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Vaccine Apr 2023
Topics: Humans; Poliovirus; Poliovirus Vaccine, Oral; Poliomyelitis; Vaccination; Disease Outbreaks; Poliovirus Vaccine, Inactivated; Global Health
PubMed: 36907735
DOI: 10.1016/j.vaccine.2023.02.082 -
Human Vaccines & Immunotherapeutics May 2021This first-in-human study (NCT03032588), conducted in Belgium, evaluated a new inactivated poliovirus vaccines (IPV) candidate based on Sabin poliovirus strains grown on... (Randomized Controlled Trial)
Randomized Controlled Trial
This first-in-human study (NCT03032588), conducted in Belgium, evaluated a new inactivated poliovirus vaccines (IPV) candidate based on Sabin poliovirus strains grown on the high-yield PER.C6® cell line. Healthy adults (N = 32) were randomized (1:1) to receive a single dose of PER.C6-based Sabin-IPV (sIPV, 15:35:112.5 DU/dose) or conventional Salk-IPV (cIPV, 40:8:32 DU/dose). Reactogenicity was assessed up to 7 days after vaccination, immunogenicity 28 days after vaccination, and safety up to 6 months after vaccination.Solicited adverse events (AEs) were mild to moderate, no changes of concern in vital signs or safety laboratory values were observed, and no severe AEs (SAEs) or vaccine-related unsolicited AEs were reported after vaccination. A trend to more frequent solicited AEs after sIPV than after cIPV administration was observed. Most participants had preexisting neutralizing antibodies against poliovirus types (titer ≥8), which were strongly boosted by sIPV. Post-vaccination geometric mean titers were high (≥12,000) and similar across the two vaccination groups. Only participants with very high preexisting antibody levels did not show a vaccine-induced response, defined in seropositive participants as a 4-fold titer increase. The 10 initially seronegative (titer <8) participants (n = 5 in each study group) seroconverted and all participants had seroprotective antibody levels post-vaccination. The antibodies elicited by sIPV neutralized both Sabin and Salk poliovirus strains.In conclusion, the PER.C6®-based sIPV was well tolerated and highly immunogenic in adults with preexisting antibodies to poliovirus.
Topics: Adult; Antibodies, Viral; Belgium; Cell Line; Humans; Immunogenicity, Vaccine; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral
PubMed: 33175637
DOI: 10.1080/21645515.2020.1812315 -
Journal of Immunological Methods May 2022Next generation poliovirus vaccines are critical to reaching global poliovirus eradication goals. Recent efforts have focused on creating inactivated vaccines using...
Next generation poliovirus vaccines are critical to reaching global poliovirus eradication goals. Recent efforts have focused on creating inactivated vaccines using attenuated Sabin strains that maintain patient safety benefits and immunogenicity of conventional inactivated vaccines while increasing manufacturing safety and lowering production costs, and on developing novel oral vaccines using modified Sabin strains that provide critical mucosal immunity but are further attenuated to minimize risk of reversion to neurovirulence. In addition, there is a push to improve the analytical tools for poliovirus vaccine characterization. Conventional and Sabin inactivated poliovirus vaccines typically rely on standard plate-based ELISA as in vitro D-antigen potency assays in combination with WHO international standards as calibrants. While widely utilized, the current D-antigen ELISA assays have a long time to result (up to 72 h), can suffer from lab-to-lab inconsistency due to non-standardized protocols and reagents, and are inherently singleplex. For D-antigen quantitation, we have developed the VaxArray Polio Assay Kit, a multiplexed, microarray-based immunoassay that uses poliovirus-specific human monoclonal antibodies currently under consideration as standardized reagents for characterizing inactivated Sabin and Salk vaccines. The VaxArray assay can simultaneously quantify all 3 poliovirus serotypes with a time to result of less than 3 h. Here we demonstrate that the assay has limits of quantification suitable for both bioprocess samples and final vaccines, excellent reproducibility and precision, and improved accuracy over an analogous plate-based ELISA. The assay is suitable for adjuvanted combination vaccines, as common vaccine additives and crude matrices do not interfere with quantification, and is intended as a high throughput, standardized quantitation tool to aid inactivated poliovirus vaccine manufacturers in streamlining vaccine development and manufacturing, aiding the global polio eradication effort.
Topics: Antibodies, Viral; Antigens, Viral; Enzyme-Linked Immunosorbent Assay; Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Reproducibility of Results; Vaccines, Inactivated
PubMed: 35314144
DOI: 10.1016/j.jim.2022.113259 -
Expert Review of Vaccines 2023Hexaxim is a hexavalent vaccine approved as primary and booster vaccination in infants 6 weeks and older, protecting against diphtheria, tetanus, pertussis,... (Review)
Review
INTRODUCTION
Hexaxim is a hexavalent vaccine approved as primary and booster vaccination in infants 6 weeks and older, protecting against diphtheria, tetanus, pertussis, poliomyelitis, hepatitis B and Haemophilus influenzae type b.
AREAS COVERED
To evaluate the immunogenicity and reactogenicity (safety) of Hexaxim (Hexyon, Hexacima) in primary and booster vaccine schedules; long-term antibody persistence; concomitant use with other childhood vaccines and use in immunocompromised infants. Hexaxim was found to be noninferior to other licensed hexavalent vaccines, being highly immunogenic for all toxoids/antigens and with an acceptable safety profile. It can be administered concomitantly with other childhood vaccines. Hexaxim can be given as a booster for infants primed with Infanrix Hexa and given in a pentavalent-hexavalent-pentavalent series. Hexaxim elicits a similar immune response and safety profile in human immunodeficiency virus (HIV) positive infants. It has the benefit of being a ready-to-use liquid formulation, minimizing dosage errors and preparation time.
EXPERT OPINION
Hexaxim has an acceptable safety profile and provides immunity against all six targeted diseases. It is an acceptable alternative to other hexavalent vaccines on the market. Further studies are required on the use of immunocompromised patients as well as the antibody persistence of each of the vaccine components.
Topics: Infant; Humans; Child; Immunization, Secondary; Immunization Schedule; Diphtheria-Tetanus-Pertussis Vaccine; Haemophilus Vaccines; Poliovirus Vaccine, Inactivated; Hepatitis B Vaccines; Vaccines, Combined; Antibodies, Bacterial
PubMed: 36545777
DOI: 10.1080/14760584.2023.2161519 -
Vaccine Oct 2021Afghanistan is one of two countries with endemic wild poliovirus type 1 (WPV1). The oral poliovirus vaccine (OPV) is the predominant vaccine used for polio eradication....
BACKGROUND
Afghanistan is one of two countries with endemic wild poliovirus type 1 (WPV1). The oral poliovirus vaccine (OPV) is the predominant vaccine used for polio eradication. Although OPV has been administered in routine childhood immunization and during frequent supplementary immunization activities, WPV1 continues to circulate in Afghanistan and case incidence has been increasing since 2017. We estimated the effectiveness of OPV in Afghanistan during 2010-2020.
METHODS
We conducted a matched case-control analysis using acute flaccid paralysis (AFP) surveillance data from 29,370 children < 15 years with AFP onset between January 1, 2010 and December 31, 2020. We matched children with confirmed WPV1 (cases) with children with non-polio AFP (controls) by age at onset of paralysis (+/- 3 months), date of onset of paralysis (+/- 3 months), and province of residence, and compared their reported OPV vaccination history to estimate the effectiveness of OPV in preventing paralysis by WPV1 using conditional logistic regression. To account for changes in OPV formulations provided over the analysis period, we stratified the analysis based on dates of the global switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) in April 2016.
RESULTS
Between January 1, 2010 and December 31, 2020, there were 329 WPV1 cases in Afghanistan. The per-dose estimated effectiveness of OPV against WPV1 was 19% (95% CI: 15%-22%) and of ≥ 7 doses was 94% (95% CI: 90%-97%). Before the global switch from tOPV to bOPV, the per-dose estimated effectiveness of OPV was 14% (95% CI: 11%-18%) and of ≥ 7 doses was 92% (95% CI: 85%-96%). After the switch, the per-dose estimated effectiveness of OPV against WPV1 was 32% (24%-39%) and of ≥ 7 doses was 96% (95% CI: 90%-99%).
DISCUSSION
OPV is highly effective in preventing paralysis by WPV1; these results indicate that continued WPV1 transmission in Afghanistan is due to failure to vaccinate, not failure of the vaccine. Although difficult to implement in parts of country, improving the administration of OPV in routine immunization and supplementary immunization activities will be critical for achieving polio eradication in Afghanistan.
Topics: Afghanistan; Child; Disease Eradication; Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral
PubMed: 34538696
DOI: 10.1016/j.vaccine.2021.09.020 -
Journal of Medical Virology Mar 2023Polio cases can be missed by acute flaccid paralysis (AFP) case surveillance alone, emphasizing the importance of environmental surveillance (ES). In this study, to...
Polio cases can be missed by acute flaccid paralysis (AFP) case surveillance alone, emphasizing the importance of environmental surveillance (ES). In this study, to investigate the serotype distribution and epidemiological trends of poliovirus (PV), we characterized PV isolated from domestic sewage in Guangzhou City, Guangdong Province, China from 2009 to 2021. A total of 624 sewage samples were collected from the Liede Sewage Treatment Plant, and the positive rates of PV and non-polio enteroviruses were 66.67% (416/624) and 78.37% (489/624), respectively. After sewage sample treatment, each sewage sample was inoculated in six replicate tubes of three cell lines, and 3370 viruses were isolated during the 13-year surveillance period. Among these, 1086 isolates were identified as PV, including type 1 PV (21.36%), type 2 PV (29.19%), and type 3 PV (49.48%). Based on VP1 sequences, 1057 strains were identified as Sabin-like, 21 strains were high-mutant vaccines, and eight strains were vaccine-derived poliovirus (VDPV). The numbers and serotypes of PV isolates in sewage were influenced by the vaccine switch strategy. After type 2 OPV was removed from the trivalent oral PV (OPV) vaccine and a bivalent OPV (bOPV) was adopted in May 2016, the last type 2 PV strain was isolated from sewage, with no detection thereafter. Type 3 PV isolates increased significantly and became the dominant serotype. Before and after the second vaccine switch in January 2020, that is, from the first dose of IPV and second-fourth doses of bOPV to the first two doses of IPV and third-fourth doses of bOPV, there was also a statistical difference in PV positivity rates in sewage samples. Seven type 2 VDPVs and one type 3 VDPV were identified in sewage samples in 2009-2021, and phylogenetic analysis indicated that all VDPVs isolated from ES in Guangdong are newly discovered VDPVs, different from VDPV previously discovered in China, and were classified as ambiguous VDPV. It is noteworthy that no VDPV cases were reported in AFP case surveillance in the same period. In conclusion, continued PV ES in Guangzhou since April 2008 has been a useful supplement to AFP case surveillance, providing an important basis for evaluating the effectiveness of vaccine immunization strategies. ES improves early detection, prevention, and control; accordingly, this strategy can curb the circulation of VDPVs and provide a strong laboratory basis for maintaining a polio-free status.
Topics: Humans; Poliovirus; Sewage; Phylogeny; alpha-Fetoproteins; Poliovirus Vaccine, Oral; Poliomyelitis; Environmental Monitoring
PubMed: 36905116
DOI: 10.1002/jmv.28668 -
Biologicals : Journal of the... Jul 2022Possible applicability of controlled temperature chain (CTC) for selected antisera and vaccines was evaluated. Bivalent oral polio vaccine (OPV), hepatitis B vaccine...
Antivenoms, hepatitis B vaccine and oral polio vaccine can be considered for storage and handling outside the cold chain following the innovative 'controlled temperature chain' approach.
Possible applicability of controlled temperature chain (CTC) for selected antisera and vaccines was evaluated. Bivalent oral polio vaccine (OPV), hepatitis B vaccine (HepB vaccine; monovalent and combined) and antisera (lyophilized and liquid scorpion-antivenom and liquid snake-antivenom) were tested. Samples were stored at accelerated (35 ± 5 °C) and freezing (-25 ± 5 °C) conditions for 24 h, one week and one month in addition to recommended storage condition (2-8 °C), except OPV samples that were tested at accelerated and refrigerated (2-8 °C) conditions compared to recommended storage conditions (-25 ± 5 °C). All samples were tested for potency. Protein content and composition were determined for antisera samples. All vaccine vial-monitors were evaluated. HepB vaccine was subjected to aluminum-content assay, shake test and microscopical examination. No significant change in antisera potency was detectable under accelerated condition for a week. OPV stored in refrigerator for a month and at accelerated condition for 48 h maintained acceptable potency. Monovalent and combined HepB vaccine maintained acceptable potency under accelerated condition for a month and a week, respectively. Freezing adversely affected HepB vaccine. In conclusion, reevaluation of storage conditions of tested products is urgently required; this can reduce storage costs and improves their availability. Other products should be tested for possible CTC applicability.
Topics: Antivenins; Drug Storage; Hepatitis B Vaccines; Humans; Phenylbutyrates; Poliomyelitis; Poliovirus Vaccine, Oral; Refrigeration; Temperature
PubMed: 35803876
DOI: 10.1016/j.biologicals.2022.06.002 -
Medical Decision Making : An... 2023Polio antiviral drugs (PAVDs) may provide a critical tool in the eradication endgame by stopping poliovirus infections in immunodeficient individuals who may not clear...
BACKGROUND
Polio antiviral drugs (PAVDs) may provide a critical tool in the eradication endgame by stopping poliovirus infections in immunodeficient individuals who may not clear the virus without therapeutic intervention. Although prolonged/chronic poliovirus excreters are rare, they represent a source of poliovirus reintroduction into the general population. Prior studies that assumed the successful cessation of all oral poliovirus vaccine (OPV) use estimated the potential upper bound of the incremental net benefits (INBs) of resource investments in research and development of PAVDs. However, delays in polio eradication, OPV cessation, and the development of PAVDs necessitate an updated economic analysis to reevaluate the costs and benefits of further investments in PAVDs.
METHODS
Using a global integrated model of polio transmission, immunity, vaccine dynamics, risks, and economics, we explore the risks of reintroduction of polio transmission due to immunodeficiency-related vaccine-derived poliovirus (iVDPV) excreters and reevaluate the upper bound of the INBs of PAVDs.
RESULTS
Under the current conditions, for which the use of OPV will likely continue for the foreseeable future, even with successful eradication of type 1 wild poliovirus by the end of 2023 and continued use of Sabin OPV for outbreak response, we estimate an upper bound INB of 60 million US$2019. With >100 million US$2019 already invested in PAVD development and with the introduction of novel OPVs that are less likely to revert to neurovirulence, our analysis suggests the expected INBs of PAVDs would not offset their costs.
CONCLUSIONS
While PAVDs could play an important role in the polio endgame, their expected economic benefits drop with ongoing OPV use and poliovirus transmissions. However, stakeholders may pursue the development of PAVDs as a desired product regardless of their economic benefits.HighlightsWhile polio antiviral drugs could play an important role in the polio endgame, their expected economic benefits continue to drop with delays in polio eradication and the continued use of oral poliovirus vaccines.The incremental net benefits of investments in polio antiviral drug development and screening for immunodeficiency-related circulating polioviruses are small.Limited global resources are better spent on increasing global population immunity to polioviruses to stop and prevent poliovirus transmission.
Topics: Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Disease Outbreaks; Antiviral Agents
PubMed: 37577803
DOI: 10.1177/0272989X231191127 -
PloS One 2024Polio eradication is a current and common strategy throughout the globe. The study of the newly introduced inactivated poliovirus vaccine provides a grasp on the current...
INTRODUCTION
Polio eradication is a current and common strategy throughout the globe. The study of the newly introduced inactivated poliovirus vaccine provides a grasp on the current status of immunization and identifies any disparities in the implementation of the vaccine throughout Ethiopia. Thus, this study aimed to demonstrate the spatial distribution, coverage, and determinants of inactivated poliovirus vaccine immunization in Ethiopia.
METHOD
Spatial distribution and determinants of inactivated poliovirus vaccine immunization in Ethiopia were conducted using Ethiopian mini-demographic and health survey 2019 data. A total of 2,056 weighted children aged 12 to 35 months were included in the analysis. The association between the outcome and explanatory variables was determined by commuting the adjusted odds ratio at a 95% confidence interval. The p-value of less than 0.05 was used to declare factors as significantly associated with the inactivated poliovirus vaccine immunization.
RESULT
The weighted national coverage of inactivated poliovirus vaccine immunization in Ethiopia was 51.58% at a 95% confidence interval (49.42, 53.74). While the rates of inactivated poliovirus vaccine immunization were observed to be greater in Addis Ababa, Tigiray, Amahara, and Benishangul Gumuz provinces and lower in the Somali, Afar, and SNNPR provinces of Ethiopia, Antenatal care follow-up, place of delivery, place of residence, and region were significantly associated with inactivated poliovirus immunization in Ethiopia.
CONCLUSION
The distribution of inactivated poliovirus immunization was spatially variable across Ethiopia. Only about half of the children aged twelve to thirty-five months received the inactivated poliovirus vaccine in the country. The factors, both at the individual and community level, were significantly associated with inactivated poliovirus immunization. Therefore, policies and strategies could benefit from considering antenatal care follow-up, place of delivery, place of residence, and region while implementing inactivated poliovirus vaccine immunization.
Topics: Humans; Ethiopia; Poliovirus Vaccine, Inactivated; Female; Infant; Poliomyelitis; Male; Child, Preschool; Vaccination Coverage; Vaccination; Immunization Programs; Immunization
PubMed: 38820454
DOI: 10.1371/journal.pone.0301933 -
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