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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 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 -
MMWR. Morbidity and Mortality Weekly... Dec 2021As of May 1, 2016, use of oral poliovirus vaccine (OPV) type 2 for routine and supplementary immunization activities ceased after a synchronized global switch from...
As of May 1, 2016, use of oral poliovirus vaccine (OPV) type 2 for routine and supplementary immunization activities ceased after a synchronized global switch from trivalent OPV (tOPV; containing Sabin strain types 1, 2, and 3) to bivalent OPV (bOPV; containing Sabin strain types 1 and 3) subsequent to the certified eradication of wild type poliovirus (WPV) type 2 in 2015 (1-3). Circulating vaccine-derived poliovirus (cVDPV) outbreaks* occur when transmission of Sabin strain poliovirus is prolonged in underimmunized populations, allowing viral genetic reversion to neurovirulence, resulting in cases of paralytic polio (1-3). Since the switch, monovalent OPV type 2 (mOPV2, containing Sabin strain type 2) has been used for response to cVDPV type 2 (cVDPV2) outbreaks; tOPV is used if cVDPV2 co-circulates with WPV type 1, and bOPV is used for cVDPV type 1 (cVDPV1) or type 3 (cVDPV3) outbreaks (1-4). In November 2020, the World Health Organization (WHO) Emergency Use Listing procedure authorized limited use of type 2 novel OPV (nOPV2), a vaccine modified to be more genetically stable than the Sabin strain, for cVDPV2 outbreak response (3,5). In October 2021, the Strategic Advisory Group of Experts on Immunization (WHO's principal advisory group) permitted wider use of nOPV2; however, current nOPV2 supply is limited (6). This report updates that of July 2019-February 2020 to describe global cVDPV outbreaks during January 2020-June 2021 (as of November 9, 2021) (3). During this period, there were 44 cVDPV outbreaks of the three serotypes affecting 37 countries. The number of cVDPV2 cases increased from 366 in 2019 to 1,078 in 2020 (7). A goal of the Global Polio Eradication Initiative's (GPEI) 2022-2026 Strategic Plan is to better address the challenges to early CVDPV2 outbreak detection and initiate prompt and high coverage outbreak responses with available type 2 OPV to interrupt transmission by the end of 2023 (8).
Topics: Disease Outbreaks; Global Health; Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Serotyping
PubMed: 34882653
DOI: 10.15585/mmwr.mm7049a1 -
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 -
The Lancet. Infectious Diseases Feb 2022Expanding outbreaks of circulating vaccine-derived type 2 poliovirus (cVDPV2) across Africa after the global withdrawal of trivalent oral poliovirus vaccine (OPV) in...
Risk factors for the spread of vaccine-derived type 2 polioviruses after global withdrawal of trivalent oral poliovirus vaccine and the effects of outbreak responses with monovalent vaccine: a retrospective analysis of surveillance data for 51 countries in Africa.
BACKGROUND
Expanding outbreaks of circulating vaccine-derived type 2 poliovirus (cVDPV2) across Africa after the global withdrawal of trivalent oral poliovirus vaccine (OPV) in 2016 are delaying global polio eradication. We aimed to assess the effect of outbreak response campaigns with monovalent type 2 OPV (mOPV2) and the addition of inactivated poliovirus vaccine (IPV) to routine immunisation.
METHODS
We used vaccination history data from children under 5 years old with non-polio acute flaccid paralysis from a routine surveillance database (the Polio Information System) and setting-specific OPV immunogenicity data from the literature to estimate OPV-induced and IPV-induced population immunity against type 2 poliomyelitis between Jan 1, 2015, and June 30, 2020, for 51 countries in Africa. We investigated risk factors for reported cVDPV2 poliomyelitis including population immunity, outbreak response activities, and correlates of poliovirus transmission using logistic regression. We used the model to estimate cVDPV2 risk for each 6-month period between Jan 1, 2016, and June 30, 2020, with different numbers of mOPV2 campaigns and compared the timing and location of actual mOPV2 campaigns and the number of mOPV2 campaigns required to reduce cVDPV2 risk to low levels.
FINDINGS
Type 2 OPV immunity among children under 5 years declined from a median of 87% (IQR 81-93) in January-June, 2016 to 14% (9-37) in January-June, 2020. Type 2 immunity from IPV among children under 5 years increased from 3% (<1-6%) in January-June, 2016 to 35% (24-47) in January-June, 2020. The probability of cVDPV2 poliomyelitis among children under 5 years was negatively correlated with OPV-induced and IPV-induced immunity and mOPV2 campaigns (adjusted odds ratio: OPV 0·68 [95% CrI 0·60-0·76], IPV 0·82 [0·68-0·99] per 10% absolute increase in estimated population immunity, mOPV2 0·30 [0·20-0·44] per campaign). Vaccination campaigns in response to cVDPV2 outbreaks have been smaller and slower than our model shows would be necessary to reduce risk to low levels, covering only 11% of children under 5 years who are predicted to be at risk within 6 months and only 56% within 12 months.
INTERPRETATION
Our findings suggest that as mucosal immunity declines, larger or faster responses with vaccination campaigns using type 2-containing OPV will be required to stop cVDPV2 transmission. IPV-induced immunity also has an important role in reducing the burden of cVDPV2 poliomyelitis in Africa.
FUNDING
Bill & Melinda Gates Foundation, Medical Research Council Centre for Global Infectious Disease Analysis, and WHO.
TRANSLATION
For the French translation of the abstract see Supplementary Materials section.
Topics: Child; Child, Preschool; Disease Outbreaks; Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Retrospective Studies; Risk Factors
PubMed: 34648733
DOI: 10.1016/S1473-3099(21)00453-9 -
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 -
The Lancet. Infectious Diseases Aug 2021Since WHO recommended introduction of at least a single dose of inactivated poliovirus vaccine (IPV) in routine immunisation schedules, there have been global IPV... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Since WHO recommended introduction of at least a single dose of inactivated poliovirus vaccine (IPV) in routine immunisation schedules, there have been global IPV shortages. Fractional-dose IPV (fIPV) administration is one of the strategies to ensure IPV availability. We reviewed studies comparing the effects of fractional with full-dose IPV vaccination to determine when seroconversion proportions with each strategy become similar in children aged 5 years and younger.
METHOD
In this systematic review and meta-analysis, we searched 16 databases in July, 2019, for trials and observational studies, including ongoing studies that compare immunogenicity and adverse events of fractional-dose (0·1 mL) to full-dose (0·5 mL) IPV in healthy children aged 5 years or younger regardless of study design, number of doses, and route of administration. Screening, selection of articles, data extraction, and risk of bias assessment were done in duplicate, and conflicts were resolved by discussion or arbitration by a third author. We assessed immunogenicity, the main outcome, as proportion of seroconverted participants and changes in geometric mean titres of anti-poliovirus antibodies. Timepoints were eligible for analysis if measurements were done at least 4 weeks after vaccination. Summary estimates were pooled by use of random-effects meta-analysis. Analysis was stratified by study design, type of outcome measure, type of poliovirus, and number of doses given. We assessed heterogeneity using the χ test of homogeneity and quantified it using the I statistic. We assessed risk of bias using the Cochrane risk of bias tool, and the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. The study is registered with PROSPERO, CRD42018092647.
FINDINGS
860 records were screened for eligibility, of which 36 potentially eligible full-text articles were assessed and 14 articles were included in the final analysis: two ongoing trials and 12 articles reporting on ten completed studies. For poliovirus type 2, there were no significant differences in the proportions of seroconversions between fractional and full doses of IPV for two or three doses: the risk ratio for serconversion at one dose was 0·61 (95% CI 0·51-0·72), at two doses was 0·90 (0·82-1·00), and at three doses was 0·95 (0·91-1·00). Geometric mean titres (GMTs) for poliovirus type 2 were lower for fIPV than for full-dose IPV: -0·51 (95% CI -0·87 to -0·14) at one dose, -0·49 (-0·70 to -0·28) at two doses, and -0·98 (-1·46 to -0·51) at three doses. The seroconversion meta-analysis for the three-dose comparison was homogeneous (p=0·45; I=0%), whereas heterogeneity was observed in the two-dose (p<0·00001; I=88%) and one-dose (p=0·0004; I=74%) comparisons. Heterogeneity was observed in meta-analyses of GMTs for one-dose (p<0·00001; I=92%), two-dose (p=0·002; I=80%), and three-dose (p<0·00001; I=93%) comparisons. Findings for types 1 and 3 were similar to those for type 2. The certainty of the evidence was high for the three-dose comparisons and moderate for the rest of the comparisons.
INTERPRETATION
There is no substantial difference in seroconversion between three doses of fIPV and three doses of full-dose IPV, although the full dose gives higher titres of antibodies for poliovirus type 1, 2, and 3. Use of fractional IPV instead of the full dose can stretch supplies and possibly lower the cost of vaccination.
FUNDING
South African Medical Research Council and the National Research Foundation of South Africa.
Topics: Administration, Oral; Antibodies, Viral; Child, Preschool; Dose-Response Relationship, Immunologic; Humans; Immunization Schedule; Immunogenicity, Vaccine; Injections, Intradermal; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Randomized Controlled Trials as Topic; Seroconversion
PubMed: 33939958
DOI: 10.1016/S1473-3099(20)30693-9 -
Expert Review of Vaccines Feb 2020: Across Europe, immunization programs have brought immense benefits to the prevention of infectious diseases. The vaccines used are procured through a variety of models... (Review)
Review
: Across Europe, immunization programs have brought immense benefits to the prevention of infectious diseases. The vaccines used are procured through a variety of models such as tenders and Pricing & Reimbursement. However, to date, the impact of the procurement method on the performance and sustainability of vaccination programs and on public health has received little attention.: Drawing on a review of the academic and policy literature, complemented by an interview program with stakeholders involved in the procurement of vaccines, the authors have documented the relationship between procurement method dynamics and the level of protection against vaccine-preventable diseases in Germany, Italy, Spain and Romania for, measles-containing vaccines, hexavalent and influenza vaccines.: Price-based tenders can contribute to vaccine supply issues, discourage the provision of value-added services supporting vaccination coverage and disincentives future R&D. Although it is observed that price-based tenders can intensify competition in the short term, there can be unintended consequences such as damage to long-term competition. As European countries are committed to strengthen their immunization programs, they should consider the implications of current vaccine procurement models on the vaccine ecosystem and on public health.
Topics: Diphtheria-Tetanus-Pertussis Vaccine; Europe; Haemophilus Vaccines; Hepatitis B Vaccines; Humans; Immunization Programs; Influenza Vaccines; Measles Vaccine; Poliovirus Vaccine, Inactivated; Public Health; Vaccination Coverage; Vaccines, Combined
PubMed: 31990601
DOI: 10.1080/14760584.2020.1717952 -
Vaccine Jun 2023Inactivated polio virus (IPV) vaccinations are a mainstay of immunization schedules in developed countries, while oral polio vaccine (OPV) is administered in developing...
INTRODUCTION
Inactivated polio virus (IPV) vaccinations are a mainstay of immunization schedules in developed countries, while oral polio vaccine (OPV) is administered in developing countries and is the main vaccine in outbreaks. Due to circulating wild poliovirus (WPV1) detection in Israel (2013), oral bivalent polio vaccination (bOPV) was administered to IPV primed children and incorporated into the vaccination regimen.
OBJECTIVES
We aimed to determine the extent and timeframe of fecal and salivary polio vaccine virus (Sabin strains) shedding following bOPV vaccination among IPV primed children.
METHODS
Fecal samples were collected from a convenience sample of infants and toddlers attending 11 Israeli daycare centers. Salivary samples were collected from infants and toddlers following bOPV vaccination.
RESULTS
398 fecal samples were collected from 251 children (ages: 6-32 months), 168 received bOPV vaccination 4-55 days prior to sample collection. Fecal excretion continued among 80 %, 50 %, and 20 %, 2, 3, and 7 weeks following vaccination. There were no significant differences in the rate and duration of positive samples among children immunized with 3 or 4 IPV doses. Boys were 2.3-fold more likely to excrete the virus (p = 0.006). Salivary shedding of Sabin strains occurred in 1/47 (2 %) and 1/49 (2 %) samples 4, and 6 days following vaccination respectively.
CONCLUSIONS
Fecal detection of Sabin strains among IPV-primed children continues for 7 weeks; additional doses of IPV do not augment intestinal immunity; limited salivary shedding occurs for up to a week. This data can enhance understanding of intestinal immunity achieved by different vaccination schedules and guide recommendations for contact precautions of children following bOPV vaccination.
Topics: Male; Humans; Infant; Child, Preschool; Israel; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Poliovirus Vaccine, Inactivated; Vaccination; Immunization Schedule
PubMed: 37268556
DOI: 10.1016/j.vaccine.2023.05.036