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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 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 Feb 2018Infants with history of prematurity (<37 weeks gestation) and low birth weight (LBW, <2500 g) are at high risk of infection due to functional immaturity of normal... (Review)
Review
Immunization of preterm infants with GSK's hexavalent combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine: A review of safety and immunogenicity.
BACKGROUND
Infants with history of prematurity (<37 weeks gestation) and low birth weight (LBW, <2500 g) are at high risk of infection due to functional immaturity of normal physical and immunological defense mechanisms. Despite current recommendations that infants with history of prematurity/LBW should receive routine immunization according to the same schedule and chronological age as full-term infants, immunization is often delayed.
METHODS
Here we summarize 10 clinical studies and 15 years of post-marketing safety surveillance of GSK's hexavalent vaccine (DTPa-HBV-IPV/Hib), a combined diphtheria-tetanus-acellular-pertussis-hepatitis-B-inactivated-poliovirus-Haemophilus influenzae-type-b (Hib) conjugate vaccine, when administered alone, or co-administered with pneumococcal conjugate, rotavirus, and meningococcal vaccines and respiratory syncytial virus IgG to infants with history of prematurity/LBW in clinical trials.
RESULTS
At least 92.5% of infants with history of prematurity/LBW as young as 24 weeks gestation in clinical studies were seropositive to all vaccine antigens after 3-dose primary vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine, with robust immune responses to booster vaccination. Seropositivity rates and antibody concentrations to hepatitis B and Hib appeared lower in infants with history of prematurity/LBW than term infants. Between 13-30% of medically stable infants with history of prematurity developed apnea after vaccination with GSK's hexavalent DTPa-HBV-IPV/Hib vaccine; usually after dose 1. The occurrence of post-immunization cardiorespiratory events appears to be influenced by the severity of any underlying neonatal condition. Most cardiorespiratory events resolve spontaneously or require minimal intervention. GSK's hexavalent DTPa-HBV-IPV/Hib vaccine was well tolerated in co-administration regimens.
CONCLUSION
GSK's hexavalent DTPa-HBV-IPV/Hib vaccine alone or co-administered with other pediatric vaccines has a clinically acceptable safety and immunogenicity profile when used in infants with history of prematurity/LBW for primary and booster vaccination. Additional studies are needed in very premature and very LBW infants. However, currently available data support using GSK's hexavalent DTPa-HBV-IPV/Hib vaccine to immunize infants with history of prematurity/LBW according to chronological age.
Topics: Diphtheria-Tetanus-Pertussis Vaccine; Global Health; Haemophilus Vaccines; Hepatitis B Vaccines; Humans; Immunity, Cellular; Immunogenicity, Vaccine; Infant; Infant, Newborn; Infant, Premature; Morbidity; Mortality; Outcome Assessment, Health Care; Poliovirus Vaccine, Inactivated; Product Surveillance, Postmarketing; Public Health Surveillance; Vaccination; Vaccines, Combined; Vaccines, Conjugate
PubMed: 29336924
DOI: 10.1016/j.vaccine.2018.01.005 -
Journal of Virology Sep 2018The poliovirus eradication initiative has spawned global immunization infrastructure and dramatically decreased the prevalence of the disease, yet the original virus...
The poliovirus eradication initiative has spawned global immunization infrastructure and dramatically decreased the prevalence of the disease, yet the original virus eradication goal has not been met. The suboptimal properties of the existing vaccines are among the major reasons why the program has repeatedly missed eradication deadlines. Oral live poliovirus vaccine (OPV), while affordable and effective, occasionally causes the disease in the primary recipients, and the attenuated viruses rapidly regain virulence and can cause poliomyelitis outbreaks. Inactivated poliovirus vaccine (IPV) is safe but expensive and does not induce the mucosal immunity necessary to interrupt virus transmission. While the need for a better vaccine is widely recognized, current efforts are focused largely on improvements to the OPV or IPV, which are still beset by the fundamental drawbacks of the original products. Here we demonstrate a different design of an antipoliovirus vaccine based on production of virus-like particles (VLPs). The poliovirus capsid protein precursor, together with a protease required for its processing, are expressed from a Newcastle disease virus (NDV) vector, a negative-strand RNA virus with mucosal tropism. In this system, poliovirus VLPs are produced in the cells of vaccine recipients and are presented to their immune systems in the context of active replication of NDV, which serves as a natural adjuvant. Intranasal administration of the vectored vaccine to guinea pigs induced strong neutralizing systemic and mucosal antibody responses. Thus, the vectored poliovirus vaccine combines the affordability and efficiency of a live vaccine with absolute safety, since no full-length poliovirus genome is present at any stage of the vaccine life cycle. A new, safe, and effective vaccine against poliovirus is urgently needed not only to complete the eradication of the virus but also to be used in the future to prevent possible virus reemergence in a postpolio world. Currently, new formulations of the oral vaccine, as well as improvements to the inactivated vaccine, are being explored. In this study, we designed a viral vector with mucosal tropism that expresses poliovirus capsid proteins. Thus, poliovirus VLPs are produced , in the cells of a vaccine recipient, and are presented to the immune system in the context of vector virus replication, stimulating the development of systemic and mucosal immune responses. Such an approach allows the development of an affordable and safe vaccine that does not rely on the full-length poliovirus genome at any stage.
Topics: Animals; Antibodies, Viral; Capsid Proteins; Genetic Vectors; Guinea Pigs; Immunity, Mucosal; Immunoglobulin A; Immunoglobulin G; Newcastle disease virus; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccines; Vaccination; Vaccines, Live, Unattenuated; Vaccines, Virus-Like Particle
PubMed: 29925653
DOI: 10.1128/JVI.00976-18 -
Archivos Argentinos de Pediatria Dec 2016Poliovirus infects 100% of susceptible individuals and causes acute flaccid paralysis in one out of200 infections. Type 1 causes epidemic poliomyelitis; type 2 has been...
Poliovirus infects 100% of susceptible individuals and causes acute flaccid paralysis in one out of200 infections. Type 1 causes epidemic poliomyelitis; type 2 has been eradicated worldwide; and type 3 is close to being eradicated. In this region, the last case of wild poliovirus occurred in Peru in 1991. There are still two endemic countries: Afghanistan and Pakistan, but countries where there is no circulation of the wild poliovirus have also reported imported cases of polio. In May 2012, the World Health Assembly declared the polio eradication a programmatic emergency for global public health and, as a result, developed the Polio Eradication and Endgame Strategic Plan 2013-2018. The Plan has four objectives: 1) Detect and interrupt all poliovirus transmission and maintain surveillance of acute flaccid paralysis in children < 15 years. 2) Strengthen immunization systems and withdraw oral polio vaccine by the first trimester of 2016. Replace the trivalent oral polio vaccine with the bivalent oral vaccine, containing serotypes 1 and 3, and introduce the inactivated polio vaccine in all immunization schedules to maintain immunity against poliovirus type 2. 3) Contain poliovirus and certify interruption of transmission. 4) Plan the exploitation of the fight against polio and its impact on public health. The plan is expected to reach its goals by 2018; all use of the oral polio vaccine will be interrupted thereafter. Change in immunization schedules will require pediatricians to provide advice and guidance to families depending on the varied situations of everyday practice.
Topics: Adolescent; Child; Disease Eradication; Global Health; Humans; Immunization Schedule; Poliomyelitis; Poliovirus Vaccine, Oral; Poliovirus Vaccines; Time Factors
PubMed: 27869415
DOI: 10.5546/aap.2016.eng.557 -
Human Vaccines & Immunotherapeutics Nov 2022An inactivated poliovirus vaccine candidate using Sabin strains (sIPV) grown on the PER.C6® cell line was assessed in infants after demonstrated immunogenicity and... (Randomized Controlled Trial)
Randomized Controlled Trial
Safety and immunogenicity of 3 formulations of a Sabin inactivated poliovirus vaccine produced on the PER.C6® cell line: A phase 2, double-blind, randomized, controlled study in infants vaccinated at 6, 10 and 14 weeks of age.
An inactivated poliovirus vaccine candidate using Sabin strains (sIPV) grown on the PER.C6® cell line was assessed in infants after demonstrated immunogenicity and safety in adults. The study recruited 300 infants who were randomized (1:1:1:1) to receive one of 3 dose levels of sIPV or a conventional IPV based on Salk strains (cIPV). Poliovirus-neutralizing antibodies were measured before the first dose and 28 days after the third dose. Reactogenicity was assessed for 7 days and unsolicited adverse events (AEs) for 28 days after each vaccination. Serious AEs (SAEs) were recorded throughout the study. Solicited AEs were mostly mild to moderate. None of the SAEs reported in the study were judged vaccine related, including one fatal SAE due to aspiration of vomitus that occurred 26 days after the third dose of low-dose sIPV. After 3 sIPV vaccinations and across all dose levels, seroconversion (SC) rates were at least 92% against Sabin poliovirus types and at least 80% against Salk types, with a dose-response in neutralizing antibody geometric mean titers (GMTs) observed across the 3 sIPV groups. Compared to cIPV, the 3 sIPV groups displayed similar or higher SC rates and GMTs against the 3 Sabin types but showed a lower response against Salk types 1 and 2; this was most visible for Salk type 1. While the PER.C6® cell line-based sIPV showed an acceptable safety profile and immunogenicity in infants, lower seroprotection against type 1 warrants optimization of dose level and additional clinical evaluation.
Topics: Adult; Antibodies, Neutralizing; Antibodies, Viral; Cell Line; Humans; Immunogenicity, Vaccine; Infant; Poliomyelitis; Poliovirus; Poliovirus Vaccine, Inactivated; Poliovirus Vaccine, Oral
PubMed: 35344464
DOI: 10.1080/21645515.2022.2044255 -
Expert Review of Vaccines Jun 2017Managing the polio endgame requires access to sufficient quantities of poliovirus vaccines. After oral poliovirus vaccine (OPV) cessation, outbreaks may occur that... (Review)
Review
Managing the polio endgame requires access to sufficient quantities of poliovirus vaccines. After oral poliovirus vaccine (OPV) cessation, outbreaks may occur that require outbreak response using monovalent OPV (mOPV) and/or inactivated poliovirus vaccine. Areas covered: We review the experience and challenges with managing vaccine supplies in the context of the polio endgame. Building on models that explored polio endgame risks and the potential mOPV needs to stop outbreaks from live poliovirus reintroductions, we conceptually explore the potential demands for finished and bulk mOPV doses from a stockpile in the context of limited shelf-life of finished vaccine and time delays to convert bulk to finished vaccine. Our analysis suggests that the required size of the mOPV stockpile varies by serotype, with the highest expected needs for serotype 1 mOPV. Based on realizations of poliovirus risks after OPV cessation, the stockpile required to eliminate the chance of a stock-out appears considerably larger than the currently planned mOPV stockpiles. Expert commentary: The total required stockpile size depends on the acceptable probability of a stock-out, and increases with longer times to finish bulk doses and shorter shelf-lives of finished doses. Successful polio endgame management will require careful attention to poliovirus vaccine supplies.
Topics: Disease Eradication; Humans; Poliomyelitis; Poliovirus Vaccines; Vaccination
PubMed: 28437234
DOI: 10.1080/14760584.2017.1322514 -
Emerging Infectious Diseases Nov 2019Patients with immunodeficiency-associated vaccine-derived poliovirus (iVDPV) are potential poliovirus reservoirs in the posteradication era that might reintroduce...
Patients with immunodeficiency-associated vaccine-derived poliovirus (iVDPV) are potential poliovirus reservoirs in the posteradication era that might reintroduce polioviruses into the community. We update the iVDPV registry in Iran by reporting 9 new patients. In addition to national acute flaccid paralysis surveillance, cases were identified by screening nonparalyzed primary immunodeficiency (PID) patients. Overall, 23 iVDPV patients have been identified since 1995. Seven patients (30%) never had paralysis. Poliovirus screening accelerated the iVDPV detection rate in Iran after 2014.The iVDPV infection rate among nonparalyzed patients with adaptive PID was 3.1% (7/224), several folds higher than previous estimates. Severe combined immunodeficiency patients had the highest risk for asymptomatic infection (28.6%) compared with other PIDs. iVDPV2 emergence has decreased after the switch from trivalent to bivalent oral poliovirus vaccine in 2016. However, emergence of iVDPV1 and iVDPV3 continued. Poliovirus screening in PID patients is an essential step in the endgame of polio eradication.
Topics: Adolescent; Adult; Asymptomatic Diseases; Child; Child, Preschool; Female; Humans; Infant; Iran; Male; Mass Screening; Outcome Assessment, Health Care; Poliomyelitis; Poliovirus; Poliovirus Vaccines; Primary Immunodeficiency Diseases; Public Health Surveillance; Registries; Symptom Assessment; Vaccination; Young Adult
PubMed: 31625840
DOI: 10.3201/eid2511.190540 -
Vaccine Apr 2023Following the global declaration of indigenous wild poliovirus type 2 eradication in 2015, the world switched to oral polio vaccine (OPV) that removed the type 2...
Global oral poliovirus vaccine stockpile management as an essential preparedness and response mechanism for type 2 poliovirus outbreaks following global oral poliovirus vaccine type 2 withdrawal.
Following the global declaration of indigenous wild poliovirus type 2 eradication in 2015, the world switched to oral polio vaccine (OPV) that removed the type 2 component. This 'switch' included the widespread introduction of inactivated poliovirus vaccine and the creation of a stockpile of monovalent type 2 OPV (mOPV2) to respond to potential polio virus Type 2 (PV2) outbreaks and events. With subsequent detection of outbreaks of circulating vaccine-derived poliovirus type 2 (cVDPV2), it was necessary to use this stockpile for outbreak response. Not only were more outbreaks detected than anticipated in the first few years after the switch, but the number of supplemental immunization activities (SIAs) used to stop transmission was often high, and in many cases did not stop wider transmission. Use of mOPV type 2 led in some locations to the emergence of new outbreaks that required further use of the vaccine from the stockpile. In the following years, stockpile management became a critical element of the cVDPV2 outbreak response strategy and continued to evolve to include trivalent OPV and genetically stabilized 'novel OPV type 2' vaccines in the stockpile. An overview of this process and its evolution is presented to highlight several of these management challenges. The unpredictable vaccine demand, fixed production and procurement timelines, resource requirements, and multiple vaccine types contributes to the complexity of assuring appropriate vaccine availability for this critical programmatic need to stop outbreaks.
Topics: Humans; Poliovirus; Poliovirus Vaccine, Oral; Poliomyelitis; Disease Outbreaks; Poliovirus Vaccine, Inactivated; Global Health
PubMed: 35282924
DOI: 10.1016/j.vaccine.2022.02.058 -
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