Cost-Minimization and Budget Impact Analysis of a Hexavalent Vaccine (Hexaxim®) in the Colombian Expanded Program on Immunization.

OBJECTIVES: To evaluate cost implications of a hexavalent vaccine (diphtheria, tetanus, and acellular pertussis [DTaP]-inactivated polio vaccine [IPV]-hepatitis B [HB]-Haemophilus influenzae type B [Hib] polysaccharide conjugated to T protein [PRP∼T]) as an alternative to DT-whole-cell pertussis (wP)-HB//Hib, DTwP, IPV, and oral polio vaccines in the Expanded Program on Immunization schedule in Colombia. METHODS: Primary vaccination (DTaP-IPV-HB-PRP∼T or DTwP-HB-Hib + IPV [2, 4, 6 months]) and booster (DTaP-IPV-HB-PRP∼T or DTwP + oral polio vaccine [18 months]) (scenario 1) and primary vaccination only (DTaP-IPV-HB-PRP∼T or DTwP-HB-Hib + IPV) (scenario 2) were evaluated. An estimated cost-minimization analysis was based on a micro costing technique for vaccination-associated activities. Adverse event (AE)-associated costs, out-of-pocket costs, and productivity losses for caregivers were included. A budget impact (12-month temporal horizon) was estimated according to the distribution of full-term and premature infants. A 5% annual discount rate was used. A 2-way univariate (tornado) analysis evaluated which variables had the greatest impact on the overall cost. RESULTS: DTaP-IPV-HB-PRP∼T resulted in a cost increase of 29.38% (scenario 1) and 22.19% (scenario 2) for full-term infants and a decrease of 0.99% (scenario 1) and 18.88% (scenario 2) for premature infants, probably because of the higher incidence of wP-related AEs and associated costs in premature infants. With a 100% replacement rate, the budget impact for full-term infants and full-term plus premature infants was 23.73% and 21.80% (scenario 1), respectively, and 13.02% and 11.14% (scenario 2), respectively, of the national immunization program budget. The variables with most impact were the hexavalent vaccine price and costs associated with the pentavalent safety profile. CONCLUSIONS: Incorporation of the hexavalent vaccine in the Expanded Program on Immunization schedule would lead to an increase in spending largely mitigated by reduced AE incidence and reduced logistic and social costs.

Health and Economic Outcomes Associated with Polio Vaccine Policy Options: 2019-2029.

The polio endgame remains complicated, with many questions about future polio vaccines and national immunization policies. We simulated possible future poliovirus vaccine routine immunization policies for countries stratified by World Bank Income Levels and estimated the expected costs and cases using an updated integrated dynamic poliovirus transmission, stochastic risk, and economic model. We consider two reference cases scenarios: one that achieves the eradication of all wild polioviruses (WPVs) by 2023 and one in which serotype 1 WPV (WPV1) transmission continues. The results show that the addition of inactivated poliovirus vaccine (IPV) to routine immunization in all countries substantially increased the expected costs of the polio endgame, without substantially increasing its expected health or economic benefits. Adding a second dose of IPV to the routine immunization schedules of countries that currently include a single IPV dose further increases costs and does not appear economically justified in the reference case that does not stop WPV transmission. For the reference case that includes all WPV eradication, adding a second IPV dose at the time of successful oral poliovirus vaccine (OPV) cessation represents a cost-effective option. The risks and costs of needing to restart OPV use change the economics of the polio endgame, although the time horizon used for modeling impacts the overall economic results. National health leaders will want to consider the expected health and economic net benefits of their national polio vaccine strategies recognizing that preferred strategies may differ.

An Updated Economic Analysis of the Global Polio Eradication Initiative.

Despite a strong global commitment, polio eradication efforts continue now more than 30 years after the 1988 World Health Assembly resolution that established the Global Polio Eradication Initiative (GPEI), and 20 years after the original target of the year 2000. Prior health economic analyses estimated incremental net benefits of the GPEI of 40-50 billion in 2008 U.S. dollars (US$2008, equivalent to 48-59 billion US$2019), assuming the achievement of polio eradication by 2012. Given the delays in achieving polio eradication and increased costs, we performed an updated economic analysis of the GPEI using an updated integrated global model, and considering the GPEI trajectory as of the beginning of 2020. Applying similar methods and assuming eradication achievement in 2023, we estimate incremental net benefits of the GPEI of 28 billion US$2019, which falls below the prior estimate. Delays in achieving polio eradication combined with the widescale introduction of relatively expensive inactivated poliovirus vaccine significantly increased the costs of the GPEI and make it less cost-effective, although the GPEI continues to yield expected incremental net benefits at the global level when considered over the time horizon of 1988-2029. The overall health and financial benefits of the GPEI will depend on whether and when the GPEI can achieve its goals, when eradication occurs, the valuation method applied, and the path dependence of the actions taken. Reduced expected incremental net benefits of the GPEI and the substantial economic impacts of the COVID-19 pandemic pose large financial risks for the GPEI.

Potential Future Use, Costs, and Value of Poliovirus Vaccines.

Countries face different poliovirus risks, which imply different benefits associated with continued and future use of oral poliovirus vaccine (OPV) and/or inactivated poliovirus vaccine (IPV). With the Global Polio Eradication Initiative (GPEI) continuing to extend its timeline for ending the transmission of all wild polioviruses and to introduce new poliovirus vaccines, the polio vaccine supply chain continues to expand in complexity. The increased complexity leads to significant uncertainty about supply and costs. Notably, the strategy of phased OPV cessation of all three serotypes to stop all future incidence of poliomyelitis depends on successfully stopping the transmission of all wild polioviruses. Countries also face challenges associated with responding to any outbreaks that occur after OPV cessation, because stopping transmission of such outbreaks requires reintroducing the use of the stopped OPV in most countries. National immunization program leaders will likely consider differences in their risks and willingness-to-pay for risk reduction as they evaluate their investments in current and future polio vaccination. Information about the costs and benefits of future poliovirus vaccines, and discussion of the complex situation that currently exists, should prove useful to national, regional, and global decisionmakers and support health economic modeling. Delays in achieving polio eradication combined with increasing costs of poliovirus vaccines continue to increase financial risks for the GPEI.

Valuing the cost of improving Chilean primary vaccination: a cost minimization analysis of a hexavalent vaccine.

BACKGROUND: The phased withdrawal of oral polio vaccine (OPV) and the introduction of inactivated poliovirus vaccine (IPV) is central to the polio 'end-game' strategy. METHODS: We analyzed the cost implications in Chile of a switch from the vaccination scheme consisting of a pentavalent vaccine with whole-cell pertussis component (wP) plus IPV/OPV vaccines to a scheme with a hexavalent vaccine with acellular pertussis component (aP) and IPV (Hexaxim®) from a societal perspective. Cost data were collected from a variety of sources including national estimates and previous vaccine studies. All costs were expressed in 2017 prices (US$ 1.00 = $Ch 666.26). RESULTS: The overall costs associated with the vaccination scheme (4 doses of pentavalent vaccine plus 1 dose IPV and 3 doses OPV) from a societal perspective was estimated to be US$ 12.70 million, of which US$ 8.84 million were associated with the management of adverse events related to wP. In comparison, the cost associated with the 4-dose scheme with a hexavalent vaccine (based upon the PAHO reference price) was US$ 19.76 million. The cost of switching to the hexavalent vaccine would be an additional US$ 6.45 million. Overall, depending on the scenario, the costs of switching to the hexavalent scheme would range from an additional US$ 2.62 million to US$ 6.45 million compared with the current vaccination scheme. CONCLUSIONS: The switch to the hexavalent vaccine schedule in Chile would lead to additional acquisition costs, which would be partially offset by improved logistics, and a reduction in adverse events associated with the current vaccines.

The impact of vaccine procurement methods on public health in selected European countries.

Introduction: 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.Areas covered: 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.Expert opinion: 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.

Projection of Costs of Polio Eradication Compared to Permanent Control.

Despite increased efforts and spending toward polio eradication, it has yet to be eliminated worldwide. We aimed to project economic costs of polio eradication compared to permanent control. We used historical Financial Resource Requirements from the Global Polio Eradication Initiative, as well as vaccination and population data from publicly available sources, to project costs for routine immunization, immunization campaigns, surveillance and laboratory resources, technical assistance, social mobilization, treatment, and overhead. We found that cumulative spending for a control strategy would exceed that for an eradication strategy in 2032 (range, 2027-2051). Eradication of polio would likely be cost-saving compared to permanent control.

Joint evaluation of marketing authorization files of inactivated polio vaccines in countries of the Eastern Mediterranean Region.

BACKGROUND: In 2012, the World Health Assembly declared ending polio a "programmatic emergency for global public health". In response, the Global Polio Eradication Initiative developed "The Polio Eradication and Endgame Strategic Plan 2013-2018" to address the eradication of all types of poliomyelitis. AIMS: The World Health Organization invited selected countries in the Eastern Mediterranean Region to take part in a joint evaluation of the marketing authorization files of candidate standalone inactivated poliovirus vaccines (IPVs), aimed to facilitate the evaluation process and expedite the timelines for registration. METHODS: This report describes the planning, organization and execution of the joint meeting among 6 countries of Eastern Mediterranean Region. RESULTS: Participants prepared a joint list of questions and concerns which was shared and discussed with the respective manufacturers on the last day of the review. Manufacturer provided answers to the questions. The questions that could not be responded to immediately by the manufacturer remained to be addressed after the meeting directly between the manufacturer and the national regulatory authoritys. A final joint evaluation report was prepared before the end of the meeting by the participating countries. CONCLUSIONS: The report focuses on the benefits of the exercise and highlights its shortcomings as a sole strategy to secure the timely registration of the vaccine in target countries. We discuss additional aspects to be addressed to effectively accelerate registration, and hence access to priority vaccines.

Analysis of the dose-sparing effect of adjuvanted Sabin-inactivated poliovirus vaccine (sIPV).

Sabin-based inactivated poliovirus vaccine(sIPV) is gradually replacing live-attenuated oral polio vaccine(OPV). Sabin-inactivated poliovirus vaccine(sIPV) has played a vital role in reducing economic burden of poliomyelitis and maintaining appropriate antibody levels in the population. However, due to its high cost and limited manufacturing capacity, sIPV cannot reach its full potential for global poliovirus eradication in developing countries. Therefore, to address this situation, we designed this study to evaluate the dose-sparing effects of AS03, CpG oligodeoxynucleotides (CpG-ODN) and polyinosinic:polycytidylic acid (PolyI:C) admixed with sIPV in rats. Our results showed that a combination of 1/4-dose sIPV adjuvanted with AS03 or AS03 with BW006 provides a seroconversion rate similar to that of full-dose sIPV without adjuvant and that, this rate is 5-fold higher than that of 1/4-dose sIPV without adjuvant after the first immunization. The combination of AS03 or AS03 with BW006 as an adjuvant effectively reduced sIPV dose by at least 4-fold and induced both humoral and cellular immune responses. Therefore, our study revealed that the combination of AS03 or AS03 with BW006 is a promising adjuvant for sIPV development.

Exceptional Financial Support for Introduction of Inactivated Polio Vaccine in Middle-Income Countries.

In May 2012, the World Health Assembly declared the completion of poliovirus eradication a programmatic emergency for global public health and called for a comprehensive polio endgame strategy. The Polio Eradication and Endgame Strategic Plan 2013-2018 was developed in response to this call and demands that all countries using Oral Polio Vaccine (OPV) only introduce at least 1 dose of Inactivated Polio Vaccine (IPV) into routine immunization schedules by the end of 2015. In November 2013, the Board of Gavi (the Vaccine Alliance) approved the provision of support for IPV introduction in the 72 Gavi-eligible countries. Following analytical work and stakeholder consultations, the IPV Immunization Systems Management Group (IMG) presented a proposal to provide exceptional financial support for IPV introduction to additional OPV-only using countries not eligible for Gavi support and that would otherwise not be able to mobilize the necessary financial resources within the Polio Eradication and Endgame Strategic Plan timelines. In June 2014, the Polio Oversight Board (POB) agreed to make available a maximum envelope of US $45 million toward supporting countries not eligible for Gavi funding. This article describes the design of the funding mechanism that was developed, its implementation and the lessons learned through this process.

Intradermal Administration of Fractional Doses of Inactivated Poliovirus Vaccine: A Dose-Sparing Option for Polio Immunization.

A fractional dose of inactivated poliovirus vaccine (fIPV) administered by the intradermal route delivers one fifth of the full vaccine dose administered by the intramuscular route and offers a potential dose-sparing strategy to stretch the limited global IPV supply while further improving population immunity. Multiple studies have assessed immunogenicity of intradermal fIPV compared with the full intramuscular dose and demonstrated encouraging results. Novel intradermal devices, including intradermal adapters and disposable-syringe jet injectors, have also been developed and evaluated as alternatives to traditional Bacillus Calmette-Guérin needles and syringes for the administration of fIPV. Initial experience in India, Pakistan, and Sri Lanka suggests that it is operationally feasible to implement fIPV vaccination on a large scale. Given the available scientific data and operational feasibility shown in early-adopter countries, countries are encouraged to consider introducing a fIPV strategy into their routine immunization and supplementary immunization activities.

Public health impact of Infanrix hexa™ (DTPa-HBV-IPV/Hib) reimbursement: A study programme in France. Part 2: Evolution of the acceptability of infants' vaccination against hepatitis B in general and pediatric practices - the PRALINE study.

BACKGROUND: The reimbursement of the hexavalent vaccine (Infanrix hexa™), comprising the DTPa-IPV-Hib components and the hepatitis B recombinant in a single vaccine, was approved in France in March of 2008. The impact of its reimbursement on physicians' decisions to vaccinate infants against hepatitis B was assessed in a study conducted with general practitioners and pediatricians. METHODS: The PRALINE study (NCT01777074) was a national, cross-sectional, repeated study with two measurement periods (T1 and T2) that measured the changes in physicians' acceptance of hepatitis B vaccination of infants before and for the 3 years after the approval of the hexavalent vaccine reimbursement. Two patient registers were created for each measurement period to enroll the first 15 12- to 15-month-old infants and the first 15 24- to 27-month-old children seen by the practitioners. The proportion of eligible children receiving a hepatitis B vaccine for each physician's practice was calculated. Practitioners also answered a vaccination practice questionnaire via telephone interviews. RESULTS: Across the two study periods, 418 general practitioners and 463 pediatricians were recruited and responded to the telephone interview on their vaccination practices. The overall number of children included in the study in both study periods reached almost 20,000. In the general practitioners group, there was a significant increase in the proportion of physicians "practicing hepatitis B vaccination" (i.e., at least 50% of eligible children receiving the initial hepatitis B vaccination) in children 24-27 months old (79% T2 versus 47% T1, P-value [P]<0.001). Similarly, the proportion of pediatricians initiating hepatitis B vaccination increased from 51% (T1) to 94% (T2) (P<0.0001). General practitioners offered hepatitis B vaccination to infants more systematically in the second study period (87% T2 versus 73% T1, P<0.001) and also suggested the use of the hexavalent vaccine to more patients after reimbursement (92% T2 versus 78% T1, P<0.0001). The proportion of pediatricians offering vaccination to every infant was high at T1 (94%) and remained steady (97%) with a high use of the hexavalent vaccine (94% T1 and 96% T2). CONCLUSION: The PRALINE study shows a significant and immediate change in the hepatitis B vaccination practices of general practitioners and pediatricians following hexavalent vaccine reimbursement with a significant increase in hepatitis B vaccine coverage in infants.

Public health impact of Infanrix hexa (DTPa-HBV-IPV/Hib) reimbursement: A study programme in France. Part 1: Evolution of hepatitis B vaccine coverage rates in infants aged less than 27 months, in the general population - the PopCorn study.

BACKGROUND: Reimbursement of the hexavalent vaccine (Infanrix hexa) comprising the DTPa-IPV-Hib components and the hepatitis B valence in a single vaccine was decided in March 2008 in France. The impact of its reimbursement on the hepatitis B vaccine coverage rate was assessed in a study conducted in the general population prior to and after implementation of the reimbursement policy. METHODS: The PopCorn study (NCT01782794) was a national, cross-sectional and repeated study, with four assessment periods over 3 years, from 2009 to 2012, to assess the hepatitis B vaccine coverage in 12- to 15- and 24- to 27-month-old children, vaccinated between 2007 and 2011 and selected by the quota sampling method. Face-to-face interviews were conducted at their homes and vaccination status was collected using their child's health record. Parents were also interviewed on their perceptions and acceptance of hepatitis B vaccination. Three indicators were calculated to assess hepatitis B vaccination coverage: proportions of infants with at least one dose before 6 months of age, with at least two doses before 6 months of age and with a complete schedule at 24 months of age. RESULTS: A total of 4903 children were enrolled in the study. An overall significant increase (P-value [P<0.05]) of the three indicators of interest over the four periods of time was observed for both age groups. The proportion of children receiving hepatitis B vaccination before 6 months increased from 21% at baseline (before vaccine reimbursement) to almost 75% at the last assessment period in 2012. More than 60% of 24- to 27-month-old children received a complete schedule in 2012 compared to 33% at baseline. No significant increases in the proportions of parents "favourable" and "moderately in favour" of hepatitis B vaccination were observed across the four evaluation periods (respectively, 17-22% and 48-50%, P=0.09). CONCLUSION: The rapid increase of hepatitis B vaccination coverage suggests a significant change in hepatitis B vaccination practice related to the hexavalent vaccine's reimbursement. This change was observed in a context of stability regarding parents' perceptions and acceptance of hepatitis B vaccination and of coverage rates for other infant vaccinations.

Estimated costs attributable to events of "out-of-temperature" in the stockpiling of hexavalent vaccines occurring in Italy.

BACKGROUND: Antigens contained in vaccines are inherently unstable biologically; such a characteristic is conferred by their three-dimensional structure. Preserving the ability of the vaccines to protect against disease is necessary to ensure the supervision and monitoring of all steps of the cold chain. DTPa-HBV-IPV/Hib vaccine (Infanrix hexaTM, GSK Vaccines, Belgium) is designed to prevent disease due to diphtheria, tetanus, pertussis (DTP), hepatitis B virus (HBV), poliomyelitis and Haemophilus influenzae type b (Hib); it was first licensed for use in Europe in 2000 and is currently licensed in at least 95 countries. Since October 2013, more than 102 million doses of GSK's DTPa-HBV-IPV/Hib vaccine have been distributed globally, with nearly 15 million doses distributed in Italy. DTPa-HBV-IPV/Hib components are stable up to a temperature of 25°C for 72 hours. Lacking of officially approved stability data may generate some concern in case of cold chain accidents. METHODS: An analysis based on collected data was carried out to estimate potential costs attributable to events of "out-of-temperature" in the stockpiling of hexavalent vaccines occurring in Italy in 2014. RESULTS: The analysis, based on real data, documented that the loss for the National Health Service (NHS) was in the range of 100,000 - 400,000 euros in one year. However, the amount of money that in principle could have been lost would have ranged between nearly half and one million euros/year. CONCLUSIONS: A substantial loss of money was avoided thanks to the availability of officially approved stability data for GSK's DTPa-HBV-IPV/Hib vaccine.

An economic analysis of poliovirus risk management policy options for 2013-2052.

BACKGROUND: The Global Polio Eradication Initiative plans for coordinated cessation of oral poliovirus vaccine (OPV) after interrupting all wild poliovirus (WPV) transmission, but many questions remain related to long-term poliovirus risk management policies. METHODS: We used an integrated dynamic poliovirus transmission and stochastic risk model to simulate possible futures and estimate the health and economic outcomes of maintaining the 2013 status quo of continued OPV use in most developing countries compared with OPV cessation policies with various assumptions about global inactivated poliovirus vaccine (IPV) adoption. RESULTS: Continued OPV use after global WPV eradication leads to continued high costs and/or high cases. Global OPV cessation comes with a high probability of at least one outbreak, which aggressive outbreak response can successfully control in most instances. A low but non-zero probability exists of uncontrolled outbreaks following a poliovirus reintroduction long after OPV cessation in a population in which IPV-alone cannot prevent poliovirus transmission. We estimate global incremental net benefits during 2013-2052 of approximately $16 billion (US$2013) for OPV cessation with at least one IPV routine immunization dose in all countries until 2024 compared to continued OPV use, although significant uncertainty remains associated with the frequency of exportations between populations and the implementation of long term risk management policies. CONCLUSIONS: Global OPV cessation offers the possibility of large future health and economic benefits compared to continued OPV use. Long-term poliovirus risk management interventions matter (e.g., IPV use duration, outbreak response, containment, continued surveillance, stockpile size and contents, vaccine production site requirements, potential antiviral drugs, and potential safer vaccines) and require careful consideration. Risk management activities can help to ensure a low risk of uncontrolled outbreaks and preserve or further increase the positive net benefits of OPV cessation. Important uncertainties will require more research, including characterizing immunodeficient long-term poliovirus excretor risks, containment risks, and the kinetics of outbreaks and response in an unprecedented world without widespread live poliovirus exposure.

sIPV process development for costs reduction.

Polio is expected to be eradicated within only a few years from now. Upon polio eradication, the use of oral polio vaccines, which can cause circulating and virulent vaccine derived polio viruses, will be stopped. From this moment onwards, inactivated polio vaccines (IPV) will be used for worldwide vaccination against polio. An increased demand for IPV is thus anticipated. As a result, process development studies regarding the IPV production process, developed in the 1960s, have intensified. Studies on yield optimization aiming at costs reduction as well as the use of alternative polio viruses, which are more biosafe for manufacturing, are actual. Here our strategy to setup a new IPV production process using attenuated Sabin polio virus strains is presented. Moreover, aspects on reduction of the costs of goods and the impact of process optimization on sIPV costs are reviewed.

Polio inactivated vaccine costs into routine childhood immunization in Brazil.

OBJECTIVE To analyze the costs of vaccination regimens for introducing inactivated polio vaccine in routine immunization in Brazil. METHODS A cost analysis was conducted for vaccines in five vaccination regimens, including inactivated polio vaccine, compared with the oral polio vaccine-only regimen. The costs of the vaccines were estimated for routine use and for the "National Immunization Days", during when the oral polio vaccine is administered to children aged less than five years, independent of their vaccine status, and the strategic stock of inactivated polio vaccine. The presented estimated costs are of 2011. RESULTS The annual costs of the oral vaccine-only program (routine and two National Immunization Days) were estimated at US$19,873,170. The incremental costs of inclusion of the inactivated vaccine depended on the number of vaccine doses, presentation of the vaccine (bottles with single dose or ten doses), and number of "National Immunization Days" carried out. The cost of the regimen adopted with two doses of inactivated vaccine followed by three doses of oral vaccine and one "National Immunization Day" was estimated at US$29,653,539. The concomitant replacement of the DTPw/Hib and HepB vaccines with the pentavalent vaccine enabled the introduction of the inactivated polio without increasing the number of injections or number of visits needed to complete the vaccination. CONCLUSIONS The introduction of the inactivated vaccine increased the annual costs of the polio vaccines by 49.2% compared with the oral vaccine-only regimen. This increase represented 1.13% of the expenditure of the National Immunization Program on the purchase of vaccines in 2011.

Alternative delivery of a thermostable inactivated polio vaccine.

In the near future oral polio vaccine (OPV) will be replaced by inactivated polio vaccine (IPV) as part of the eradication program of polio. For that reason, there is a need for substantial amount of safe and more affordable IPV for low-income countries. Bioneedles, which are biodegradable mini-implants, have the potential to deliver vaccines outside the cold-chain and administer them without the use of needles and syringes. In the current study, Bioneedles were filled with IPV, subsequently lyophilized, and antigenic recoveries were determined both directly after IPV-Bioneedle preparation as well as after elevated stability testing. Further, we assessed the immunogenicity of IPV-Bioneedles in rats and the residence time at the site of administration. Trivalent IPV was formulated in Bioneedles with recoveries of 101±10%, 113±18%, and 92±15%, respectively for serotypes 1, 2 and 3. IPV in Bioneedles is more resistant to elevated temperatures than liquid IPV: liquid IPV retained less than half of its antigenicity after 1 day at 45°C and IPV in Bioneedles showed remaining recoveries of 80±10%, 85±4% and 63±4% for the three serotypes. In vivo imaging revealed that IPV administered via Bioneedles as well as subcutaneously injected liquid IPV showed a retention time of 3 days at the site of administration. Finally, an immunogenicity study showed that IPV-filled Bioneedles are able to induce virus-neutralizing antibody titers similar to those obtained by liquid intramuscular injection when administered in a booster regime. The addition of LPS-derivate PagL in IPV-filled Bioneedles did not increase immunogenicity compared to IPV-Bioneedles without adjuvant. The current study demonstrates the pre-clinical proof of concept of IPV-filled Bioneedles as a syringe-free alternative delivery system. Further pre-clinical and clinical studies will be required to assess the feasibility whether IPV-Bioneedles show sufficient safety and efficacy, and may contribute to the efforts to eradicate and prevent polio in the future.

Aluminium hydroxide potentiates a protective Th1 biased immune response against polio virus that allows for dose sparing in mice and rats.

BACKGROUND: The development of new low cost inactivated polio virus based vaccines (IPV) is a high priority and will be essential for the complete eradication of polio. Since the aluminium hydroxide adjuvant is widely used in humans we tested this adjuvant with IPV in two models. Our objective was twofold; to examine the IPV dose sparing effect of aluminium hydroxide and how the adjuvant effect of aluminium hydroxide affected the immunity induced by IPV. METHODS: Mice and rats were immunized with IPV formulated with Aluminium hydroxide and subjected to immunological analyses and serum polio virus neutralization titer determination. RESULTS: Addition of aluminium hydroxide to IPV led to a ten times dose sparing effect compared to IPV alone, measured by virus neutralization titers in serum. Aluminium hydroxide changed the kinetics of the response against IPV leading to a faster and stronger response, which due to IPV induced immune dominance was characterized as a strong Th1-biased cellular/humoral immune response. CONCLUSIONS: The IPV-aluminium hydroxide formulation constitutes a promising vaccine capable of generating strong Th1 immunity against infection with all three serotypes. A phase I/II clinical study was recently initiated.

Intradermal inactivated poliovirus vaccine: a preclinical dose-finding study.

Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost.