawal of oral polio vaccine (OPV) type 2 by April 2016 globally and replacing with at least one dose of inactivated poliovirus vaccine...
The WHO recommends complete withdrawal of oral polio vaccine (OPV) type 2 by April 2016 globally and replacing with at least one dose of inactivated poliovirus vaccine (IPV). However, high-cost, limited supply of IPV, persistent circulating vaccine-derived polioviruses transmission and need for subsequent boosters remain unresolved. To meet this critical need, a novel strategy of a low-cost cold chain-free plant-made viral protein 1 (VP1) subunit oral booster vaccine after single IPV dose is reported. Codon optimization of the VP1 gene enhanced expression by 50-fold in chloroplasts. Oral boosting of VP1 expressed in plant cells with plant-derived adjuvants after single priming with IPV significantly increased VP1-IgG1 and VP1-IgA titres when compared to lower IgG1 or negligible IgA titres with IPV injections. IgA plays a pivotal role in polio eradication because of its transmission through contaminated water or sewer systems. Neutralizing antibody titres (~3.17-10.17 log titre) and seropositivity (70-90%) against all three poliovirus Sabin serotypes were observed with two doses of IPV and plant-cell oral boosters but single dose of IPV resulted in poor neutralization. Lyophilized plant cells expressing VP1 stored at ambient temperature maintained efficacy and preserved antigen folding/assembly indefinitely, thereby eliminating cold chain currently required for all vaccines. Replacement of OPV with this booster vaccine and the next steps in clinical translation of FDA-approved antigens and adjuvants are discussed.
Topics: Chloroplasts; Communicable Diseases; Humans; Molecular Farming; Poliovirus Vaccine, Oral; Vaccination
PubMed: 27155248
DOI: 10.1111/pbi.12575 -
Vaccine Apr 2023Delivering inactivated poliovirus vaccine (IPV) with oral poliovirus vaccine (OPV) in campaigns has been explored to accelerate the control of type 2 circulating... (Review)
Review
Delivering inactivated poliovirus vaccine (IPV) with oral poliovirus vaccine (OPV) in campaigns has been explored to accelerate the control of type 2 circulating vaccine-derived poliovirus (cVDPV) outbreaks. A review of scientific literature suggests that among populations with high prevalence of OPV failure, a booster with IPV after at least two doses of OPV may close remaining humoral and mucosal immunity gaps more effectively than an additional dose of trivalent OPV. However, IPV alone demonstrates minimal advantage on humoral immunity compared with monovalent and bivalent OPV, and cannot provide the intestinal immunity that prevents infection and spread to those individuals not previously exposed to live poliovirus of the same serotype (i.e. type 2 for children born after the switch from trivalent to bivalent OPV in April 2016). A review of operational data from polio campaigns shows that addition of IPV increases the cost and logistic complexity of campaigns. As a result, campaigns in response to an outbreak often target small areas. Large campaigns require a delay to ensure logistics are in place for IPV delivery, and may need implementation in phases that last several weeks. Challenges to delivery of injectable vaccines through house-to-house visits also increases the risk of missing the children who are more likely to benefit from IPV: those with difficult access to routine immunization and other health services. Based upon this information, the Strategic Advisory Group of Experts in immunization (SAGE) recommended in October 2020 the following strategies: provision of a second dose of IPV in routine immunization to reduce the risk and number of paralytic cases in countries at risk of importation or new emergences; and use of type 2 OPV in high-quality campaigns to interrupt transmission and avoid seeding new type 2 cVDPV outbreaks.
Topics: Child; Humans; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Poliomyelitis; Disease Outbreaks
PubMed: 35365341
DOI: 10.1016/j.vaccine.2022.03.027 -
Human Vaccines & Immunotherapeutics Dec 2022Implementation of inactivated polio vaccines (IPV) containing Sabin strains (sIPV) will further enable global polio eradication efforts by improving vaccine safety... (Review)
Review
Implementation of inactivated polio vaccines (IPV) containing Sabin strains (sIPV) will further enable global polio eradication efforts by improving vaccine safety during use and containment during manufacturing. Moreover, sIPV-containing vaccines will lower costs and expand production capacity to facilitate more widespread use in low- and middle-income countries (LMICs). This review focuses on the role of vaccine formulation in these efforts including traditional Salk IPV vaccines and new sIPV-containing dosage forms. The physicochemical properties and stability profiles of poliovirus antigens are described. Formulation approaches to lower costs include developing multidose and combination vaccine formats as well as improving storage stability. Formulation strategies for dose-sparing and enhanced mucosal immunity include employing adjuvants (e.g. aluminum-salt and newer adjuvants) and/or novel delivery systems (e.g. ID administration with microneedle patches). The potential for applying these low-cost formulation development strategies to other vaccines to further improve vaccine access and coverage in LMICs is also discussed.
Topics: Humans; Poliovirus; Poliomyelitis; Poliovirus Vaccine, Inactivated; Adjuvants, Immunologic; Drug Delivery Systems; Poliovirus Vaccine, Oral; Antibodies, Viral
PubMed: 36576132
DOI: 10.1080/21645515.2022.2154100 -
Journal of Virology Sep 2018The poliovirus eradication initiative has spawned global immunization infrastructure and dramatically decreased the prevalence of the disease, yet the original virus...
The poliovirus eradication initiative has spawned global immunization infrastructure and dramatically decreased the prevalence of the disease, yet the original virus eradication goal has not been met. The suboptimal properties of the existing vaccines are among the major reasons why the program has repeatedly missed eradication deadlines. Oral live poliovirus vaccine (OPV), while affordable and effective, occasionally causes the disease in the primary recipients, and the attenuated viruses rapidly regain virulence and can cause poliomyelitis outbreaks. Inactivated poliovirus vaccine (IPV) is safe but expensive and does not induce the mucosal immunity necessary to interrupt virus transmission. While the need for a better vaccine is widely recognized, current efforts are focused largely on improvements to the OPV or IPV, which are still beset by the fundamental drawbacks of the original products. Here we demonstrate a different design of an antipoliovirus vaccine based on production of virus-like particles (VLPs). The poliovirus capsid protein precursor, together with a protease required for its processing, are expressed from a Newcastle disease virus (NDV) vector, a negative-strand RNA virus with mucosal tropism. In this system, poliovirus VLPs are produced in the cells of vaccine recipients and are presented to their immune systems in the context of active replication of NDV, which serves as a natural adjuvant. Intranasal administration of the vectored vaccine to guinea pigs induced strong neutralizing systemic and mucosal antibody responses. Thus, the vectored poliovirus vaccine combines the affordability and efficiency of a live vaccine with absolute safety, since no full-length poliovirus genome is present at any stage of the vaccine life cycle. A new, safe, and effective vaccine against poliovirus is urgently needed not only to complete the eradication of the virus but also to be used in the future to prevent possible virus reemergence in a postpolio world. Currently, new formulations of the oral vaccine, as well as improvements to the inactivated vaccine, are being explored. In this study, we designed a viral vector with mucosal tropism that expresses poliovirus capsid proteins. Thus, poliovirus VLPs are produced , in the cells of a vaccine recipient, and are presented to the immune system in the context of vector virus replication, stimulating the development of systemic and mucosal immune responses. Such an approach allows the development of an affordable and safe vaccine that does not rely on the full-length poliovirus genome at any stage.
Topics: Animals; Antibodies, Viral; Capsid Proteins; Genetic Vectors; Guinea Pigs; Immunity, Mucosal; Immunoglobulin A; Immunoglobulin G; Newcastle disease virus; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccines; Vaccination; Vaccines, Live, Unattenuated; Vaccines, Virus-Like Particle
PubMed: 29925653
DOI: 10.1128/JVI.00976-18 -
Archivos Argentinos de Pediatria Dec 2016Poliovirus infects 100% of susceptible individuals and causes acute flaccid paralysis in one out of200 infections. Type 1 causes epidemic poliomyelitis; type 2 has been...
Poliovirus infects 100% of susceptible individuals and causes acute flaccid paralysis in one out of200 infections. Type 1 causes epidemic poliomyelitis; type 2 has been eradicated worldwide; and type 3 is close to being eradicated. In this region, the last case of wild poliovirus occurred in Peru in 1991. There are still two endemic countries: Afghanistan and Pakistan, but countries where there is no circulation of the wild poliovirus have also reported imported cases of polio. In May 2012, the World Health Assembly declared the polio eradication a programmatic emergency for global public health and, as a result, developed the Polio Eradication and Endgame Strategic Plan 2013-2018. The Plan has four objectives: 1) Detect and interrupt all poliovirus transmission and maintain surveillance of acute flaccid paralysis in children < 15 years. 2) Strengthen immunization systems and withdraw oral polio vaccine by the first trimester of 2016. Replace the trivalent oral polio vaccine with the bivalent oral vaccine, containing serotypes 1 and 3, and introduce the inactivated polio vaccine in all immunization schedules to maintain immunity against poliovirus type 2. 3) Contain poliovirus and certify interruption of transmission. 4) Plan the exploitation of the fight against polio and its impact on public health. The plan is expected to reach its goals by 2018; all use of the oral polio vaccine will be interrupted thereafter. Change in immunization schedules will require pediatricians to provide advice and guidance to families depending on the varied situations of everyday practice.
Topics: Adolescent; Child; Disease Eradication; Global Health; Humans; Immunization Schedule; Poliomyelitis; Poliovirus Vaccine, Oral; Poliovirus Vaccines; Time Factors
PubMed: 27869415
DOI: 10.5546/aap.2016.eng.557 -
Nature Communications Jun 2023Increasing detections of vaccine-derived poliovirus (VDPV) globally, including in countries previously declared polio free, is a public health emergency of international...
Increasing detections of vaccine-derived poliovirus (VDPV) globally, including in countries previously declared polio free, is a public health emergency of international concern. Individuals with primary immunodeficiency (PID) can excrete polioviruses for prolonged periods, which could act as a source of cryptic transmission of viruses with potential to cause neurological disease. Here, we report on the detection of immunodeficiency-associated VDPVs (iVDPV) from two asymptomatic male PID children in the UK in 2019. The first child cleared poliovirus with increased doses of intravenous immunoglobulin, the second child following haematopoetic stem cell transplantation. We perform genetic and phenotypic characterisation of the infecting strains, demonstrating intra-host evolution and a neurovirulent phenotype in transgenic mice. Our findings highlight a pressing need to strengthen polio surveillance. Systematic collection of stool from asymptomatic PID patients who are at high risk for poliovirus excretion could improve the ability to detect and contain iVDPVs.
Topics: Animals; Male; Mice; Immunologic Deficiency Syndromes; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; United Kingdom
PubMed: 37296153
DOI: 10.1038/s41467-023-39094-0 -
Biologicals : Journal of the... May 2018According to manufacturers, inactivated poliovirus vaccines (IPVs) are freeze sensitive and require storage between 2°C and 8°C, whereas oral poliovirus vaccine...
According to manufacturers, inactivated poliovirus vaccines (IPVs) are freeze sensitive and require storage between 2°C and 8°C, whereas oral poliovirus vaccine requires storage at -20 °C. Introducing IPV into ongoing immunization services might result in accidental exposure to freezing temperatures and potential loss of vaccine potency. To better understand the effect of freezing IPVs, samples of single-dose vaccine vials from Statens Serum Institut (VeroPol) and multi-dose vaccine vials from Sanofi Pasteur (IPOL) were exposed to freezing temperatures mimicking what a vaccine vial might encounter in the field. D-antigen content was measured to determine the in vitro potency by ELISA. Immunogenicity testing was conducted for a subset of exposed IPVs using the rat model. Freezing VeroPol had no detectable effect on in vitro potency (D-antigen content) in all exposures tested. Freezing of the IPOL vaccine for 7 days at -20 °C showed statistically significant decreases in D-antigen content by ELISA in poliovirus type 1 (p < 0.0001) and type 3 (p = 0.048). Reduction of poliovirus type 2 potency also approached significance (p = 0.062). The observed loss in D-antigen content did not affect immunogenicity in the rat model. Further work is required to determine the significance of the loss observed and the implications for vaccine handling policies and practices.
Topics: Animals; Cryopreservation; Female; Freezing; Immunogenicity, Vaccine; Poliovirus Vaccine, Inactivated; Rats; Rats, Wistar
PubMed: 29548791
DOI: 10.1016/j.biologicals.2018.03.002 -
Human Vaccines & Immunotherapeutics Dec 2022As one of the powerful vaccines for completely eradicating all types of poliovirus in the polio endgame period, the novel IPV, which is prepared from attenuated polio...
As one of the powerful vaccines for completely eradicating all types of poliovirus in the polio endgame period, the novel IPV, which is prepared from attenuated polio Sabin strains (sIPV) and is expected to reduce the overall biosafety risk, was licensed in Japan (sIPV-containing diphtheria-tetanus-acellular pertussis combination vaccines, DTP-sIPV) and China (sIPV) in November 2012 and January 2015, respectively. Limited by the development progress and the manufactured sIPV ability, it has to date only been used in Chinese Expanded Programme on Immunization (EPI) by sequential scheduling with bOPV and in Japan with DTP-sIPV vaccination. We herein summarize postapproval clinical studies of sIPV in both full-dose schedules and sequential schedules, focusing on China, to evaluate sIPV safety and immunogenicity in large populations to provide important data for its broad application in developing countries worldwide.
Topics: Antibodies, Viral; Diphtheria-Tetanus-Pertussis Vaccine; Diphtheria-Tetanus-acellular Pertussis Vaccines; Humans; Immunization Schedule; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated
PubMed: 34213408
DOI: 10.1080/21645515.2021.1940653 -
Journal of Clinical Microbiology Jul 2017Oral poliovirus vaccine can mutate to regain neurovirulence. To date, evaluation of these mutations has been performed primarily on culture-enriched isolates by using...
Oral poliovirus vaccine can mutate to regain neurovirulence. To date, evaluation of these mutations has been performed primarily on culture-enriched isolates by using conventional Sanger sequencing. We therefore developed a culture-independent, deep-sequencing method targeting the 5' untranslated region (UTR) and P1 genomic region to characterize vaccine-related poliovirus variants. Error analysis of the deep-sequencing method demonstrated reliable detection of poliovirus mutations at levels of <1%, depending on read depth. Sequencing of viral nucleic acids from the stool of vaccinated, asymptomatic children and their close contacts collected during a prospective cohort study in Veracruz, Mexico, revealed no vaccine-derived polioviruses. This was expected given that the longest duration between sequenced sample collection and the end of the most recent national immunization week was 66 days. However, we identified many low-level variants (<5%) distributed across the 5' UTR and P1 genomic region in all three Sabin serotypes, as well as vaccine-related viruses with multiple canonical mutations associated with phenotypic reversion present at high levels (>90%). These results suggest that monitoring emerging vaccine-related poliovirus variants by deep sequencing may aid in the poliovirus endgame and efforts to ensure global polio eradication.
Topics: Child, Preschool; Feces; Female; Genetic Variation; High-Throughput Nucleotide Sequencing; Humans; Infant; Male; Mexico; Mutation; Poliovirus; Poliovirus Vaccine, Oral; Prospective Studies
PubMed: 28468861
DOI: 10.1128/JCM.00144-17