World wide experience with inactivated poliovirus vaccine

As part of the global poliovirus eradication strategy, oral poliovirus vaccine (OPV) has successfully contributed to reduce polio incidence rates globally. However, because of the OPV-related risks of vaccine associated paralytic poliomyelitis (VAPP) and vaccine-derived polioviruses (VDPVs) OPV cessation is required in order to achieve complete eradication of polio. Inactivated poliovirus vaccine (IPV) is a viable option for incorporation into existing vaccination schedules so as to avoid these risks. Furthermore, the continuation of vaccination with IPV will protect populations in case of re-emergence of wild-type poliovirus from remote locations, laboratory samples, or through bioterrorism. The ability of IPV to prevent poliovirus outbreaks and provide herd protection has been demonstrated in several circumstances and in various settings. This paper reviews clinical experiences with IPV administration and outcomes in various countries in Europe, the Americas, Africa and Asia.     

End phase challenges of poliomyelitis eradication programme realization

The progress of poliomyelitis eradication programme realization, the implementation schedule and strategies for the future, are summarised based on publications of the World Health Organisation. During the following two years wild poliovirus strains should be globally eradicated. This means that potentially in 2010 the global eradication of wild polioviruses will be certified. To eradicate poliomyelitis, cessation of the oral polio vaccine (OPV) is necessary, since the vaccine strains produce cases of vaccine-associated paralytic poliomyelitis (VAPP) and cases of poliomyelitis caused by circulating vaccine-derived poliovirus (cVDPV). However, the WHO plan to stop immunization with OPV and the immunization with inactivated polio vaccine (IPV) shortly after, is alarming in the present situation. The article describes the measures undertaken to prevent or minimise the risk of reintroduction of wild poliovirus strains, which is potentially associated with WHO plan of action.     

The global introduction of inactivated polio vaccine can circumvent the oral polio vaccine paradox

This literature review identifies the factors that influence the decision to introduce inactivated polio vaccine (IPV) in developing countries as opposed to the policy of vaccine cessation. Attenuated viruses in the oral polio vaccine (OPV) can replicate, revert to neurovirulence and become transmissible circulating vaccine-derived polioviruses (cVDPVs), preventing use of the vaccine in the post-eradication era. This literature review identifies (1) risks of complete cessation of vaccination, (2) barriers and (3) solutions for the introduction of IPV in developing countries. The reviewed literature favours to circumvent the so-called “OPV paradox” by global introduction of IPV.     

Poliomyelitis prevention in the United States. Updated recommendations of the Advisory Committee on Immunization Practices (ACIP).

These recommendations of the Advisory Committee on Immunization Practices (ACIP) for poliomyelitis prevention replace those issued in 1997. As of January 1, 2000, ACIP recommends exclusive use of inactivated poliovirus vaccine (IPV) for routine childhood polio vaccination in the United States. All children should receive four doses of IPV at ages 2, 4, and 6-18 months and 4-6 years. Oral poliovirus vaccine (OPV) should be used only in certain circumstances, which are detailed in these recommendations. Since 1979, the only indigenous cases of polio reported in the United States have been associated with the use of the live OPV. Until recently, the benefits of OPV use (i.e., intestinal immunity, secondary spread) outweighed the risk for vaccine-associated paralytic poliomyelitis (VAPP) (i.e., one case among 2.4 million vaccine doses distributed). In 1997, to decrease the risk for VAPP but maintain the benefits of OPV, ACIP recommended replacing the all-OPV schedule with a sequential schedule of IPV followed by OPV. Since 1997, the global polio eradication initiative has progressed rapidly, and the likelihood of poliovirus importation into the United States has decreased substantially. In addition, the sequential schedule has been well accepted. No declines in childhood immunization coverage were observed, despite the need for additional injections. On the basis of these data, ACIP recommended on June 17, 1999, an all-IPV schedule for routine childhood polio vaccination in the United States to eliminate the risk for VAPP. ACIP reaffirms its support for the global polio eradication initiative and the use of OPV as the only vaccine recommended to eradicate polio from the remaining countries where polio is endemic.     

脊髓灰质炎疫苗应用现状及免疫策略进展

1988年,全球消灭脊髓灰质炎（脊灰）倡议行动启动以来,取得了重大进展。2012年,全球报告脊灰223例,较2011年减少〉60%,本土脊灰流行国家减少为尼日利亚、巴基斯坦和阿富汗,脊灰野病毒（Wild Poliovirus,WPV）病例数下降到历史最低水平。但WPV传播仍未被阻断,无脊灰国家/地区仍面临输入WPV的风险。同时,有些国家正面临使用口服脊灰减毒活疫苗（Oral Poliomyelitis Attenuated Live Vaccine,OPV）所致疫苗衍生脊灰病毒的风险。目前,不同国家/地区评估各自的脊灰发病风险,依据OPV、脊灰病毒灭活疫苗（Inactivated Poliovirus Vaccine,IPV）的风险和收益,不同国家/地区采用不同的免疫策略：仅使用IPV、序贯使用IPV/OPV和仅使用OPV。2013年,世界卫生组织《全球消灭脊灰终结战略计划》中提出,2014年全球阻断WPV传播,2015年所有国家应至少使用1剂IPV,停用OPV中的Ⅱ型组分;2018年完成消灭WPV证实后,停用OPV。现对OPV和IPV的应用现状以及免疫策略进行简述。     

Cost analysis of post-polio certification immunization policies

OBJECTIVE: An analysis was conducted to estimate the costs of different potential post-polio certification immunization policies currently under consideration, with the objective of providing this information to policy-makers. METHODS: We analyzed three global policy options: continued use of oral poliovirus vaccine (OPV); OPV cessation with optional inactivated poliovirus vaccine (IPV); and OPV cessation with universal IPV. Assumptions were made on future immunization policy decisions taken by low-, middle-, and high-income countries. We estimated the financial costs of each immunization policy, the number of vaccine-associated paralytic poliomyelitis (VAPP) cases, and the global costs of maintaining an outbreak response capacity. The financial costs of each immunization policy were based on estimates of the cost of polio vaccine, its administration, and coverage projections. The costs of maintaining outbreak response capacity include those associated with developing and maintaining a vaccine stockpile in addition to laboratory and epidemiological surveillance. We used the period 2005-20 as the time frame for the analysis. FINDINGS: OPV cessation with optional IPV, at an estimated cost of US$ 20,412 million, was the least costly option. The global cost of outbreak response capacity was estimated to be US$ 1320 million during 2005-20. The policy option continued use of OPV resulted in the highest number of VAPP cases. OPV cessation with universal IPV had the highest financial costs, but it also had the least number of VAPP cases. Sensitivity analyses showed that global costs were sensitive to assumptions on the cost of the vaccine. Analysis also showed that if the price per dose of IPV was reduced to US$ 0.50 for low-income countries, the cost of OPV cessation with universal IPV would be the same as the costs of continued use of OPV. CONCLUSION: Projections on the vaccine price per dose and future coverage rates were major drivers of the global costs of post-certification polio immunization. The break-even price of switching to IPV compared with continuing with OPV immunizations is US$ 0.50 per dose of IPV. However, this doses not account for the cost of vaccine-derived poliovirus cases resulting from the continued use of OPV. In addition to financial costs, risk assessments related to the re-emergence of polio will be major determinants of policy decisions.     

The role of routine polio immunization in the post-certification era

The role of routine vaccination against poliomyelitis for the post-certification era remains an important area for policy decision-making. Two critical decisions need to be taken: first, to continue or discontinue vaccination with the live attenuated oral poliovirus vaccine (OPV); and second, if OPV is to be discontinued, whether vaccination with inactivated poliovirus vaccine (IPV) is needed. Four potential vaccination scenarios can be constructed: stop all polio vaccination; continue with current vaccination policies (OPV, IPV, or sequential schedule); discontinue OPV, but continue IPV universally; or discontinue OPV, but continue IPV in selected countries. All possible scenarios require continued investments in a surveillance and response strategy, including a stockpile of polio vaccine. Continuing vaccination would limit the savings that could be applied to the control of other health priorities. This report reviews the key issues associated with each scenario, highlights the advantages and disadvantages of each scenario, and outlines the major challenges for policy decision-making.     

A developing country perspective on vaccine-associated paralytic poliomyelitis

When the Expanded Programme on Immunization was established and oral poliovirus vaccine (OPV) was introduced for developing countries to use exclusively, national leaders of public health had no opportunity to make an informed choice between OPV and the inactivated poliovirus vaccine (IPV). Today, as progress is made towards the goal of global eradication of poliomyelitis attributable to wild polioviruses, all developing countries where OPV is used face the risk of vaccine-associated paralytic poliomyelitis (VAPP). Until recently, awareness of VAPP has been poor and quantitative risk analysis scanty but it is now well known that the continued use of OPV perpetuates the risk of VAPP. Discontinuation or declining immunization coverage of OPV will increase the risk of emergence of circulating vaccine-derived polioviruses (cVDPV) that re-acquire wild virus-like properties and may cause outbreaks of polio. To eliminate the risk of cVDPV, either very high immunization coverage must be maintained as long as OPV is in use, or IPV should replace OPV. Stopping OPV without first achieving high immunization coverage with IPV is unwise on account of the possibility of emergence of cVDPV. Increasing numbers of developed nations prefer IPV, and manufacturing capacities have not been scaled up, so its price remains prohibitively high and unaffordable by developing countries, where, in addition, large-scale field experience with IPV is lacking. Under these circumstances, a policy shift to increase the use of IPV in national immunization programmes in developing countries is a necessary first step; once IPV coverage reaches high levels (over 85%), the withdrawal of OPV may begin.     

产妇与婴儿脊髓灰质炎中和抗体水平变化特征分析

目的 评价脊髓灰质炎中和抗体在产妇及其婴儿体内消长规律,比较不同免疫程序下婴儿抗体水平变化。方法 选取2013年7月-2014年4月在广州市荔湾区妇幼保健院进行分娩的产妇及其新生儿作为研究对象,采用血清流行病学方法对产妇及产妇所生婴儿0（新生儿）、3、6月龄脊灰中和抗体水平进行分析;并根据婴儿基础免疫程序将其分为脊髓灰质炎减毒活疫苗（OPV）组、脊髓灰质炎灭活疫苗（IPV）与IPV+OPV 3组,比较疫苗接种后的抗体水平。结果 共采集179位产妇外周静脉血,婴儿0、3、6月龄时分别采血176、149、62份。新生儿较产妇I、II、III型脊灰中和抗体水平有所下降,3、6月龄时抗体水平均大幅上升,6月龄时各型分别高达607.0（95%CI=146.0~2 523.1）、239.6（95%CI=80.4~713.6）和235.9（95%CI=56.0~994.8）。OPV、IPV、IPV+OPV组在婴儿各个时间段脊灰I、II、III型抗体几何平均滴度倒数（GMRT）和抗体阳性率差异均无统计学意义（均P > 0.05）。产妇脊灰抗体水平与新生儿脊灰Ⅱ、III型母传抗体呈显著正相关关系（t_II=5.953、P=0.000,t_III=7.260、P < 0.001）。结论 新生儿脊灰胎传抗体水平较母体下降。IPV全程接种、IPV与OPV序贯免疫对婴儿均有较好的免疫原性,中国现阶段可大力推进IPV与OPV序贯免疫程序。     

The cost-effectiveness of alternative polio immunization policies in South Africa

AIMS: To assess the cost-effectiveness of switching from oral polio vaccine (OPV) to inactivated poliovirus vaccine (IPV), or to cease polio vaccination in routine immunization services in South Africa at the time of OPV cessation globally following polio eradication. METHODS: The cost-effectiveness of nine different polio immunization alternatives were evaluated. The costs of introducing IPV in a separate vial as well as in different combination vaccines were estimated, and IPV schedules with 2, 3 and 4 doses were compared with the current 6-dose OPV schedule. Assumptions about IPV prices were based on indications from vaccine manufacturers. The health impact of OPV cessation was measured in terms of vaccine associated paralytic paralysis (VAPP) cases and disability adjusted life years (DALYs) averted. CONCLUSIONS: The use of OPV in routine immunization services is predicted to result in 2.96 VAPP cases in the 2005 cohort. The cost-effectiveness of the different IPV alternatives varies between US$ 740,000 and US$ 7.2 million per VAPP case averted. The costs per discounted DALY averted amount to between US$ 61,000 and US$ 594,000. Among the IPV strategies evaluated, the 2-dose schedule in a 10-dose vial is the most cost-effective option. At the assumed vaccine prices, all IPV options do not appear to be cost-effective in the South African situation. OPV cessation without IPV replacement would result in cost savings of US$ 1.6 million per year compared to the current situation. This is approximately a 9% decrease in the budget for vaccine delivery in South Africa. However, with this option there is a risk (albeit small) of vaccine-derived poliovirus circulating in a progressively susceptible population. For IPV in a single dose vial, the break-even price, at which the costs of IPV delivery equal the current OPV delivery costs, is US$ 0.39.     

Intradermal fractional dose inactivated polio vaccine: a review of the literature

Oral polio vaccine (OPV) will likely be insufficient to completely eradicate polio due to its propensity to mutate into neurovirulent forms and its inability to produce adequate immunity in certain areas of the world. Inactivated polio vaccine (IPV), a killed vaccine which therefore cannot mutate, may be more effective than OPV in certain populations, and will likely be required for global polio eradication. However, the high cost of IPV is prohibitive in many areas of the world. Intradermal administration has the potential to lower the dose, and thus the cost, of IPV. This article reviews the clinical studies to date on intradermal fractional dose polio vaccination. We conclude that intradermal IPV vaccination shows potential as a means to reduce the cost and increase the ease of administration of IPV, but that additional research is needed to determine the optimal fractional dose, timing, and role of adjuvants in intradermal IPV vaccination as well as the clinical significance of different antibody titers above the threshold for seroconversion.     

A ten-year experience in control of poliomyelitis through a combination of live and killed vaccines in two developing areas.

We describe a successful program of poliomyelitis control using a combination of killed and live polio vaccines over a 10-year period in two developing areas, the West Bank and Gaza, adjacent to a relatively developed country, Israel. During the 1970s, immunization using live trivalent oral polio vaccine (OPV) in these areas covered more than 90 percent of the infant population. Nevertheless, the incidence of paralytic polio continued to be high, with many cases occurring in fully or partially immunized persons. It was thought that this could be due to interference with OPV take by other enteroviruses present in the environment due to poor sanitary conditions in these areas. A new policy combining five doses of OPV with two doses of inactivated polio vaccine (IPV) was adopted and implemented in 1978. In the 10 years since then, immunization coverage of infants increased to an estimated 95 percent and paralytic poliomyelitis has been controlled, despite exposure to wild poliovirus from neighboring countries including an outbreak in Israel in 1988. This experience suggests that wide coverage using the combination of IPV and OPV is an effective vaccination policy that may make eradication of polio possible even in developing areas.     

Inactivated polio vaccination using a microneedle patch is immunogenic in the rhesus macaque

The phased replacement of oral polio vaccine (OPV) with inactivated polio vaccine (IPV) is expected to significantly complicate mass vaccination campaigns, which are an important component of the global polio eradication endgame strategy. To simplify mass vaccination with IPV, we developed microneedle patches that are easy to administer, have a small package size, generate no sharps waste and are inexpensive to manufacture. When administered to rhesus macaques, neutralizing antibody titers were equivalent among monkeys vaccinated using microneedle patches and conventional intramuscular injection for IPV types 1 and 2. Serologic response to IPV type 3 vaccination was weaker after microneedle patch vaccination compared to intramuscular injection; however, we suspect the administered type 3 dose was lower due to a flawed pre-production IPV type 3 analytical method. IPV vaccination using microneedle patches was well tolerated by the monkeys. We conclude that IPV vaccination using a microneedle patch is immunogenic in rhesus macaques and may offer a simpler method of IPV vaccination of people to facilitate polio eradication.     

Adjuvants and inactivated polio vaccine: A systematic review

Poliomyelitis is nearing universal eradication; in 2011, there were 650 cases reported globally. When wild polio is eradicated, global oral polio vaccine (OPV) cessation followed by use of universal inactivated polio vaccine (IPV) is believed to be the safest vaccination strategy as IPV does not mutate or run the risk of vaccine derived outbreaks that OPV does. However, IPV is significantly more expensive than OPV. One strategy to make IPV more affordable is to reduce the dose by adding adjuvants, compounds that augment the immune response to the vaccine. No adjuvants are currently utilized in stand-alone IPV; however, several have been explored over the past six decades. From aluminum, used in many licensed vaccines, to newer and more experimental adjuvants such as synthetic DNA, a diverse group of compounds has been assessed with varying strengths and weaknesses. This review summarizes the studies to date evaluating the efficacy and safety of adjuvants used with IPV.     

Neutralization capacity of highly divergent type 2 vaccine-derived polioviruses from immunodeficient patients

The use of the oral poliovirus vaccine (OPV) in developing countries has reduced the incidence of poliomyelitis by >99% since 1988 and is the primary tool for global polio eradication. Spontaneous reversions of the vaccine virus to a neurovirulent form can impede this effort. In persons with primary B-cell immunodeficiencies, exposure to OPV can result in chronic infection, mutation, and excretion of immunodeficiency-associated vaccine-derived polioviruses, (iVDPVs). These iVDPVs may have the potential for transmission in a susceptible population and cause paralysis. The extent to which sera from OPV recipients are able to neutralize iVDPVs with varying degrees of antigenic site substitutions is investigated here. We tested sera from a population immunized with a combination vaccine schedule (both OPV and inactivated polio vaccine) against a panel of iVDPVs and found that increases in amino acid substitution in the P1 capsid protein resulted in a decrease in the neutralizing capacity of the sera. This study underscores the importance of maintaining high vaccine coverage in areas of OPV use as well as active surveillance of those known to be immunocompromised.     

Failure to detect infection by oral polio vaccine virus following natural exposure among inactivated polio vaccine recipients

While oral polio vaccine (OPV) has been shown to be safe and effective, it has been observed that it can circulate within a susceptible population and revert to a virulent form. Inactivated polio vaccine (IPV) confers protection from paralytic disease, but provides limited protection against infection. It is possible, then, that an IPV-immunized population, when exposed to OPV, could sustain undetected circulation of vaccine-derived poliovirus. This study examines the possibility of polio vaccine virus circulating within the United States (highly IPV-immunized) population that borders Mexico (OPV-immunized). A total of 653 stool and 20 sewage samples collected on the US side of the border were tested for the presence of poliovirus. All samples were found to be negative. These results suggest that the risk of circulating vaccine-derived poliovirus is low in fully immunized IPV-using populations in developed countries that border OPV-using populations.     

Oral poliomyelitis vaccine: time to change?

For 3 decades, vaccination against poliomyelitis has rested mainly on the use of the oral attenuated vaccine (OPV). In countries where wild type poliomyelitis has been successfully controlled by OPV, the rare cases of poliomyelitis that can still be identified occur in vaccinees or their contacts and are caused by vaccine related strains. Over years, data indicating that the inactivated vaccine (IPV) also has the potential to control poliomyelitis and that there are no known risks associated with the use of this vaccine have accumulated. The reasons for changes in vaccine policy in industrialised countries and the situation of the global effort of poliomyelitis immunisation are described. Some of the issues and challenges for the future are reviewed.     

Polio vaccination coverage and seroprevalence of poliovirus antibodies after the introduction of inactivated poliovirus vaccines for routine immunization in Japan

In Japan, the oral poliovirus vaccine (OPV) was changed to 2 types of inactivated poliovirus vaccine (IPV), the standalone conventional IPV (cIPV) and the Sabin-derived IPV combined with diphtheria-tetanus-acellular pertussis vaccine (DTaP-sIPV), for routine immunization in 2012. We evaluated polio vaccination coverage and the seroprevalence of poliovirus antibodies using data from the National Epidemiological Surveillance of Vaccine-Preventable Diseases (NESVPD) from 2011 to 2015. Several years before the introduction of IPV in 2012, OPV administration for children was refused by some parents because of concerns about the risk of vaccine-associated paralytic poliomyelitis. Consequently, in children aged <1?years who were surveyed in 2011–2012, polio vaccination coverage (45.0–48.8%) and seropositivity rates for poliovirus (type 1: 51.7–65.9%, type 2: 48.3–53.7%, and type 3: 15.0–29.3%) were decreased compared to those surveyed in 2009. However, after IPV introduction, the vaccination coverage (95.5–100%) and seropositivity rates (type 1: 93.2–96.6%, type 2: 93.1–100%, and type 3: 88.6–93.9%) increased among children aged <1?years in 2013–2015. In particular, seropositivity rates and geometric mean titers (GMTs) for poliovirus type 3 in <5-year-old children who received 4 doses of IPV (98.5% and 247.4, respectively) were significantly higher than in those who received 2 doses of OPV (72.5% and 22.9, respectively). Furthermore, in <5-year-old children who received 4 doses of either DTaP-sIPV or cIPV, the seropositivity rates and the GMTs for all 3 types of poliovirus were similarly high (96.5–100% and 170.3–368.8, respectively). Our findings from the NESVPD demonstrate that both the vaccination coverage and seropositivity rates for polio remained high in children after IPV introduction.     

Polio eradication in India: some observations

In 1988, the World Health Assembly passed resolution WHA 41.28, which committed the World Health Organization (WHO) to the global eradication of poliomyelitis by the year 2000. In spite of the combined efforts by UNICEF, National Polio Surveillance Project (NPSP), Indian Academy of Pediatrics (IAP) and Rotary International, Polio Free India is still a distant dream.Though oral polio vaccine has succeeded in polio eradication from many countries but there is high incidence of vaccine failure in India.Oral polio vaccine (OPV) has failed to provide full protection to many children who have developed paralytic polio even after taking 10 or more doses of OPV. In some children, OPV has caused paralysis-vaccine associated paralytic polio (VAPP). Number of children developing polio due to vaccine is high and on increase. Reasons for this could be that even immunocompromised children are being administered OPVbecause IPV is not available. Vaccine failure has exaggerated the problem of VAPP. No efforts have been made to find the causes for high incidence of vaccine failure and VAPP.     

Economics of polio vaccination in the post-eradication era: should OPV-using countries adopt IPV?

The continued use of oral polio vaccine (OPV) poses a threat to polio virus eradication. Stopping all polio vaccination in the post-certification era is no longer considered to be a practical option. Policy makers agree that OPV use must stop immediately after certification. Therefore, the pragmatic alternative is for the OPV-using countries to switch to IPV. This study estimates the cost of switching to IPV, and the cost-effectiveness of this switch. Using data on the number of polio cases and the number of unvaccinated children in different countries of the world, the risks of polio and polio outbreaks have been calculated. The current cost of routine and intensive OPV immunisation is about US $2143 million in the 148 OPV-using countries. Routine use of IPV in these countries should cost US $1246 million. If the current costs of routine and intensive polio immunisation are considered, adopting IPV to replace OPV will not increase the total global cost. Even if the cost of intensive polio immunisation is ignored, cost-effectiveness ratio of adopting IPV remains less than the average GNI per capita of OPV-using countries. The incremental cost of adopting IPV to replace OPV is relatively low, about US $1 per child per year, and most countries should be able to afford this additional cost.