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Expert Review of Vaccines 2015The polio eradication endgame aims to bring transmission of all polioviruses to a halt. To achieve this aim, it is essential to block viral replication in individuals... (Review)
Review
The polio eradication endgame aims to bring transmission of all polioviruses to a halt. To achieve this aim, it is essential to block viral replication in individuals via induction of a robust mucosal immune response. Although it has long been recognized that inactivated poliovirus vaccine (IPV) is incapable of inducing a strong mucosal response on its own, it has recently become clear that IPV may boost immunity in the intestinal mucosa among individuals previously immunized with oral poliovirus vaccine. Indeed, mucosal protection appears to be stronger following a booster dose of IPV than oral poliovirus vaccine, especially in older children. Here, we review the available evidence regarding the impact of IPV on mucosal immunity, and consider the implications of this evidence for the polio eradication endgame. We conclude that the implementation of IPV in both routine and supplementary immunization activities has the potential to play a key role in halting poliovirus transmission, and thereby hasten the eradication of polio.
Topics: Disease Eradication; Disease Transmission, Infectious; Humans; Immunity, Mucosal; Poliomyelitis; Poliovirus Vaccine, Inactivated
PubMed: 26159938
DOI: 10.1586/14760584.2015.1052800 -
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 -
Lancet (London, England) Nov 2016
Topics: Antibodies, Viral; Humans; Immunization Schedule; Infant; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Poliovirus Vaccines
PubMed: 27871742
DOI: 10.1016/S0140-6736(16)32177-8 -
Risk Analysis : An Official Publication... Feb 2021The polio endgame remains complicated, with many questions about future polio vaccines and national immunization policies. We simulated possible future poliovirus...
The polio endgame remains complicated, with many questions about future polio vaccines and national immunization policies. We simulated possible future poliovirus vaccine routine immunization policies for countries stratified by World Bank Income Levels and estimated the expected costs and cases using an updated integrated dynamic poliovirus transmission, stochastic risk, and economic model. We consider two reference cases scenarios: one that achieves the eradication of all wild polioviruses (WPVs) by 2023 and one in which serotype 1 WPV (WPV1) transmission continues. The results show that the addition of inactivated poliovirus vaccine (IPV) to routine immunization in all countries substantially increased the expected costs of the polio endgame, without substantially increasing its expected health or economic benefits. Adding a second dose of IPV to the routine immunization schedules of countries that currently include a single IPV dose further increases costs and does not appear economically justified in the reference case that does not stop WPV transmission. For the reference case that includes all WPV eradication, adding a second IPV dose at the time of successful oral poliovirus vaccine (OPV) cessation represents a cost-effective option. The risks and costs of needing to restart OPV use change the economics of the polio endgame, although the time horizon used for modeling impacts the overall economic results. National health leaders will want to consider the expected health and economic net benefits of their national polio vaccine strategies recognizing that preferred strategies may differ.
Topics: Cost-Benefit Analysis; Economics, Medical; Global Health; Health Care Costs; Health Policy; Humans; Immunization; Models, Economic; Models, Theoretical; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Risk; Stochastic Processes
PubMed: 33590519
DOI: 10.1111/risa.13664 -
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 -
The Lancet. Infectious Diseases Oct 2019The eradication of wild and vaccine-derived poliovirus requires the global withdrawal of oral poliovirus vaccines (OPVs) and replacement with inactivated poliovirus... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
The eradication of wild and vaccine-derived poliovirus requires the global withdrawal of oral poliovirus vaccines (OPVs) and replacement with inactivated poliovirus vaccines (IPVs). The first phase of this effort was the withdrawal of the serotype 2 vaccine in April 2016, with a switch from trivalent OPVs to bivalent OPVs. The aim of our study was to produce comparative estimates of humoral and intestinal mucosal immunity associated with different routine immunisation schedules.
METHODS
We did a random-effect meta-analysis with single proportions and a network meta-analysis in a Bayesian framework to synthesise direct and indirect data. We searched MEDLINE and the Cochrane Library Central Register of Controlled Trials for randomised controlled trials published from Jan 1, 1980, to Nov 1, 2018, comparing poliovirus immunisation schedules in a primary series. Only trials done outside western Europe or North America and without variation in age schedules (ie, age at administration of the vaccine) between study groups were included in the analyses, because trials in high-income settings differ in vaccine immunogenicity and schedules from other settings and to ensure consistency within the network of trials. Data were extracted directly from the published reports. We assessed seroconversion against poliovirus serotypes 1, 2, and 3, and intestinal immunity against serotype 2, measured by absence of shedding poliovirus after a challenge OPV dose.
FINDINGS
We identified 437 unique studies; of them, 17 studies with a maximum of 8279 evaluable infants were eligible for assessment of humoral immunity, and eight studies with 4254 infants were eligible for intestinal immunity. For serotype 2, there was low between-trial heterogeneity in the data (τ=0·05, 95% credible interval [CrI] 0·009-0·15) and the risk ratio (RR) of seroconversion after three doses of bivalent OPVs was 0·14 (95% CrI 0·11-0·17) compared with three doses of trivalent OPVs. The addition of one or two full doses of an IPV after a bivalent OPV schedule increased the RR to 0·85 (0·75-1·0) and 1·1 (0·98-1·4). However, the addition of an IPV to bivalent OPV schedules did not significantly increase intestinal immunity (0·33, 0·18-0·61), compared with trivalent OPVs alone. For serotypes 1 and 3, there was susbstantial inconsistency and between-trial heterogeneity between direct and indirect effects, so we only present pooled estmates on seroconversion, which were at least 80% for serotype 1 and at least 88% for serotype 3 for all vaccine schedules.
INTERPRETATION
For WHO's polio eradication programme, the addition of one IPV dose for all birth cohorts should be prioritised to protect against paralysis caused by type 2 poliovirus; however, this inclusion will not prevent transmission or circulation in areas with faecal-oral transmission.
FUNDING
UK Medical Research Council.
Topics: Antibodies, Viral; Disease Eradication; Feces; Humans; Immunity, Humoral; Immunity, Mucosal; Immunization Schedule; Immunogenicity, Vaccine; Infant; Infant, Newborn; Intestinal Mucosa; Network Meta-Analysis; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Seroconversion; Serogroup; Vaccination; Virus Shedding
PubMed: 31350192
DOI: 10.1016/S1473-3099(19)30301-9 -
Vaccine Jun 2023Prior modeling studies showed that current outbreak management strategies are unlikely to stop outbreaks caused by type 1 wild polioviruses (WPV1) or circulating...
Prior modeling studies showed that current outbreak management strategies are unlikely to stop outbreaks caused by type 1 wild polioviruses (WPV1) or circulating vaccine-derived polioviruses (cVDPVs) in many areas, and suggested increased risks of outbreaks with cocirculation of more than one type of poliovirus. The surge of type 2 poliovirus transmission that began in 2019 and continues to date, in conjunction with decreases in preventive supplemental immunization activities (SIAs) for poliovirus types 1 and 3, has led to the emergence of several countries with cocirculation of more than one type of poliovirus. Response to these emerging cocirculation events is theoretically straightforward, but the different formulations, types, and inventories of oral poliovirus vaccines (OPVs) available for outbreak response present challenging practical questions. In order to demonstrate the implications of using different vaccine options and outbreak campaign strategies, we applied a transmission model to a hypothetical population with conditions similar to populations currently experiencing outbreaks of cVDPVs of both types 1 and 2. Our results suggest prevention of the largest number of paralytic cases occurs when using (1) trivalent OPV (tOPV) (or coadministering OPV formulations for all three types) until one poliovirus outbreak type dies out, followed by (2) using a type-specific OPV until the remaining poliovirus outbreak type also dies out. Using tOPV first offers a lower overall expected cost, but this option may be limited by the willingness to expose populations to type 2 Sabin OPV strains. For strategies that use type 2 novel OPV (nOPV2) concurrently administered with bivalent OPV (bOPV, containing types 1 and 3 OPV) emerges as a leading option, but questions remain about feasibility, logistics, type-specific take rates, and coadministration costs.
Topics: Humans; Disease Outbreaks; Global Health; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral
PubMed: 37121801
DOI: 10.1016/j.vaccine.2023.04.037 -
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