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The Lancet. Infectious Diseases Apr 2021Following the global eradication of wild poliovirus, countries using live attenuated oral poliovirus vaccines will transition to exclusive use of inactivated poliovirus...
BACKGROUND
Following the global eradication of wild poliovirus, countries using live attenuated oral poliovirus vaccines will transition to exclusive use of inactivated poliovirus vaccine (IPV) or fractional doses of IPV (f-IPV; a f-IPV dose is one-fifth of a normal IPV dose), but IPV supply and cost constraints will necessitate dose-sparing strategies. We compared immunisation schedules of f-IPV and IPV to inform the choice of optimal post-eradication schedule.
METHODS
This randomised open-label, multicentre, phase 3, non-inferiority trial was done at two centres in Panama and one in the Dominican Republic. Eligible participants were healthy 6-week-old infants with no signs of febrile illness or known allergy to vaccine components. Infants were randomly assigned (1:1:1:1, 1:1:1:2, 2:1:1:1), using computer-generated blocks of four or five until the groups were full, to one of four groups and received: two doses of intradermal f-IPV (administered at 14 and 36 weeks; two f-IPV group); or three doses of intradermal f-IPV (administered at 10, 14, and 36 weeks; three f-IPV group); or two doses of intramuscular IPV (administered at 14 and 36 weeks; two IPV group); or three doses of intramuscular IPV (administered at 10, 14, and 36 weeks; three IPV group). The primary outcome was seroconversion rates based on neutralising antibodies for poliovirus type 1 and type 2 at baseline and at 40 weeks (4 weeks after the second or third vaccinations) in the per-protocol population to allow non-inferiority and eventually superiority comparisons between vaccines and regimens. Three co-primary outcomes concerning poliovirus types 1 and 2 were to determine if seroconversion rates at 40 weeks of age after a two-dose regimen (administered at weeks 14 and 36) of intradermally administered f-IPV were non-inferior to a corresponding two-dose regimen of intramuscular IPV; if seroconversion rates at 40 weeks of age after a two-dose IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose IPV regimen (weeks 10, 14, and 36); and if seroconversion rates after a two-dose f-IPV regimen (weeks 14 and 36) were non-inferior to those after a three-dose f-IPV regimen (weeks 10, 14, and 36). The non-inferiority boundary was set at -10% for the lower bound of the two-sided 95% CI for the seroconversion rate difference.. Safety was assessed as serious adverse events and important medical events. This study is registered on ClinicalTrials.gov, NCT03239496.
FINDINGS
From Oct 23, 2017, to Nov 13, 2018, we enrolled 773 infants (372 [48%] girls) in Panama and the Dominican Republic (two f-IPV group n=217, three f-IPV group n=178, two IPV group n=178, and three IPV group n=200). 686 infants received all scheduled vaccine doses and were included in the per-protocol analysis. We observed non-inferiority for poliovirus type 1 seroconversion rate at 40 weeks for the two f-IPV dose schedule (95·9% [95% CI 92·0-98·2]) versus the two IPV dose schedule (98·7% [95·4-99·8]), and for the three f-IPV dose schedule (98·8% [95·6-99·8]) versus the three IPV dose schedule (100% [97·9-100]). Similarly, poliovirus type 2 seroconversion rate at 40 weeks for the two f-IPV dose schedule (97·9% [94·8-99·4]) versus the two IPV dose schedule (99·4% [96·4-100]), and for the three f-IPV dose schedule (100% [97·7-100]) versus the three IPV dose schedule (100% [97·9-100]) were non-inferior. Seroconversion rate for the two f-IPV regimen was statistically superior 4 weeks after the last vaccine dose in the 14 and 36 week schedule (95·9% [92·0-98·2]) compared with the 10 and 14 week schedule (83·2% [76·5-88·6]; p=0·0062) for poliovirus type 1. Statistical superiority of the 14 and 36 week schedule was also found for poliovirus type 2 (14 and 36 week schedule 97·9% [94·8-99·4] vs 10 and 14 week schedule 83·9% [77·2-89·2]; p=0·0062), and poliovirus type 3 (14 and 36 week schedule 84·5% [78·7-89·3] vs 10 and 14 week schedule 73·3% [65·8-79·9]; p=0·0062). For IPV, a two dose regimen administered at 14 and 36 weeks (99·4% [96·4-100]) was superior a 10 and 14 week schedule (88·9% [83·4-93·1]; p<0·0001) for poliovirus type 2, but not for type 1 (14 and 36 week schedule 98·7% [95·4-99·8] vs 10 and 14 week schedule 95·6% [91·4-98·1]), or type 3 (14 and 36 week schedule 97·4% [93·5-99·3] vs 10 and 14 week schedule 93·9% [89·3-96·9]). There were no related serious adverse events or important medical events reported in any group showing safety was unaffected by administration route or schedule.
INTERPRETATION
Our observations suggest that adequate immunity against poliovirus type 1 and type 2 is provided by two doses of either IPV or f-IPV at 14 and 36 weeks of age, and broad immunity is provided with three doses of f-IPV, enabling substantial savings in cost and supply. These novel clinical data will inform global polio immunisation policy for the post-eradication era.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Antibodies, Viral; Dominican Republic; Female; Humans; Immunization Schedule; Immunogenicity, Vaccine; Infant; Infant, Newborn; Male; Panama; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Seroconversion
PubMed: 33284114
DOI: 10.1016/S1473-3099(20)30555-7 -
Vaccine Aug 2017The European Region, certified polio-free in 2002, remains at risk of wild poliovirus reintroduction and emergence of circulating vaccine-derived polioviruses (cVDPV)... (Review)
Review
BACKGROUND
The European Region, certified polio-free in 2002, remains at risk of wild poliovirus reintroduction and emergence of circulating vaccine-derived polioviruses (cVDPV) until global polio eradication is achieved, as demonstrated by the cVDPV1 outbreak in Ukraine in 2015.
METHODS
We reviewed epidemiologic, clinical and virology data on cVDPV cases, surveillance and immunization coverage data, and reports of outbreak-related surveys, country missions, and expert group meetings.
RESULTS
In Ukraine, 3-dose polio vaccine coverage declined from 91% in 2008 to 15% by mid-2015. In summer, 2015, two unrelated children from Zakarpattya province were paralyzed by a highly divergent cVDPV1. The isolates were 20 and 26 nucleotide divergent from prototype Sabin strain (with 18 identical mutations) consistent with their common origin and ∼2-year evolution. Outbreak response recommendations developed with international partner support included conducting three nationwide supplementary immunization activities (SIAs) with tOPV, strengthening surveillance and implementing communication interventions. SIAs were conducted during October 2015-February 2016 (officially reported coverage, round 1-64.4%, round 2-71.7%, and round 3-80.7%). Substantial challenges to outbreak response included lack of high-level support, resistance to OPV use, low perceived risk of polio, widespread vaccine hesitancy, anti-vaccine media environment, economic crisis and military conflict. Communication activities improved caregiver awareness of polio and confidence in vaccination. Surveillance was enhanced but did not consistently meet applicable performance standards. Post-outbreak assessments concluded that cVDPV1 transmission in Ukraine has likely stopped following the response, but significant gaps in population immunity and surveillance remained.
CONCLUSIONS
Chronic under-vaccination in Ukraine resulted in the accumulation of children susceptible to polioviruses and created favorable conditions for VDPV1 emergence and circulation, leading to the outbreak. Until programmatic gaps in immunization and surveillance are addressed, Ukraine will remain at high-risk for VDPV emergence and circulation, as well as at risk for other vaccine-preventable diseases.
Topics: Adolescent; Child; Disease Eradication; Disease Outbreaks; Female; Humans; Infant; Male; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Poliovirus Vaccines; Ukraine; Vaccination; Vaccination Refusal
PubMed: 28528761
DOI: 10.1016/j.vaccine.2017.04.036 -
Human Vaccines & Immunotherapeutics Dec 2024This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three... (Randomized Controlled Trial)
Randomized Controlled Trial
A phase 3 randomized, open-label study evaluating the immunogenicity and safety of concomitant and staggered administration of a live, pentavalent rotavirus vaccine and an inactivated poliomyelitis vaccine in healthy infants in China.
This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from - 4.3% to - 1.6%, for all poliovirus types, < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.
Topics: Humans; Infant; Antibodies, Neutralizing; Antibodies, Viral; China; Immunogenicity, Vaccine; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Rotavirus Vaccines; Vaccines, Attenuated
PubMed: 38509699
DOI: 10.1080/21645515.2024.2324538 -
The Israel Medical Association Journal... Oct 2016
Topics: Animals; Encephalomyelitis, Acute Disseminated; Guillain-Barre Syndrome; Humans; Poliovirus Vaccine, Oral
PubMed: 28471623
DOI: No ID Found -
Medecine Tropicale Et Sante... Jun 2021In 2019, the Central African Republic identified foci of circulating vaccine-derived poliovirus 2 (PVDV2c). The objective of this work is to describe the vaccination...
OBJECTIVE
In 2019, the Central African Republic identified foci of circulating vaccine-derived poliovirus 2 (PVDV2c). The objective of this work is to describe the vaccination status of children paralyzed by PVDV2c and their contacts and to assess the circulation of this strain in these contacts.
PATIENTS AND METHOD
The study population of this retrospective survey consists of children with acute flaccid paralysis (AFP) and their contacts. We included paralyzed children whose sequencing results showed the presence of PVDV2c.
RESULTS
A total of 21 children paralyzed by PVDVc and 64 contacts were enrolled in the survey. Fourteen out of 21 children who are paralyzed (66%) received at least one dose of bivalent oral polio vaccine (OPV) compared to 36 out of 64 contacts (57%, non-significant difference). Of the vaccinated patients, 7 had received less than three doses. For the injectable polio vaccine (IPV), vaccination coverage for both patients and contacts was 33%.The proportion of children who received both doses of OPV and IPV was 33% among patients and 25% in contacts. Contacts with VDPV2 were vaccinated with OPV and IPV, respectively 55 and 27%. VDPV2 and Sabin 2 were also found in contact stools, 34% and 9% respectively.
CONCLUSION
The absence or inadequacy of IPV vaccination has a serious impact on children by the occurrence of virus derived from the vaccine responsible for life-old paralysis. Protecting children from poliomyelitis requires a combination of a good cold chain, multiple doses and adherence to the vaccine schedule.
Topics: Central African Republic; Child; Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Poliovirus Vaccines; Retrospective Studies
PubMed: 35586583
DOI: 10.48327/mtsibulletin.2021.114 -
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 -
Vaccine Oct 2016Significant progress has been made to increase access to vaccines in Africa since the 1974 launch of the Expanded Programme on Immunization (EPI). Successes include the... (Review)
Review
BACKGROUND
Significant progress has been made to increase access to vaccines in Africa since the 1974 launch of the Expanded Programme on Immunization (EPI). Successes include the introduction of several new vaccines across the continent and likely eradication of polio. We examined the contribution of polio eradication activities (PEI) on new vaccine introduction in the countries of the African Region.
METHODS
We reviewed country specific PEI reports to identify best practices relevant to new vaccine introduction (NVI), and analyzed trends in vaccine coverage during 2010-2015 from immunization estimates provided by WHO/UNICEF.
RESULTS
Of the 47 countries in African Region 35 (74%) have introduced PCV, 27 (57%) have introduced rotavirus, and 14 (30%) have introduced IPV. National introductions for HPV vaccine have been done in 5 countries, while 15 countries have held demonstration and pilot projects. In 2014, the regional coverage for the third dose of PCV (PCV3) and rotavirus vaccines was 50% and 30% respectively. By end of 2015, all countries within the meningitis belt will have introduced MenAfriVac™ vaccine.
CONCLUSIONS
PEI activities had a positive effect in strengthening the process of new vaccine introduction in the African Region. The major contribution was in availing immunization funding and providing trained and experienced technical staff to introduce vaccines. More investment is needed to advocate and sustain funding levels to maintain the momentum gained in introducing new vaccines in the region.
Topics: Africa; Disease Eradication; Global Health; Humans; Immunization Programs; Papillomavirus Vaccines; Poliomyelitis; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Rotavirus Vaccines; United Nations; Vaccination Coverage; World Health Organization
PubMed: 27396517
DOI: 10.1016/j.vaccine.2016.05.063 -
Risk Analysis : An Official Publication... Feb 2021COVID-19 led to a recent high-profile proposal to reintroduce oral poliovirus vaccine (OPV) in the United States (U.S.), initially in clinical trials, but potentially... (Review)
Review
COVID-19 led to a recent high-profile proposal to reintroduce oral poliovirus vaccine (OPV) in the United States (U.S.), initially in clinical trials, but potentially for widespread and repeated use. We explore logistical challenges related to U.S. OPV administration in 2020, review the literature related to nonspecific effects of OPV to induce innate immunity, and model the health and economic implications of the proposal. The costs of reintroducing a single OPV dose to 331 million Americans would exceed $4.4 billion. Giving a dose of bivalent OPV to the entire U.S. population would lead to an expected 40 identifiable cases of vaccine-associated paralytic polio, with young Americans at the highest risk. Reintroducing any OPV use in the U.S. poses a risk of restarting transmission of OPV-related viruses and could lead to new infections in immunocompromised individuals with B-cell related primary immunodeficiencies that could lead to later cases of paralysis. Due to the lack of a currently licensed OPV in the U.S., the decision to administer OPV to Americans for nonspecific immunological effects would require purchasing limited global OPV supplies that could impact polio eradication efforts. Health economic modeling suggests no role for reintroducing OPV into the U.S. with respect to responding to COVID-19. Countries that currently use OPV experience fundamentally different risks, costs, and benefits than the U.S. Successful global polio eradication will depend on sufficient OPV supplies, achieving and maintaining high OPV coverage in OPV-using countries, and effective global OPV cessation and containment in all countries, including the U.S.
Topics: COVID-19; COVID-19 Vaccines; Clinical Trials as Topic; Disease Eradication; Disease Outbreaks; Economics, Medical; Female; Global Health; Health Care Costs; Humans; Male; Poliomyelitis; Poliovirus Vaccine, Oral; Risk Management; United States; Vaccination
PubMed: 33084153
DOI: 10.1111/risa.13614 -
Vaccine Apr 2023Concurrent outbreaks of circulating vaccine-derived poliovirus serotypes 1 and 2 (cVDPV1, cVDPV2) were confirmed in the Republic of the Philippines in September 2019 and...
Concurrent outbreaks of circulating vaccine-derived poliovirus serotypes 1 and 2 (cVDPV1, cVDPV2) were confirmed in the Republic of the Philippines in September 2019 and were subsequently confirmed in Malaysia by early 2020. There is continuous population subgroup movement in specific geographies between the two countries. Outbreak response efforts focused on sequential supplemental immunization activities with monovalent Sabin strain oral poliovirus vaccine type 2 (mOPV2) and bivalent oral poliovirus vaccines (bOPV, containing Sabin strain types 1 and 3) as well as activities to enhance poliovirus surveillance sensitivity to detect virus circulation. A total of six cVDPV1 cases, 13 cVDPV2 cases, and one immunodeficiency-associated vaccine-derived poliovirus type 2 case were detected, and there were 35 cVDPV1 and 31 cVDPV2 isolates from environmental surveillance sewage collection sites. No further cVDPV1 or cVDPV2 have been detected in either country since March 2020. Response efforts in both countries encountered challenges, particularly those caused by the global COVID-19 pandemic. Important lessons were identified and could be useful for other countries that experience outbreaks of concurrent cVDPV serotypes.
Topics: Humans; Poliovirus; Poliomyelitis; Malaysia; Philippines; Pandemics; COVID-19; Poliovirus Vaccine, Oral; Disease Outbreaks
PubMed: 35337673
DOI: 10.1016/j.vaccine.2022.02.022 -
Human Vaccines & Immunotherapeutics Jun 2021Human immunodeficiency virus (HIV)-exposed infants may be at increased risk of vaccine-preventable disease. This study was conducted as a post-licensure commitment in... (Randomized Controlled Trial)
Randomized Controlled Trial
Human immunodeficiency virus (HIV)-exposed infants may be at increased risk of vaccine-preventable disease. This study was conducted as a post-licensure commitment in this population to evaluate the primary series, antibody persistence, and booster response to a licensed fully liquid hexavalent vaccine containing diphtheria (D), tetanus (T), acellular pertussis (aP), inactivated poliovirus (IPV), hepatitis B (HB), and type b antigens (PRP~T). This was a Phase III, open-label, randomized study conducted at a single center in the Republic of South Africa. The DTaP-IPV-HB-PRP~T vaccine was administered to HIV-exposed infected (Group A: N = 14) and HIV-exposed uninfected (Group B: N = 50) infants as a 6, 10, 14 week primary series with a toddler booster at 15-18 months of age. Immunogenicity of each antigen was measured using validated assays and vaccine reactogenicity was recorded using diary cards. The low number of HIV-exposed infected participants, due to widespread pre- and peri-natal retroviral treatment, meant that between-group comparisons should be treated with caution. In each group, primary series and booster immune seroprotection rates were strong, and pre-booster antibody persistence was good, although anti-HBs ≥10 mIU/mL in Group A was 78.6% post-primary series, 58.3% pre-booster, and 75.0% post-booster. There were no safety concerns. In conclusion, primary series and booster vaccination of the DTaP-IPV-HB-PRP~T vaccine were immunogenic and safe in HIV-exposed infected and uninfected infants. These results were comparable to historical data in healthy infants and toddlers.
Topics: Antibodies, Bacterial; Antibodies, Viral; Child; Diphtheria-Tetanus-Pertussis Vaccine; HIV Infections; Haemophilus Vaccines; Hepatitis B Vaccines; Humans; Immunization Schedule; Immunization, Secondary; Infant; Poliovirus Vaccine, Inactivated; South Africa; Vaccines, Combined
PubMed: 33326316
DOI: 10.1080/21645515.2020.1839289