Oral and fecal polio vaccine excretion following bOPV vaccination among Israeli infants

IntroductionInactivated polio virus (IPV) vaccinations are a mainstay of immunization schedules in developed countries, while oral polio vaccine (OPV) is administered in developing countries and is the main vaccine in outbreaks. Due to circulating wild poliovirus (WPV1) detection in Israel (2013), oral bivalent polio vaccination (bOPV) was administered to IPV primed children and incorporated into the vaccination regimen.ObjectivesWe aimed to determine the extent and timeframe of fecal and salivary polio vaccine virus (Sabin strains) shedding following bOPV vaccination among IPV primed children.MethodsFecal samples were collected from a convenience sample of infants and toddlers attending 11 Israeli daycare centers. Salivary samples were collected from infants and toddlers following bOPV vaccination.Results398 fecal samples were collected from 251 children (ages: 6–32 months), 168 received bOPV vaccination 4–55 days prior to sample collection. Fecal excretion continued among 80 %, 50 %, and 20 %, 2, 3, and 7 weeks following vaccination. There were no significant differences in the rate and duration of positive samples among children immunized with 3 or 4 IPV doses. Boys were 2.3-fold more likely to excrete the virus (p = 0.006). Salivary shedding of Sabin strains occurred in 1/47 (2 %) and 1/49 (2 %) samples 4, and 6 days following vaccination respectively.ConclusionsFecal detection of Sabin strains among IPV-primed children continues for 7 weeks; additional doses of IPV do not augment intestinal immunity; limited salivary shedding occurs for up to a week. This data can enhance understanding of intestinal immunity achieved by different vaccination schedules and guide recommendations for contact precautions of children following bOPV vaccination.     

武汉市洪山区二价脊髓灰质炎减毒活疫苗损耗系数分析

目的分析武汉市洪山区二价脊髓灰质炎减毒活疫苗(bOPV)损耗系数,了解其损耗原因及影响因素,为科学制定疫苗使用计划,规范疫苗管理提供依据。方法利用湖北省免疫规划信息系统及疫苗出入库管理系统等数据,设计专用调查表了解洪山区各预防接种单位bOPV接种及使用情况,采用描述性统计分析方法计算损耗系数。结果洪山区25家预防接种单位bOPV损耗系数为1.69。区卫计委直属门诊(1.35)和大型医院承办社区门诊(2.01)损耗系数之间的差异有统计学意义;bOPV接种周期1次/周(1.57)和2~6次/周(1.94)损耗系数之间的差异有统计学意义;疫苗启用废弃时间按<4 h(1.86)和>4 h(1.61)损耗系数之间的差异有统计学意义。做损耗系数相关因素的多因素回归分析发现,不同的门诊属性比接种周期和接种台数量对损耗因素的影响更大。2016和2017年损耗系数分别为2.09和1.75,经比较,两者差异有统计学意义。结论洪山区bOPV管理及使用比较规范,可通过加强监管考核、设置集中接种、规范宣传培训等手段进一步减少疫苗损耗。     

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.     

Refusal of oral polio vaccine in northwestern Pakistan: A qualitative and quantitative study

Background

Refusal of the oral polio vaccine (OPV) is a difficulty faced by the Polio Eradication Initiative (PEI) in multiple endemic areas, including the Khyber Pakhtunkhwa Province (KPP), Pakistan. In 2007, we investigated community perceptions of the OPV and estimated the prevalence of OPV refusal in three districts in Swat Valley, KPP, a polio-endemic area.

Methods

Qualitative data concerning community perceptions were collected by focus group discussions among lady health workers (LHWs) and mothers with children <1 year old and by key informant interviews with local health managers and officials. Quantitative data collection followed using a questionnaire survey of 200 LHWs and a cluster sampling survey of 210 mothers (per district) with children <1 year old.

Results

The qualitative assessments identified the grounded theory of OPV refusal involving facts known by the residents that are related to the OPV (too frequent OPV campaigns, an OPV boycott in northern Nigeria in 2003 and that birth control is viewed as is against Islam), the local interpretations of these facts (perceptions that OPV contained birth control or pork, that OPV was a foreign/central plot against Muslims, and that the vaccination was against the Hadith and the fate determined by God) and different manifestations of OPV refusal. Among the three districts studied, the proportion of LHWs who encountered OPV refusal ranged from 0 to 33%, whereas among the districts, the proportions of mothers unwilling to give OPV to their children ranged from 0.5 to 5.7%. Refusal of other injectable vaccines was almost equally prevalent for reasons that were very similar.

Conclusions

The PEI needs to reflect local value system in the path to polio eradication in the studied districts in the Swat Valley. The religious and cultural values as well as the interpretation of the international political situation are of particular importance.     

新型Ⅱ型口服脊髓灰质炎减毒活疫苗研究进展

全球消灭脊髓灰质炎行动(GPEI)于2016年4月调整脊髓灰质炎疫苗免疫接种战略,将三价口服脊髓灰质炎疫苗(tOPV)转换为二价口服脊髓灰质炎疫苗(bOPV),并在全球全面撤出Ⅱ型口服脊髓灰质炎减毒活疫苗(OPVⅡ)。然而在OPVⅡ撤出以后,亚洲和非洲多地暴发Ⅱ型循环疫苗衍生脊髓灰质炎病毒(cVDPVⅡ)。为了彻底消灭脊髓灰质炎病毒,GPEI于2010年启动研发新型Ⅱ型口服脊髓灰质炎减毒活疫苗(nOPVⅡ),并于近年开始考虑是否有必要重启OPV。本文概述了OPVⅡ撤出前后cVDPVⅡ的流行病学情况,影响OPV重启的相关因素以及nOPVⅡ相关研究进展。     

Impact of enterovirus and other enteric pathogens on oral polio and rotavirus vaccine performance in Bangladeshi infants

BackgroundOral polio vaccine (OPV) and rotavirus vaccine (RV) exhibit poorer performance in low-income settings compared to high-income settings. Prior studies have suggested an inhibitory effect of concurrent non-polio enterovirus (NPEV) infection, but the impact of other enteric infections has not been comprehensively evaluated.MethodsIn urban Bangladesh, we tested stools for a broad range of enteric viruses, bacteria, parasites, and fungi by quantitative PCR from infants at weeks 6 and 10 of life, coincident with the first OPV and RV administration respectively, and examined the association between enteropathogen quantity and subsequent OPV serum neutralizing titers, serum rotavirus IgA, and rotavirus diarrhea.ResultsCampylobacter and enterovirus (EV) quantity at the time of administration of the first dose of OPV was associated with lower OPV1-2 serum neutralizing titers, while enterovirus quantity was also associated with diminished rotavirus IgA (−0.08 change in log titer per tenfold increase in quantity; P = 0.037), failure to seroconvert (OR 0.78, 95% CI: 0.64–0.96; P = 0.022), and breakthrough rotavirus diarrhea (OR 1.34, 95% CI: 1.05–1.71; P = 0.020) after adjusting for potential confounders. These associations were not observed for Sabin strain poliovirus quantity.ConclusionIn this broad survey of enteropathogens and oral vaccine performance we find a particular association between EV carriage, particularly NPEV, and OPV immunogenicity and RV protection. Strategies to reduce EV infections may improve oral vaccine responses.ClinicalTrials.gov Identifier: NCT01375647.     

FlaC supplemented with VAA,OmpK or OmpR as bivalent subunit vaccine candidates induce immune responses against Vibrio anguillarum in flounder (Paralichthys olivaceus)

In our previous study, ten candidate proteins have been identified with immunogenicity and protection against Vibrio anguillarum in flounder (Paralichthys olivaceus). Among them, FlaC is the important outer protein in the flagellum with immunogenicity; VAA, OmpK and OmpR are protection proteins against V. anguillarum. In this paper, FlaC supplemented with VAA, OmpK or OmpR as bivalent subunit vaccine candidates, and their immune response of flounder and protective effects were evaluated, respectively. Recombinant(r) proteins of FlaC were mixed with rVAA, rOmpK and rOmpR, respectively, rVAA + rFlaC (AF), rOmpK + rFlaC (KF) and rOmpR + rFlaC (RF); formalin-killed cells (FKC) or PBS were injected to flounder, respectively. After immunization, the percentages of CD3⁺ T lymphocytes and surface membrane immunoglobulin-positive (sIg⁺) B lymphocytes in peripheral blood lymphocytes (PBLs), total antibodies (TA), specific antibodies against V. anguillarum (VA), specific antibodies against bivalent recombinant proteins (PA), the expression of immune-related genes and relative percent survivals (RPS) were measured, respectively. The results showed that three bivalent vaccines candidates and FKC could induce the proliferation of sIg⁺ B lymphocytes and CD3⁺ T lymphocytes in PBLs. The TA, VA and PA induced in bivalent vaccines candidates and FKC groups were significantly higher than that of the control group. CD3, IgM, CD4-1, CD4-2, CD8α and CD8β genes were up-regulated. After challenge with V. anguillarum, RPS in AF, KF, RF and FKC groups exhibited 62.6 ± 2.33%, 78.95 ± 3.01%, 75.45 ± 0.97%, and 56.71 ± 2.15% respectively. The results revealed that three bivalent vaccines candidates and FKC could induce the immune response in flounder, and have good protection against V. anguillarum, and KF can be an efficient bivalent subunit vaccine candidate.     

No effect of oral polio vaccine administered at birth on mortality and immune response to BCG. A natural experiment

Background

WHO recommends oral polio vaccine at birth (OPV0) in polio endemic countries. During a period without OPV in Guinea-Bissau in 2004, we observed that not receiving OPV0 was associated with significantly decreased mortality in boys and better immune response to BCG vaccination. In 2007, whilst conducting a trial of BCG and vitamin A supplementation (VAS) at birth to low birthweight (LBW) children, OPV was again lacking for a short period. We used this natural experiment to test the previous observations.

Methods

In the trial LBW infants were randomised to early or delayed BCG and VAS or placebo at birth. We noted whether the children received OPV0 or not. We compared children who received No OPV0 with those who received OPV0 in the 2 months before and the 2 months after the period without OPV. Mortality was compared in Cox regression models providing adjusted hazard ratios (aHR); the immune response to BCG was assessed in Poisson models providing adjusted prevalence ratios (aPR).

Results

Ninety-nine children received No OPV0 and were compared with 243 children who received OPV0. No OPV0 was associated with insignificantly higher mortality during the first year of life, the aHR being 1.83 (95% CI: 0.93–3.61). The effect was similar in boys and girls. Overall, there was no significant association between No OPV0 and having a positive PPD response (aPR = 1.33 (0.64–2.78)) or a scar (aPR = 1.02 (0.93–1.11)) after BCG vaccination, though No OPV0 boys were more likely to develop a scar (aPR: 1.10 (1.01–1.20)).

Conclusions

The findings did not support our previous observation that not receiving OPV0 was associated with reduced mortality in boys. The findings weakly supported that OPV0 leads to a dampened response to simultaneously administered BCG vaccine in boys.     

双价肾综合征出血热疫苗人群接种反应与免疫学效果观察

观察HFRS沙鼠肾细胞灭活疫苗对非疫区人群的接种反应与免疫学效果。方法：进行荧光抗体及中和抗体检测。结果：疫苗接种1～3针后，轻度体温反应率分别为2.50％、0．63％、1．25％；轻度红肿反应率分别为0.00％、1.88％、1．25％；648名接种者均无严重反应和异常反应。全程接种后2周，荧光抗体阳转率为100％（83／83）；中和抗体总阳转率亦为100％（53／53），其中Ⅰ型为86．8％（46／53），Ⅱ型为962％（51／53）。结论：（1）该疫苗副反应轻，副反应率低，安全性好；（2）免疫效果良好。     

Lack of association between intussusception and oral polio vaccine in Cuban children

Two exploratory investigations found an increased risk of intussusception after oral polio vaccine (OPV). A large, national, population-based study was undertaken in Cuba to investigate a possible association. Three hundred and thirty-five cases of intussusception in children under 2 years of age occurring in 1995–2000 were identified and their OPV records retrieved. The relative incidence (RI) of intussusception in defined periods up to 42 days after OPV in children under 1 year was estimated using the self-controlled case series method, controlling for age and season. The RI was not significantly raised in any of the time intervals examined within the 0–42 day period after OPV. For the period 0–42 days as a whole the RI was 1.11, 95% CI 0.74–1.67. This study does not support the hypothesis that OPV causes intussusception.     

Transplacental rotavirus IgG interferes with immune response to live oral rotavirus vaccine ORV-116E in Indian infants

The lower immune response and efficacy of live oral rotavirus (RV) vaccines tested in developing countries may be due in part to high levels of pre-existing RV antibodies transferred to the infant from mother via the placenta. The candidate RV vaccine strain 116E was isolated from a newborn indicating that it might grow well even in the presence of this transplacental rotavirus antibody. Since the immune response to this vaccine among infants in the Indian subcontinent has been greater than that of the commercially licensed vaccines, we questioned whether this might be due to the ability of RV 116E to grow well in infants despite the presence of maternal RV antibody. To this end, we tested pre-immunization sera from Indian infants enrolled in a phase Ia/IIb trial of candidate RV vaccine ORV-116E for transplacental RV IgG to see whether it affected the immune responses and seroconversion to the vaccine. We found that the high titers of transplacental RV IgG diminished the immune responses of infants to ORV-116E vaccine. However, the vaccine was able to overcome the inhibitory effect of this RV IgG in a dose-dependent manner. This report clearly demonstrates the interference of maternal antibody on RV vaccine immunogenicity in infants in a field study as well as the ability of ORV-116E to overcome this interference when used at a higher dose.     

Sabin株脊髓灰质炎灭活疫苗与不同剂型Ⅰ型Ⅲ型脊髓灰质炎减毒活疫苗序贯接种的抗体滴度比较

目的  比较Sabin株脊髓灰质炎灭活疫苗(Sabin strain-based inactivated poliovirus vaccine,sIPV)与不同剂型Ⅰ型Ⅲ型脊髓灰质炎减毒活疫苗(bivalent types Ⅰ and Ⅲ oral poliovirus vaccine,bOPV)序贯接种的抗体滴度。 方法  选择柳州400名2月龄婴儿,按1：1：1：1随机分为sIPV+2bOPV糖丸、sIPV+2bOPV液体、2sIPV+bOPV糖丸、2sIPV+bOPV液体4组,按0 d、28 d、56 d免疫程序接种疫苗。检测免前、免后28 d脊灰中和抗体滴度。 结果  序贯程序相同时,1剂sIPV糖丸组与液体组免后Ⅰ型抗体滴度分布差异有统计学意义(Z=-2.589,P=0.010),Ⅱ型(Z=-0.331,P=0.741)和Ⅲ型(Z=-1.556,P=0.120)差异均无统计学意义(均有P>0.05);2剂sIPV糖丸组与液体组免后Ⅰ型(Z=-1.249,P=0.212)、Ⅱ型(Z=-1.658,P=0.097)和Ⅲ型(Z=-1.436,P=0.151)抗体滴度分布差异均无统计学意义(均有P>0.05)。剂型相同时,2剂sIPV组与1剂sIPV组各型抗体滴度分布差异均有统计学意义(均有P < 0.05)(1剂sIPV液体组与2剂sIPV液体组：Ⅰ型：Z=-2.766,P=0.006;Ⅱ型：Z=-9.137,P < 0.001;Ⅲ型：Z=-5.529,P < 0.001。1剂sIPV糖丸组与2剂sIPV糖丸组：Ⅰ型：Z=-3.748,P < 0.001;Ⅱ型：Z=-7.660,P < 0.001;Ⅲ型：Z=-6.030,P < 0.001)。 结论  bOPV糖丸和液体剂型免疫效果相似,各地接种部门应结合疫苗效果、接种对象特征和人口密度,选择适宜剂型接种;如sIPV供应充足,建议优先选择2剂sIPV序贯程序完成脊灰基础免疫接种。     

The muscle findings in a pediatric patient with live attenuated oral polio vaccine-related flaccid monoplegia

A pediatric patient, who was given live-attenuated oral polio vaccine twice without distinct gait disturbance during infancy, begun to present limp at 3 years. His gait disturbance became remarkable with aging. At 7 years, he was unable to dorsiflex the left ankle, and presented flaccid monoplegia of the left lower extremity, and the left Achilles tendon reflex was diminished. Magnetic resonance imaging revealed multiple crack-lines in the left anterior tibial muscle, but was unable to detect any distinct lesion at responsible level of L4, L5 and S1 anterior horn cells’ degeneration. Electromyography showed continuous fibrillation potentials, but muscle biopsy presented nearly normal in this muscle. The serum levels of polio antibody type 1 and type 2 titers were elevated 64× respectively, while the type 3 antibody titer was not elevated 4×. This patient was diagnosed as live attenuated oral polio vaccine-related flaccid monoplegia, with mild clinical course.     

Generation and evaluation of a recombinant Newcastle disease virus expressing the glycoprotein (G) of avian metapneumovirus subgroup C as a bivalent vaccine in turkeys

Virulent strains of Newcastle disease virus (NDV) and avian metapneumovirus (aMPV) can cause serious respiratory diseases in poultry. Vaccination combined with strict biosecurity practices has been the recommendation for controlling both NDV and aMPV diseases in the field. In the present study, an NDV based, LaSota strain recombinant vaccine virus expressing the glycoprotein (G) of aMPV subgroup C (aMPV-C) was generated as a bivalent vaccine using a reverse genetics approach. The recombinant virus, rLS/aMPV-C G was slightly attenuated in vivo, yet maintained similar growth dynamics, cytopathic effects, and virus titers in vitro when compared to the parental LaSota virus. Expression of the aMPV G protein in rLS/aMPV-C G-infected cells was detected by immunofluorescence assay. Vaccination of turkeys with one dose of rLS/aMPV-C G induced moderate aMPV-C-specific immune responses and comparable NDV-specific serum antibody responses to a LaSota vaccination control. Partial protection against pathogenic aMPV-C challenge and complete protection against velogenic NDV challenge was conferred. These results suggest that the LaSota recombinant virus is a safe and effective vaccine vector and that expression of the aMPV-C G protein alone is not sufficient to provide full protection against an aMPV-C infection. Expression of other immunogenic protein(s) of the aMPV-C virus alone or in conjunction with the G protein may be needed to induce a stronger protective immunity against the aMPV-C disease.     

不同免疫程序HFRS双价灭活疫苗免疫效果观察

目的：观察不同免疫程度肾综合征出血热（HFRS）双价灭活疫苗的免疫效果，确定最佳免疫方案。方法：采用流行病学实验方法，将158名10-12岁儿童随机分组后按不同免疫程序进行免疫，基础免疫后0.5个月、6个月、12个月、24个月及2年加强免疫后0.5个月采血检测HFRS荧光抗体及中和抗体。结果：2针（0，14d）与3针（0，7，28d）组间、2针加强（0，14d，6个月）与3针加强（0，7，28d，6个月）组间荧光抗体及中和抗体阳性率及GMT比无显性差异；6个月加强1针在免后12-24月中，荧光抗体阳性率高于未加强组，短期 （2年内）效果优于未加强组；免疫2年加强免疫后0.5个月，4组荧光抗体及中和抗体阳性率迅速上升至96.55％-100.0％。结论：既定3针基础免疫程序可简化为2针；6个月进行加强免疫为宜。     

Immune response to an intercalated enhanced inactivated polio vaccine/oral polio vaccine programme in Israel: impact on the control of poliomyelitis

A combined enhanced inactivated polio vaccine (EIPV) and oral polio vaccine (OPV) programme was introduced in Israel in 1990, with the purpose of providing a solution to the persistent polio morbidity in spite of a 30 year long OPV programme. The schedule comprised two doses of EIPV administered at the age of 2 and 4 months, intercalated with two doses of OPV at 4 and 6 months, followed by a reinforcing dose with the two vaccines simulltaneously administered at 12 months. The 5-year evaluation of the programme included: the assessment of clinical suspicions of polio, early immune response in successive cohorts administered the new schedule, dynamics of the immune profile in a cohort followed up to the age of 5, and monitoring of wild poliovirus excretion in sewage specimens collected in 25 permanent sites throughout Israel as well as from the Palestinian Authority. No paralytic polio cases associated with a wild or vaccinal poliovirus strain were detected since the introduction of the programme. At the age of 4 months, one week after administration of the second EIPV and first OPV dose, 100% seropositivity and high geometric mean titres (GMTs) of neutralizing antibody (NA) to the three vaccinal and to the wild poliovirus type 1, responsible for the 1988 polio outbreak, were observed. No change in percent of seropositivity occurred between the age of 6 and 12 months. Thirty days after the IPV and OPV reinforcing doses, GMTs to each of the four poliovirus strains were ≥3037. Up to the age of 5, the seropositivity was unchanged. After a 2.5–10-fold decline in the first year following the completion of the programme, GMTs to the three vaccinal and the wild poliovirus strain levelled off at rather high values, considered protective. Between 1990 and 1995, 16 wild poliovirus type 1 strains were isolated in three separate episodes in Gaza Strip sewage and once only in one Israeli site very close to Gaza City. The rapidly established, high and persistent NA titre to the vaccinal and wild poliovirus strains and the presence of immunological memory are indicative of high individual protection throughout the first 5 years of life. The only one-time introduction, without circulation, of a wild poliovirus strain in a single Israeli settlement suggests community protection. The intercalated programme offers a contribution to polio eradication by providing a solution to the primary and secondary failure associated with POV, as well as to the control of vaccine-associated paralytic poliomyelitis.     

Efficacy of an inactivated bivalent vaccine for enterovirus 71 and coxsackievirus A16 in mice immunized intradermally

Human hand, foot, and mouth disease (HFMD), an important infectious disease in children, is caused mainly by enterovirus 71 (EV71) and coxsackievirus A16 (CA16). In this study, a bivalent inactivated EV71/CA16 vaccine is developed and evaluated in immunized BALB/c mice injected through the intradermal route. Q-RT-PCR detection of the mRNA of immune signal molecules in local epithelial tissues inoculated with the vaccine indicates activation of innate immunity, which includes upregulation of immune-related chemokines, interferons and CD molecules. Further, the finding that neutralizing antibodies and specific T cellular responses were elicited in adult mice after two immunizations with the vaccine at a 28-day interval, which endowed offspring mice to defend a viral challenge, suggests the successful induction of specific protective antiviral immunity. All these data suggest that immunization with this bivalent EV71/CA16 vaccine via the intradermal route elicits effective immunity against EV71 and CA16 infection.     

Oral polio vaccine response in the MAL-ED birth cohort study: Considerations for polio eradication strategies

Background

Immunization programs have leveraged decades of research to maximize oral polio vaccine (OPV) response. Moving toward global poliovirus eradication, the WHO recommended phased OPV-to-IPV replacement on schedules in 2012. Using the MAL-ED prospective birth cohort data, we evaluated the influence of early life exposures impacting OPV immunization by measuring OPV response for serotypes 1 and 3.