-
Vaccine Sep 2023To inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with... (Randomized Controlled Trial)
Randomized Controlled Trial
Poliovirus type 1 systemic humoral and intestinal mucosal immunity induced by monovalent oral poliovirus vaccine, fractional inactivated poliovirus vaccine, and bivalent oral poliovirus vaccine: A randomized controlled trial.
BACKGROUND
To inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with monovalent oral poliovirus vaccine (mOPV1), and 2) mOPV1 versus bivalent OPV (bOPV).
METHODS
We conducted a randomized, controlled, open-label trial in Dhaka, Bangladesh. Healthy infants aged 5 weeks were block randomized to one of four arms: mOPV1 at age 6-10-14 weeks/fIPV at 6 weeks (A); mOPV1 at 6-10-14 weeks/fIPV at 10 weeks (B); mOPV1 at 6-10-14 weeks (C); and bOPV at 6-10-14 weeks (D). Immune response at 10 weeks and cumulative response at 14 weeks was assessed among the modified intention-to-treat population, defined as seroconversion from seronegative (<1:8 titers) to seropositive (≥1:8) or a four-fold titer rise among seropositive participants sustained to age 18 weeks. We examined virus shedding after two doses of mOPV1 with and without fIPV, and after the first mOPV1 or bOPV dose. The trial is registered at ClinicalTrials.gov (NCT03722004).
FINDINGS
During 18 December 2018 - 23 November 2019, 1,192 infants were enrolled (arms A:301; B:295; C:298; D:298). Immune responses at 14 weeks did not differ after two mOPV1 doses alone (94% [95% CI: 91-97%]) versus two mOPV1 doses with fIPV at 6 weeks (96% [93-98%]) or 10 weeks (96% [93-98%]). Participants who received mOPV1 and fIPV at 10 weeks had significantly lower shedding (p < 0·001) one- and two-weeks later compared with mOPV1 alone. Response to one mOPV1 dose was significantly higher than one bOPV dose (79% versus 67%; p < 0·001) and shedding two-weeks later was significantly higher after mOPV1 (76% versus 56%; p < 0·001) indicating improved vaccine replication. Ninety-nine adverse events were reported, 29 serious including two deaths; none were attributed to study vaccines.
INTERPRETATION
Given with the second mOPV1 dose, fIPV improved intestinal immunity but not humoral immunity. One mOPV1 dose induced higher humoral and intestinal immunity than bOPV.
FUNDING
U.S. Centers for Disease Control and Prevention.
Topics: Humans; Infant; Bangladesh; Immunity, Mucosal; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; United States; Poliomyelitis
PubMed: 37652822
DOI: 10.1016/j.vaccine.2023.08.055 -
Vaccine Nov 2018The World Health Organization recommends the development of affordable next-generation inactivated poliovirus vaccines (IPV) using attenuated poliovirus Sabin strains....
BACKGROUND
The World Health Organization recommends the development of affordable next-generation inactivated poliovirus vaccines (IPV) using attenuated poliovirus Sabin strains. Previously, we introduced a novel PER.C6® cell culture platform, which allows for high yield production of an affordable trivalent Sabin IPV vaccine.
METHODS
Immunogenicity and safety of this novel PER.C6®-based Sabin-IPV (sIPV) was assessed in rats and non-human primates (NHPs). NHPs received one of four different dose dilutions vaccine according to current human schedule (three prime-immunizations and one boost immunization). For comparison, NHPs received commercially available reference Salk IPV or sIPV.
RESULTS
Dose-dependent immunogenicity and good tolerability was observed for the PER.C6®-based sIPV formulations in rats and NHPs. In NHPs, the lowest tested dose that induced anti-Sabin virus-neutralizing antibody titers that were non-inferior to commercial sIPV after three immunizations was 5-7.5-25 D-antigen units for type 1, 2 and 3 respectively.
DISCUSSION
PER.C6®-based sIPV induced comparable immunogenicity to commercial Salk IPV and sIPV vaccines in NHPs. Together with the absence of any preclinical safety signals, these data warrant further testing in clinical trials. sIPV produced on the PER.C6® cell platform could be one solution to the need for an affordable and immunogenic IPV to achieve and maintain global polio eradication.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Cell Culture Techniques; Culture Media, Serum-Free; Female; Immunization Schedule; Macaca fascicularis; Poliovirus; Poliovirus Vaccine, Inactivated
PubMed: 30314910
DOI: 10.1016/j.vaccine.2018.09.068 -
MMWR. Morbidity and Mortality Weekly... Aug 2021In 1988, when the Global Polio Eradication Initiative (GPEI) began, polio paralyzed >350,000 children across 125 countries. Today, only one of three wild poliovirus...
In 1988, when the Global Polio Eradication Initiative (GPEI) began, polio paralyzed >350,000 children across 125 countries. Today, only one of three wild poliovirus serotypes, type 1 (WPV1), remains in circulation in only two countries, Afghanistan and Pakistan. This report summarizes progress toward global polio eradication during January 1, 2019-June 30, 2021 and updates previous reports (1,2). In 2020, 140 cases of WPV1 were reported, including 56 in Afghanistan (a 93% increase from 29 cases in 2019) and 84 in Pakistan (a 43% decrease from 147 cases in 2019). As GPEI focuses on the last endemic WPV reservoirs, poliomyelitis outbreaks caused by circulating vaccine-derived poliovirus (cVDPV) have emerged as a result of attenuated oral poliovirus vaccine (OPV) virus regaining neurovirulence after prolonged circulation in underimmunized populations (3). In 2020, 32 countries reported cVDPV outbreaks (four type 1 [cVDPV1], 26 type 2 [cVDPV2] and two with outbreaks of both); 13 of these countries reported new outbreaks. The updated GPEI Polio Eradication Strategy 2022-2026 (4) includes expanded use of the type 2 novel oral poliovirus vaccine (nOPV2) to avoid new emergences of cVDPV2 during outbreak responses (3). The new strategy deploys other tactics, such as increased national accountability, and focused investments for overcoming the remaining barriers to eradication, including program disruptions and setbacks caused by the COVID-19 pandemic.
Topics: Disease Eradication; Disease Outbreaks; Endemic Diseases; Global Health; Humans; Immunization Programs; Poliomyelitis; Poliovirus Vaccines; Population Surveillance
PubMed: 34437527
DOI: 10.15585/mmwr.mm7034a1 -
Frontiers in Immunology 2022Considering that vaccination with the sIPV and DTaP overlap at the ages of 3 and 4 months in China, to reduce the burden of treatment on parents and increase vaccination... (Randomized Controlled Trial)
Randomized Controlled Trial
Immunogenicity and safety of concomitant administration of the chinese inactivated poliovirus vaccine with the diphtheria-tetanus-acellular pertussis (DTaP) vaccine in children: A multicenter, randomized, non-inferiority, controlled trial.
KEY POINT
Considering that vaccination with the sIPV and DTaP overlap at the ages of 3 and 4 months in China, to reduce the burden of treatment on parents and increase vaccination coverage rates, we designed a postmarket clinical study of co-administration.
BACKGROUND
The Sabin-strain-based inactivated poliovirus vaccine (sIPV) and the diphtheria-tetanus-acellular pertussis vaccine (DTaP) have been licensed in China for many years. To conduct a clinical study on the safety and immunogenicity of the sIPV when administered concomitantly with the DTaP.
METHODS
The study population was divided into three groups: group 1 was the sIPV+ DTaP concomitant administration group, group 2 was the sIPV inoculation group, and group 3 was the DTaP inoculation group. Blood samples were collected prevaccination and 30 days postvaccination, and serum antibody levels were detected.
RESULTS
This study showed that the seropositive and seroconversion rates of type 1, 2 and 3 poliovirus in group 1 were higher than those in group 2, with no statistically significant difference after vaccination (P>0.05). Groups 1 and 3 also showed similar responses for all vaccine antigens except anti-FHA (97.65 (94.09-99.36) vs. 100 (97.89-100)). The geometric mean titers (GMTs) for the DTaP and sIPV among the groups were comparable, and the non-inferiority t test result was P<0.001. The number of local adverse events (AEs) reported in group 1 (29.91%) were larger than those in group 2 (12.39%) and group 3 (21.93%), among which the most common was redness. Similarly, the most common systemic AE was fever. All 5 severe AE (SAE) cases were determined by experts to be unrelated to the vaccines during the study.
CONCLUSIONS
The evidence of similar seroconversion and safety with co-administered DTaP and sIPV supports the co-administration supports the introduction of a strategy of simultaneous administration of both vaccines into routine infant immunization, and it could increase vaccination coverage and protect more infants from morbidity and mortality from these related diseases.
CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT04054882?term=NCT04054882&cntry=CN&draw=2&rank=1, identifier NCT04054882.
Topics: Antibodies, Bacterial; Child; Diphtheria; Diphtheria-Tetanus-acellular Pertussis Vaccines; Humans; Infant; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Tetanus; Vaccines, Combined; Whooping Cough
PubMed: 35958596
DOI: 10.3389/fimmu.2022.905634 -
The Journal of Infectious Diseases Jul 2017The Polio Eradication and Endgame Strategic plan outlines the phased removal of oral polio vaccines (OPVs), starting with type 2 poliovirus-containing vaccine and...
The Polio Eradication and Endgame Strategic plan outlines the phased removal of oral polio vaccines (OPVs), starting with type 2 poliovirus-containing vaccine and introduction of inactivated polio vaccine in routine immunization to mitigate against risk of vaccine-associated paralytic polio and circulating vaccine-derived poliovirus. The objective includes strengthening routine immunization as the primary pillar to sustaining high population immunity. After 2 years without reporting any wild poliovirus (July 2014-2016), the region undertook the synchronized switch from trivalent OPV (tOPV) to bivalent OPV (bOPV) as recommended by the Strategic Advisory Group of Experts on Immunization. Consequently the 47 countries of the World Health Organization (WHO) African Region switched from the use of tOPV to bOPV within the stipulated period of April 2016. Planning started early, routine immunization was strengthened, and technical and financial support was provided for vaccine registration, procurement, destruction, logistics, and management across countries by WHO in collaboration with the United Nations Children's Fund (UNICEF) and partners. National commitment and ownership, as well as strong coordination and collaboration between UNICEF and WHO and with partners, ensured success of this major, historic public health undertaking.
Topics: Africa; Disease Eradication; Global Health; Humans; Immunization Programs; Poliomyelitis; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; World Health Organization
PubMed: 28838178
DOI: 10.1093/infdis/jiw616 -
British Journal of Clinical Pharmacology Dec 2021The bivalent oral poliovirus vaccine (bOPV; Sabin types 1 and 3) replaced the trivalent OPV (Sabin types 1, 2 and 3) globally in April 2016. A routine schedule of 1 dose...
AIMS
The bivalent oral poliovirus vaccine (bOPV; Sabin types 1 and 3) replaced the trivalent OPV (Sabin types 1, 2 and 3) globally in April 2016. A routine schedule of 1 dose of inactivated poliovirus vaccine and 3 subsequent doses of bOPV was implemented in Jiangsu simultaneously. The schedule was changed to 2 inactivated poliovirus vaccines + 2 bOPV on 1 September 2019. Although OPV type 2 has been removed, challenges persist because of adverse events following immunization (AEFIs) with bOPV. Therefore, we analysed and evaluated the safety profile of bOPV administered in children based on passive postmarketing AEFI surveillance.
METHODS
We collected all bOPV-related AEFI reports in Jiangsu from the Chinese National AEFI Information System (CNAEFIS) between May 2016 and April 2020. We obtained the administered doses of bOPV from the Jiangsu Provincial Electronic Immunization Registries System. A descriptive analysis was performed.
RESULTS
In total, 2084 bOPV-related AEFIs were retrieved from the CNAEFIS. The overall reporting rate was 24.16 per 100 000 doses. Most AEFIs were nonserious. The most frequently reported symptoms were fever, rash and gastrointestinal disorders. Only 1.34% of AEFIs were serious, which thrombocytopenic purpura accounted for the largest category. Seventeen serious adverse events, including 2 vaccine-associated paralytic poliomyelitis (VAPP) cases, were considered to be related to bOPV vaccination. The rate of VAPP was 0.2 per million doses.
CONCLUSION
AEFI analysis showed that bOPV was well tolerated. The events most frequently reported were nonserious. However, bOPV can still cause VAPP. Attention should be given to risks related to bOPV.
Topics: Child; China; Humans; Immunization Schedule; Infant; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral; Vaccination
PubMed: 34240463
DOI: 10.1111/bcp.14976 -
Vaccine Apr 2023The global withdrawal of trivalent oral poliovirus vaccine (OPV) (tOPV, containing Sabin poliovirus strains serotypes 1, 2 and 3) from routine immunization, and the...
BACKGROUND
The global withdrawal of trivalent oral poliovirus vaccine (OPV) (tOPV, containing Sabin poliovirus strains serotypes 1, 2 and 3) from routine immunization, and the introduction of bivalent OPV (bOPV, containing Sabin poliovirus strains serotypes 1 and 3) and trivalent inactivated poliovirus vaccine (IPV) into routine immunization was expected to improve population serologic and mucosal immunity to types 1 and 3 poliovirus, while population mucosal immunity to type 2 poliovirus would decline. However, over the period since tOPV withdrawal, the implementation of preventive bOPV supplementary immunization activities (SIAs) has decreased, while outbreaks of type 2 circulating vaccine derived poliovirus (cVDPV2) have required targeted use of monovalent type 2 OPV (mOPV2).
METHODS
We develop a dynamic model of OPV-induced immunity to estimate serotype-specific, district-level immunity for countries in priority regions and characterize changes in immunity since 2016. We account for the changes in routine immunization schedules and varying implementation of preventive and outbreak response SIAs, assuming homogenous coverages of 50% and 80% for SIAs.
RESULTS
In areas with strong routine immunization, the switch from tOPV to bOPV has likely resulted in gains in population immunity to types 1 and 3 poliovirus. However, we estimate that improved immunogenicity of new schedules has not compensated for declines in preventive SIAs in areas with weak routine immunization. For type 2 poliovirus, without tOPV in routine immunization or SIAs, mucosal immunity has declined nearly everywhere, while use of mOPV2 has created highly heterogeneous population immunity for which it is important to take into account when responding to cVDPV2 outbreaks.
CONCLUSIONS
The withdrawal of tOPV and declining allocations of resources for preventive bOPV SIAs have resulted in reduced immunity in vulnerable areas to types 1 and 3 poliovirus and generally reduced immunity to type 2 poliovirus in the regions studied, assuming homogeneous coverages of 50% and 80% for SIAs. The very low mucosal immunity to type 2 poliovirus generates substantially greater risk for further spread of cVDPV2 outbreaks. Emerging gaps in immunity to all serotypes will require judicious targeting of limited resources to the most vulnerable populations by the Global Polio Eradication Initiative (GPEI).
Topics: Humans; Poliovirus; Poliovirus Vaccine, Oral; Poliomyelitis; Serogroup; Vaccination; Poliovirus Vaccine, Inactivated
PubMed: 35339308
DOI: 10.1016/j.vaccine.2022.03.013 -
Lancet (London, England) Jun 2019Intradermal administration of fractional inactivated poliovirus vaccine (fIPV) is a dose-sparing alternative to the intramuscular full dose. We aimed to compare the... (Comparative Study)
Comparative Study Randomized Controlled Trial
Immunogenicity of full and fractional dose of inactivated poliovirus vaccine for use in routine immunisation and outbreak response: an open-label, randomised controlled trial.
BACKGROUND
Intradermal administration of fractional inactivated poliovirus vaccine (fIPV) is a dose-sparing alternative to the intramuscular full dose. We aimed to compare the immunogenicity of two fIPV doses versus one IPV dose for routine immunisation, and also assessed the immunogenicity of an fIPV booster dose for an outbreak response.
METHODS
We did an open-label, randomised, controlled, inequality, non-inferiority trial in two clinics in Dhaka, Bangladesh. Healthy infants were randomly assigned at 6 weeks to one of four groups: group A received IPV at age 14 weeks and IPV booster at age 22 weeks; group B received IPV at age 14 weeks and fIPV booster at age 22 weeks; group C received IPV at age 6 weeks and fIPV booster at age 22 weeks; and group D received fIPV at 6 weeks and 14 weeks and fIPV booster at age 22 weeks. IPV was administered by needle-syringe as an intramuscular full dose (0·5 mL), and fIPV was administered intradermally (0·1 mL of the IPV formulation was administered using the 0·1 mL HelmJect auto-disable syringe with a Helms intradermal adapter). Both IPV and fIPV were administered on the outer, upper right thigh of infants. The primary outcome was vaccine response to poliovirus types 1, 2, and 3 at age 22 weeks (routine immunisation) and age 26 weeks (outbreak response). Vaccine response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) or four-fold increase in reciprocal antibody titres adjusted for maternal antibody decay and was assessed in the modified intention-to-treat population (infants who received polio vaccines per group assignment and polio antibody titre results to serotypes 1, 2, and 3 at 6, 22, 23, and 26 weeks of age). The non-inferiority margin was 12·5%. This trial is registered with ClinicalTrials.gov, number NCT02847026.
FINDINGS
Between Sept 1, 2016 and May 2, 2017, 1076 participants were randomly assigned and included in the modified intention-to-treat analysis: 271 in Group A, 267 in group B, 268 in group C, and 270 in group D. Vaccine response at 22 weeks to two doses of fIPV (group D) was significantly higher (p<0·0001) than to one dose of IPV (groups A and B) for all three poliovirus serotypes: the type 1 response comprised 212 (79% [95% CI 73-83]) versus 305 (57% [53-61]) participants, the type 2 response comprised 173 (64% [58-70]) versus 249 (46% [42-51]) participants, and the type 3 response comprised 196 (73% [67-78]) versus 196 (36% [33-41]) participants. At 26 weeks, the fIPV booster was non-inferior to IPV (group B vs group A) for serotype 1 (-1·12% [90% CI -2·18 to -0·06]), serotype 2 (0·40%, [-2·22 to 1·42]), and serotype 3 (1·51% [-3·23 to -0·21]). Of 129 adverse events, 21 were classified as serious including one death; none were attributed to IPV or fIPV.
INTERPRETATION
fIPV appears to be an effective dose-sparing strategy for routine immunisation and outbreak responses.
FUNDING
US Centers for Disease Control and Prevention.
Topics: Antibodies, Viral; Bangladesh; Disease Outbreaks; Female; Humans; Immunization, Secondary; Infant; Injections, Intramuscular; Male; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated
PubMed: 31104832
DOI: 10.1016/S0140-6736(19)30503-3 -
Future Microbiology Oct 2019Although global polio eradication is within reach, sustained eradication of all polioviruses requires cessation of oral poliovirus vaccine use to mitigate against...
Although global polio eradication is within reach, sustained eradication of all polioviruses requires cessation of oral poliovirus vaccine use to mitigate against vaccine-derived poliovirus circulation and vaccine-associated paralytic poliomyelitis. The first step in this direction was the WHO-recommended global withdrawal of live attenuated type 2 Sabin poliovirus from routine immunisation in May 2016, with future use restricted to outbreak response, and handling controlled by strict containment provisions (GAPIII). This creates unique challenges for development and testing of novel type 2 poliovirus vaccines. We describe the creation of a novel purpose-built containment facility, Poliopolis, to study new monovalent OPV2 vaccine candidates in healthy adult volunteers, which may be a model for future endeavors in vaccine development for emergency use.
Topics: Adult; Containment of Biohazards; Disease Eradication; Disease Outbreaks; Feces; Global Health; Healthy Volunteers; Housing; Humans; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Oral; Quarantine; Vaccination; Vaccines, Attenuated; Virus Shedding; World Health Organization
PubMed: 31482728
DOI: 10.2217/fmb-2019-0196 -
DTaP-IPV-HepB-Hib Vaccine (Hexyon): An Updated Review of its Use in Primary and Booster Vaccination.Paediatric Drugs Oct 2019Hexyon is a fully-liquid, ready-to-use, hexavalent vaccine approved in the EU since 2013 for primary and booster vaccination in infants and toddlers from age 6 weeks... (Review)
Review
Hexyon is a fully-liquid, ready-to-use, hexavalent vaccine approved in the EU since 2013 for primary and booster vaccination in infants and toddlers from age 6 weeks against diphtheria, tetanus, pertussis, hepatitis B (HB), poliomyelitis, and invasive diseases caused by Haemophilus influenzae type b (Hib). While the source of HB antigen in Hexyon is different from other vaccines, the rest of its valences have been extensively used in other approved vaccines. Hexyon is highly immunogenic for all its component toxoids/antigens when used as primary and booster vaccine in infants and toddlers, irrespective of vaccination schedule. It provides durable protection against hepatitis B. Hexyon can be used for a mixed primary series of hexavalent-pentavalent-hexavalent vaccines or as a booster in infants primed with Infanrix hexa™ or pentavalent (whole-cell or acellular pertussis) vaccines. Coadministration of Hexyon with other common childhood vaccines did not affect immune response to any vaccines. Hexyon has a good reactogenicity/safety profile. The immunogenicity and safety profile of Hexyon was similar to that of several approved vaccines, including Infanrix hexa™. However, Hexyon offers the convenience of full-liquid, ready-to-use formulation, which may minimize vaccination errors and preparation time. Thus, Hexyon is a convenient, useful option for vaccination against childhood diseases caused by six major pathogens.
Topics: Diphtheria-Tetanus-Pertussis Vaccine; Female; Haemophilus Vaccines; Hepatitis B Vaccines; Humans; Male; Poliovirus Vaccine, Inactivated; Vaccination; Vaccines, Combined
PubMed: 31444785
DOI: 10.1007/s40272-019-00353-7