Attenuated Polio Vaccine Research Articles

Comparative Study on MNVT of OPV Type I and III Reference Products in Different Periods

Widespread vaccination using the oral live attenuated polio vaccine (OPV) and Sabin strain inactivated vaccine (sIPV) have greatly reduced the incidence of polio worldwide. In the period post-polio, the virulence of reversion of the Sabin strain makes the use of OPV gradually becoming one of the major safety hazards. The verification and release of OPV has become the top priority. The monkey neurovirulence test (MNVT) is the gold standard for detecting whether OPV meets the criteria, which are recommended by the WHO and Chinese Pharmacopoeia. Therefore, we statistically analyzed the MNVT results of type I and III OPV at different stages: 1996-2002 and 2016-2022. The results show that the upper and lower limits and C value of the qualification standard of type I reference products in 2016-2022 have decreased compared with the corresponding scores in the 1996-2002 period. The upper and lower limit and C value of the qualified standard of type III reference products were basically the same as the corresponding scores in the 1996-2002. We also found significant differences in the pathogenicity of the type I and III in the cervical spine and brain, with the decreasing trend in the diffusion index of the type I and type III in the cervical spine and brain. Finally, two evaluation criteria were used to judge the OPV test vaccines from 2016 to 2022. The vaccines all met the test requirements under the evaluation criteria of the above two stages. Based on the characteristics of OPV, data monitoring was one of the most intuitive methods to judge changes in virulence.

Effects of live attenuated polio vaccine on the immunogenicity of live attenuated rotavirus vaccine

Objective To evaluate whether simultaneous vaccination with live attenuated polio vaccine affects the immunogenicity of live attenuated rotavirus (RV) vaccine. Methods Rotarix produced by GlaxoSmithKline was used as the research object. Two doses of Rotarix were orally administered on day 0 and month 1, and oral live attenuated polio vaccine (OPV) was administered on day 0, month 1 and month 2 according to the national vaccination plan. Healthy infants aged 6 to 16 weeks were randomly divided into two groups: interval vaccination group (Rotarix and OPV were vaccinated on different days) and simultaneous vaccination group (Rotarix and OPV were vaccinated on the same day). Serum samples were collected on day 0, month 2 and month 12, and serum RV-IgA was measured by enzyme linked immunosorbent assay. Statistical analysis was performed to evaluate whether there were statistical differences in the seroconversion rate and level distribution of RV-IgA between the two groups. Results The seroconversion rate of serum RV-IgA in month 2 was 73.84% in the interval vaccination and 63.95% in the simultaneous vaccination group, and the difference between them was statistically significant (P 0.05). Compared with the simultaneous vaccination group, the seroconversion rate and GMC of serum RV-IgA in month 12 were higher in the interval vaccination group, and the differences were statistically significant (P<0.05). Conclusions Simultaneous vaccination with live attenuated polio vaccine would affect the immune response of live attenuated rotavirus vaccine, especially the maintenance of RV-IgA antibody level. Key words: Poliovirus; Rotavirus; Vaccine; Immunogenicity

Vacinas Vivas em Crianças com Síndrome de DiGeorge/Deleção 22q11.2

Children with DiGeorge syndrome/chromosome 22q11.2 deletion syndrome might have a variable degree of immunodeficiency, which may limit the use of live vaccines. The aim of this study was to review the adverse effects of live vaccines and possible relation with immune status in patients with DiGeorge Syndrome/partial 22q11.2 deletion syndrome. Retrospective study with analysis of the clinical records of children with chromosome 22q11.2 deletion syndrome and DiGeorge syndrome phenotype, followed in a Primary Immunodeficiency center. Data were collected on: demographic characteristics; medical and vaccination history with live vaccines; T-CD4+ lymphocyte counts and lymphocyte proliferative responses to antigens and mitogens; adverse reactions; vaccine failure. Twenty three children with DiGeorge syndrome/22q11.2 deletion syndrome were included, 65.2% male, with average age at diagnosis of 11.3 months. Eighteen children (78%) received bacillus Calmette-Guérin vaccine: all with evidence of thymic activity; three presented moderate T-CD4+ lymphopenia and abnormal lymphocyte proliferative responses; one had abnormal lymphocyte proliferative responses for mitogens, four for purified protein derivative and one for tetanus toxoid. Measles, mumps and rubella vaccine was administered to 15 children, three of them with moderate immunosuppression and abnormal lymphocyte proliferative responses. Live attenuated polio vaccine was administered to 4 children without immunosuppression and the rotavirus vaccine to three children, one with moderate immunosuppression. No significant adverse reactions were reported. These data are in line with the findings of other international studies. In our sample, live vaccines were well-tolerated, even in children with moderate T-CD4+ lymphopenia and abnormal lymphocyte proliferative responses to antigens/mitogens.

MHC-II Deficiency Among Egyptians: Novel Mutations and Unique Phenotypes

MHC class II deficiency leads to defective CD4+ T-cell function that results from impaired antigen presentation. A genetic disorder in 1 of 4 genes results in this syndrome that is associated with the clinical phenotype of combined immunodeficiency. To describe the clinical, immunological, and molecular characteristics of 10 Egyptian patients from 9 different families having presented with MHC class II deficiency between 2012 and2017. An initial diagnosis based on the combination of clinical features and low HLA-DR expression by flow cytometry was confirmed by genetic analyses. Symptoms included failure to thrive (n= 9), persistent diarrhea (n= 5), and pneumonia (n= 8). Septicemia due to coagulase-negative staphylococci (n= 1) and Candida krusei (n= 1) was diagnosed. Nine patients orally received the live attenuated polio vaccine, of whom 3 developed acute flaccid paralysis thereafter. Nine patients received the BCG vaccine and none developed obvious signs of BCGitis. Four patients carried RFXANK gene mutations, 3 carried RFX5 gene mutations, 1 carried a CIITA gene mutation, and none carried RFXAP gene mutations. Six of the 7 detected mutations were previously unreported mutations: c.431T>C, c.247_250delTCAG, and c.600delG in the RFXANK gene; c.116+1G>A and c.715C>T in the RFX5 gene; and c.929delA in the CIITA gene. Given that Egypt is a North African country with a high rate of consanguinity, MHC class II deficiency is not rare. However, the molecular defects differ from those reported in nearby countries. Early diagnosis must be based on suspicious clinical signs and laboratory diagnosis because the defect can be missed by T-cell receptor excision circles based on neonatal screening.

Seronegativity to polio viruses among previously immunized adult candidates to solid organ transplantation

In the current effort to eliminate polio from the world, it is important to recognize and vaccinate susceptible groups, especially immunocompromised patients living in countries where attenuated polio vaccine is still used. In this report, we describe the frequency of protective antibodies in a small sample of adult SOT candidates in whom previous vaccination could be ascertained. Patients included in this report were selected among the participants of an ongoing prospective study carried out at the Reference Center for Special Immunobiologicals of the Evandro Chagas National Institute of Infectious Diseases in Rio de Janeiro, Brazil. Among the first 100 patients enrolled in this study, only seven adult SOT candidates had proven polio vaccination at childhood. Three of these seven patients (43%) had no protective antibody titers to one or more poliovirus subtype before solid organ transplant. Proven childhood vaccination against polio does not reliably provide lifelong protective antibody titers for adult SOT candidates and should not be used as a criterion to analyze the need for vaccination in this population.

The Importance of Social Networking in a National Polio Vaccine Campaign.

* Abbreviations: bOPV — : bivalent live oral attenuated polio vaccine IPV — : inactivated polio vaccine OPV — : oral polio vaccine WPV1 — : wild poliovirus type 1 The May 28, 2013 isolation of wild poliovirus type 1 (WPV1) in routine sewage samples signaled the beginning of the first protracted incident of WPV1 transmission in Israel since 1988. A door-to-door catch-up vaccination program with inactivated polio vaccine (IPV) was initiated in the area where the isolations were first identified. Although no cases of paralytic illness were diagnosed, evidence of continued and widespread transmission among children <9 years old necessitated the reintroduction of live oral attenuated polio vaccine in a country-wide campaign on August 18.1 To maximize safety, the bivalent live oral attenuated polio vaccine (bOPV) used in 2013 was given only to children previously immunized with IPV.2 The campaign was accompanied by extensive public discussion, particularly in the online social networks. The authors describe their experience answering vaccine-related questions online from June through October 2013, 1 (K.L.) as a volunteer and the other (L.R.) as a representative of the Ministry of Health. The campaign posed several challenges to winning public confidence: the reintroduction of a previously discontinued vaccine, the silent nature of the transmission, and the targeting of children who were already protected to protect others.1 Initially, the Ministry of Health allocated resources to traditional media to address these issues; the social networks were neglected. Meanwhile, individuals and groups with an antivaccine agenda began in June to flood the Hebrew-language Internet with postings that denied the significance of WPV1 in the sewage, decried the use of live vaccine, and rallied to stop the “dangerous” campaign. The Ministry of Health opened a dedicated Web site to address public concerns, but more was needed in the age of social networking. Between … Address correspondence to Keren Landsman, MD, MPH, Department of Community Medicine, Lady Davis Carmel Medical Center, 7th Michal St, Haifa, Israel, 3436212. E-mail: kerenlandsman{at}clalit.org.il

Alternative inactivated poliovirus vaccines adjuvanted with Quillaja brasiliensis or Quil-a saponins are equally effective in inducing specific immune responses.

Inactivated polio vaccines (IPV) have an important role at the final stages of poliomyelitis eradication programs, reducing the risks associated with the use of attenuated polio vaccine (OPV). An affordable option to enhance vaccine immunogenicity and reduce costs of IPV may be the use of an effective and renewable adjuvant. In the present study, the adjuvant activity of aqueous extract (AE) and saponin fraction QB-90 from Quillaja brasiliensis using poliovirus antigen as model were analyzed and compared to a preparation adjuvanted with Quil-A, a well-known saponin-based commercial adjuvant. Experimental vaccines were prepared with viral antigen plus saline (control), Quil-A (50 µg), AE (400 µg) or QB-90 (50 µg). Sera from inoculated mice were collected at days 0, 28, 42 and 56 post-inoculation of the first dose of vaccine. Serum levels of specific IgG, IgG1 and IgG2a were significantly enhanced by AE, QB-90 and Quil-A compared to control group on day 56. The magnitude of enhancement was statistically equivalent for QB-90 and Quil-A. The cellular response was evaluated through DTH and analysis of IFN-γ and IL-2 mRNA levels using in vitro reestimulated splenocytes. Results indicated that AE and QB-90 were capable of stimulating the generation of Th1 cells against the administered antigen to the same extent as Quil-A. Mucosal immune response was enhanced by the vaccine adjuvanted with QB-90 as demonstrated by increases of specific IgA titers in bile, feces and vaginal washings, yielding comparable or higher titers than Quil-A. The results obtained indicate that saponins from Q. brasiliensis are potent adjuvants of specific cellular and humoral immune responses and represent a viable option to Quil-A.

Oral poliovirus vaccine type 3 from a patient with transverse myelitis is neurovirulent in a transgenic mouse model

Background It is accepted that oral poliovirus vaccine (OPV) can cause vaccine-associated paralytic poliomyelitis (VAPP) and that wild poliovirus infection can rarely present as transverse myelitis. It is therefore possible that OPV could cause transverse myelitis. We previously reported a case of transverse myelitis that developed in a 6-month-old boy, 7 days after receiving his second dose of OPV. Objectives Our aim was to test the virus from this patient with transverse myelitis for neurovirulence in a mouse model. Study design The TgPVR21 transgenic mouse line, which expresses the human poliovirus receptor CD155, was used to assess neurovirulence of the viruses tested. Neurovirulence was expressed as the PD 50, the dose of virus causing paralysis in 50% of the mice. Four type 3 polioviruses were tested: a prototype wild strain, a fully attenuated polio vaccine virus, a virus from a patient with VAPP and the virus from the patient with transverse myelitis. Results The PD 50 for the wild poliovirus strain was 3.83 and for the fully attenuated vaccine strain, 7.63. The PD 50 for the two clinical isolates were between these values, ≧4.96 for the poliovirus known to have caused VAPP and ≧4.81 for the virus from the patient with transverse myelitis. Conclusions The report of an OPV strain from a transverse myelitis case being neurovirulent in an in vivo mouse model provides further evidence for a causal association between OPV and transverse myelitis.

Live attenuated polio vaccine and the risk of intussusception.

Since suspicion has been raised that administration of an oral live attenuated rotavirus vaccine may increase the risk of intussusception in young children, there has been concern about the possible effects of oral polio vaccine. The aim of the study was to evaluate the relationship between oral attenuated polio vaccine and intussusception in children below the age of 1 year. We conducted a nested case-control analysis based on data from the General Practice Research Database which encompassed 133 children who developed documented intussusception during the first year of life and 515 controls. The time from oral polio vaccine to the index date was similar in cases and controls. Relative risk estimates for intussusception ranged from 0.7 (95% CI 0.2, 2.1) for babies whose last oral polio vaccine was given 29-35 days before their index date to 1.0 (95% CI 0.4, 2.3) for those whose last oral polio vaccine was given 15-21 days before their index date (compared with babies vaccinated more than 43 days before their index date). There is no suggestion that oral polio vaccine increases the risk for intussusception.

Avaliação da taxa de cobertura vacinal no Centro de Saúde de Braga, nas coortes de nascimento de 1990 a 2005

Objectivo: Determinar a taxa de cobertura vacinal de cada uma das vacinas incluidas no Programa Nacional de Vacinacao (PNV), nas coortes de nascimento de 1990 a 2005, no Centro de Saude Braga (CSB) e nas suas Extensoes de Saude (ES). Tipo de estudo: Estudo observacional, descritivo e transversal. Local: Centro de Saude de Braga. Populacao: Utentes inscritos em cada uma das ES e US do CSB, nascidos entre o ano de 1990 e 2005. Metodos: Como fonte de informacao utilizou-se o modulo Estatisticas - Vacinas do programa informatico SINUS. Resultados: Foram alcancadas taxas de cobertura vacinal superiores a 95% em 2002 na vacina atenuada contra a poliomielite (VAP) e vacina contra a hepatite B (VHB), em 2004 na vacina contra o bacilo Calmette-Guerin (BCG) e vacina contra o sarampo-parotidite epidemica-rubeola (VASPR), e em 2005 na vacina contra a difteria-tetano-tosse convulsa (DTP) e vacina contra o Haemophilus influenzae b (Hib). Relativamente a vacina contra o tetano e a difteria (Td), de imunidade individual, a taxa de cobertura vacinal e sempre inferior a 100% (varia de 84 a 94%). Algumas ES mantem taxas de cobertura vacinal muitissimo inferiores ao recomendado. Verifica-se, tambem, que as taxas de cobertura vacinal sao mais baixas para as vacinas cujo PNV preve um maior numero de inoculacoes, tais como a DTP e a Hib. Conclusoes: Verifica-se uma tendencia progressiva de melhoria das taxas de cobertura vacinal ao nivel do CSB. Contudo, foram atingidos valores superiores a 95% somente muito recentemente. Assim, para a globalidade de utentes do CSB, os objectivos definidos no PNV comecam a ser cumpridos de forma aceitavel nas coortes de nascimento mais novas. Salienta-se tambem a existencia de importantes assimetrias na taxa de cobertura vacinal que podem comprometer a aquisicao da imunidade de grupo, constituindo, por isso, um importante problema de saude publica.

Suppressive effects of traditional herbal medicines on reversion of attenuated polio vaccine viruses to neurovirulent genotype

Suppressive effects of traditional herbal medicines on reversion of attenuated polio vaccine viruses to neurovirulent genotype

An increase in selenium intake improves immune function and poliovirus handling in adults with marginal selenium status

Dietary selenium intakes in many countries, including the United Kingdom, are lower than international recommendations. No functional consequences of these lower intakes have been recognized, although experimental studies suggest that they might contribute to reduced immune function, increased cancer incidence, and increased susceptibility to viral disease. The objective was to assess whether administration of small selenium supplements to otherwise healthy UK subjects leads to functional changes in immune status and the rates of clearance and mutation of a picornavirus: live attenuated polio vaccine. Twenty-two adult UK subjects with relatively low plasma selenium concentrations (<1.2 micromol/L, approximately 60% of those screened) received 50 or 100 microg Se (as sodium selenite) or placebo daily for 15 wk in a double-blind study. All subjects received an oral live attenuated poliomyelitis vaccine after 6 wk and enriched stable (74)Se intravenously 3 wk later. Selenium supplementation increased plasma selenium concentrations, the body exchangeable selenium pool (measured by using (74)Se), and lymphocyte phospholipid and cytosolic glutathione peroxidase activities. Selenium supplements augmented the cellular immune response through an increased production of interferon gamma and other cytokines, an earlier peak T cell proliferation, and an increase in T helper cells. Humoral immune responses were unaffected. Selenium-supplemented subjects also showed more rapid clearance of the poliovirus, and the poliovirus reverse transcriptase-polymerase chain reaction products recovered from the feces of the supplemented subjects contained a lower number of mutations. The data indicate that these subjects had a functional selenium deficit with suboptimal immune status and a deficit in viral handling. They also suggest that the additional 100 microg Se/d may be insufficient to support optimal function.

Live attenuated polio vaccine and the risk of intussusception

Aims Since suspicion has been raised that administration of an oral live attenuated rotavirus vaccine may increase the risk of intussusception in young children, there has been concern about the possible effects of oral polio vaccine. The aim of the study was to evaluate the relationship between oral attenuated polio vaccine and intussusception in children below the age of 1 year.Methods We conducted a nested case‐control analysis based on data from the General Practice Research Database which encompassed 133 children who developed documented intussusception during the first year of life and 515 controls.Results The time from oral polio vaccine to the index date was similar in cases and controls. Relative risk estimates for intussusception ranged from 0.7 (95% CI 0.2, 2.1) for babies whose last oral polio vaccine was given 29‐35 days before their index date to 1.0 (95% CI 0.4, 2.3) for those whose last oral polio vaccine was given 15‐21 days before their index date (compared with babies vaccinated more than 43 days before their index date).Conclusions There is no suggestion that oral polio vaccine increases the risk for intussusception.

Live attenuated polio vaccine and the risk of intussusception

Live attenuated polio vaccine and the risk of intussusception

Analysis of the accumulation of mutants in Sabin attenuated polio vaccine viruses passaged in Vero cells

To confirm the safety of oral poliomyelitis vaccine (OPV) cultured in Vero cells, the genetic stability of cultured polio vaccine viruses was analysed by MAPREC (mutant analysis by PCR and restriction enzyme cleavage). The rates of mutant accumulation of the viruses passaged in Vero cells under a low multiplicity of infection (MOI) condition (approximately 10 −3.5 CCID 50/cell; the same as under usual OPV production conditions) were higher than those passaged in secondary cultured monkey kidney cells. However, the rates of mutant accumulation were restrained when the viruses were cultured under a high MOI condition (approximately 10 −1.5 CCID 50/cell) in Vero cells. Furthermore, neurovirulence of the passaged viruses in pollovirus susceptible transgenic mice PVR-Tg21 was shown to correlate highly with the results of MAPREC. It is expected that our results will contribute to the large scale preparation of safe and effective OPV using Vero cells.

Safety and immunogenicity of two inactivated poliovirus vaccines in combination with an acellular pertussis vaccine and diphtheria and tetanus toxoids in seventeen- to nineteen-month-old infants

Objectives: To compare the safety and immunity of an acellular pertussis vaccine containing pertussis toxoid, filamentous hemagglutinin, 69 kd protein, fimbriae 2 and 3 combined with diphtheria and tetanus toxoids given as single or separate injection with inactivated poliovirus vaccine (MRC-5– or Vero cell–derived) or live attenuated polio vaccine. Methods: A total of 425 healthy children between 17 and 19 months of age who were receiving the fourth dose of their routine immunization series were randomly allocated to receive either the acellular pertussis vaccine and oral poliovirus vaccine or one of two inactivated poliovirus vaccines as a combined injection or separate injections. Results: Although minor adverse events were commonly reported, differences between the groups were few. Fever and decreased feeding were less common in recipients of live attenuated poliovirus vaccine than the combination vaccine containing MRC-5 cell–derived inactivated poliovirus vaccine. A significant antibody response was demonstrated in all groups against all the antigens contained in the vaccines. Antibodies against poliovirus were higher in the groups immunized with the inactivated poliovirus vaccine than the live attenuated vaccine. Anti–69 kd protein antibodies were higher in the group given the MRC-5 cell–derived inactivated poliovirus vaccine as a combined injection than in the group given the separate injection or the group immunized with the live attenuated poliovirus vaccine. Conclusion: The five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids is safe and immunogenic when combined with either MRC-5– or Vero cell– derived inactivated poliovirus vaccine. This will facilitate the implementation of acellular pertussis vaccine and the movement to inactivated poliovirus vaccine programs.

Point mutations involved in the attenuation/neurovirulence alternation in type 1 and 2 oral polio vaccine strains detected by site-specific polymerase chain reaction

One of the problems raised by the use of the attenuated oral poliovirus vaccine (OPV) Sabin strains is the genetic instability of the attenuated phenotype upon multiplication in vivo. Nucleotide sites critical for attenuation were identified for each of the three poliovirus serotypes. One important position lies in the 5' non-coding region of the genome of each of the three OPV strains, at nucleotide 480 in type 1, 481 in type 2 and 472 in type 3. Point mutations at these positions were usually selected upon multiplication in vivo as substitutions of the vaccine-type residue. The reversion was found to correlate with an increased degree of neurovirulence. To screen easily for this mutation in a great number of strains, we developed a site-specific polymerase chain reaction method based on the property of the Taq polymerase to elongate only primers with a perfect homology at the 3' extremity. We screened for this mutation in five type 1 and nine type 2 polio vaccine-derived strains isolated from vaccine-associated paralytic poliomyelitis (VAPP) cases and in 16 such strains isolated from healthy vaccinees. All 14 strains isolated from VAPP presented the reversion. Of the eight pairs of type 1 isolates from healthy vaccinees, four presented the reversion 3 days after vaccine administration and all but one at 7 days postvaccination. These results support the involvement of the 5' non-coding specific nucleotide sites in the reversion to neurovirulence of attenuated polio vaccine strains upon multiplication in the human gut.(ABSTRACT TRUNCATED AT 250 WORDS)

Shedding of Virulent Poliovirus Revertants during Immunization with Oral Poliovirus Vaccine after Prior Immunization with Inactivated Polio Vaccine

Fecal shedding of virulent revertant polioviruses was examined in isolates from infants previously immunized with > or = 1 dose of orally administered live attenuated polio vaccine (OPV) alone, enhanced-potency inactivated polio vaccine (EIPV) alone, or a combination of both. After administration of OPV alone, vaccine poliovirus serotypes were recovered in feces within 1 week and for as long as 31-60 days in 30%-80% of subjects after 1 or 2 doses and in 30%-50% after immunization with > or = 3 doses. No revertant poliovirus shedding was observed after OPV challenge in subjects immunized previously with > or = 3 doses of OPV. However, fecal shedding of revertant poliovirus after OPV challenge was observed in 50%-100% of subjects previously immunized with > or = 3 doses of the EIPV. These findings suggest that prior immunization with EIPV does not prevent fecal shedding of revertant polioviruses after subsequent reexposure to OPV.