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1.
Zhonghua Yu Fang Yi Xue Za Zhi ; 53(5): 513-518, 2019 May 06.
Artigo em Chinês | MEDLINE | ID: mdl-31091611

RESUMO

Objective: To evaluate the immunogenicity of different strains of inactivated poliomyelitis vaccines (IPV) by sequential program. Methods: This parallel-group controlled trial was conducted in immunization clinics in Shanghai from March 2016 to September 2017. Sabin strains inactivated poliomyelitis vaccines (sIPV), WPV strains inactivated poliomyelitis vaccines (wIPV) and live poliomyelitis Type Ⅰ Type Ⅲ vaccine (bOPV) as the investigational vaccine were used at 2, 3, 4 months old in 325 infants in Shanghai. Infants vaccinated by four sequential program were divided into 4 groups: sIPV+sIPV+bOPV, sIPV+wIPV+bOPV, wIPV+sIPV+bOPV and wIPV+wIPV+bOPV. A total of 230 investigators' blood samples were collected before primary immunization and 163 investigators' blood samples were collected after primary immunization. A total of 151 investigators (36, 44, 30 and 41 in each group) finished primary immunization and blood sampling before and after the primary immunization. The geometric mean titer (GMT) of poliovirus typesⅠ and Ⅲ neutralizing antibody was tested and calculated, and the positive results of antibody before and after primary immunization were analyzed. Results: Among the 151 investigators, the age were (2.27±0.61) months and birth weight were (3.27±0.43) kg, and 70 were male. The positive rates of typeⅠwas 98.68% (149 cases), and type Ⅲ was 97.35% (147 cases); the number of investigators tested in each group was 36, 44, 30 and 41, respectively; the positive rates of typeⅠwas 97.22% (35 cases), 100.00% (44 cases), 96.67% (29 cases) and 100.00% (41 cases) (P=0.345); the positive rates of type Ⅲ were 97.22% (35 cases), 95.45% (42 cases), 96.67% (29 cases) and 100.00% (41 cases) (P=0.614). Conclusion: Using sIPV and wIPV simultaneously or alternately for sequential immunization of poliomyelitis vaccines showed good immunogenicity for infants at appropriate age.


Assuntos
Poliomielite/imunologia , Vacina Antipólio de Vírus Inativado/imunologia , China , Feminino , Humanos , Esquemas de Imunização , Lactente , Masculino , Vacina Antipólio de Vírus Inativado/administração & dosagem
2.
Lancet ; 393(10191): 2624-2634, 2019 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-31104832

RESUMO

BACKGROUND: Intradermal administration of fractional inactivated poliovirus vaccine (fIPV) is a dose-sparing alternative to the intramuscular full dose. We aimed to compare the immunogenicity of two fIPV doses versus one IPV dose for routine immunisation, and also assessed the immunogenicity of an fIPV booster dose for an outbreak response. METHODS: We did an open-label, randomised, controlled, inequality, non-inferiority trial in two clinics in Dhaka, Bangladesh. Healthy infants were randomly assigned at 6 weeks to one of four groups: group A received IPV at age 14 weeks and IPV booster at age 22 weeks; group B received IPV at age 14 weeks and fIPV booster at age 22 weeks; group C received IPV at age 6 weeks and fIPV booster at age 22 weeks; and group D received fIPV at 6 weeks and 14 weeks and fIPV booster at age 22 weeks. IPV was administered by needle-syringe as an intramuscular full dose (0·5 mL), and fIPV was administered intradermally (0·1 mL of the IPV formulation was administered using the 0·1 mL HelmJect auto-disable syringe with a Helms intradermal adapter). Both IPV and fIPV were administered on the outer, upper right thigh of infants. The primary outcome was vaccine response to poliovirus types 1, 2, and 3 at age 22 weeks (routine immunisation) and age 26 weeks (outbreak response). Vaccine response was defined as seroconversion from seronegative (<1:8) at baseline to seropositive (≥1:8) or four-fold increase in reciprocal antibody titres adjusted for maternal antibody decay and was assessed in the modified intention-to-treat population (infants who received polio vaccines per group assignment and polio antibody titre results to serotypes 1, 2, and 3 at 6, 22, 23, and 26 weeks of age). The non-inferiority margin was 12·5%. This trial is registered with ClinicalTrials.gov, number NCT02847026. FINDINGS: Between Sept 1, 2016 and May 2, 2017, 1076 participants were randomly assigned and included in the modified intention-to-treat analysis: 271 in Group A, 267 in group B, 268 in group C, and 270 in group D. Vaccine response at 22 weeks to two doses of fIPV (group D) was significantly higher (p<0·0001) than to one dose of IPV (groups A and B) for all three poliovirus serotypes: the type 1 response comprised 212 (79% [95% CI 73-83]) versus 305 (57% [53-61]) participants, the type 2 response comprised 173 (64% [58-70]) versus 249 (46% [42-51]) participants, and the type 3 response comprised 196 (73% [67-78]) versus 196 (36% [33-41]) participants. At 26 weeks, the fIPV booster was non-inferior to IPV (group B vs group A) for serotype 1 (-1·12% [90% CI -2·18 to -0·06]), serotype 2 (0·40%, [-2·22 to 1·42]), and serotype 3 (1·51% [-3·23 to -0·21]). Of 129 adverse events, 21 were classified as serious including one death; none were attributed to IPV or fIPV. INTERPRETATION: fIPV appears to be an effective dose-sparing strategy for routine immunisation and outbreak responses. FUNDING: US Centers for Disease Control and Prevention.


Assuntos
Surtos de Doenças/prevenção & controle , Poliomielite/imunologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Poliovirus/imunologia , Anticorpos Antivirais/metabolismo , Bangladesh , Feminino , Humanos , Imunização Secundária , Lactente , Injeções Intramusculares/instrumentação , Masculino , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/imunologia
3.
PLoS One ; 14(4): e0215079, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31002702

RESUMO

INTRODUCTION: The prevalence of HIV infection in South African pregnant women has been approximately 30% over the past decade; however, there has been a steady decline in mother-to-child transmission of HIV from 8% in 2008 to <2% in 2015. We evaluated the immunogenicity of live-attenuated trivalent oral polio vaccine (OPV) following the primary vaccination series (doses at birth, 6, 10 and 14 weeks of age) in HIV-exposed uninfected (HEU), HIV-infected infants initiated on early anti-retroviral treatment (HIV+/ART+), HIV-infected infants on deferred ART (HIV+/ART-) and HIV-unexposed infants (HU) as the referent group. METHODS: Serum polio neutralization antibody titres were evaluated to serotype-1, serotype-2 and serotype-3 at 6, 10 and 18 weeks of age. Antibody titres ≥8 were considered seropositive and sero-protective. RESULTS: At 18 weeks of age, following the complete primary series of four OPV doses, no differences in GMTs, percentage of infants with sero-protective titres and median fold change in antibody titre (18 weeks vs 6 weeks) were observed in HEU infants (n = 114) and HIV+/ART+ infants (n = 162) compared to HU infants (n = 104) for the three polio serotypes. However, comparing HIV+/ART- infants (n = 70) to HU infants at 18 weeks of age, we observed significantly lower GMTs for serotype-1 (p = 0.022), serotype-2 (p<0.001) and serotype-3 (p<0.001), significantly lower percentages of infants with sero-protective titres for the three serotypes (p<0.001), and significantly lower median fold change in antibody titre for serotype-1 (p = 0.048), serotype-2 (p = 0.003) and serotype-3 (p = 0.008). CONCLUSION: Delaying initiation of ART in HIV-infected infants was associated with an attenuated immune response to OPV following a four-dose primary series of vaccines, whereas immune responses to OPV in HIV-infected children initiated on ART early in infancy and HEU children were similar to HU infants.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/transmissão , HIV/imunologia , Transmissão Vertical de Doença Infecciosa/estatística & dados numéricos , Poliomielite/imunologia , Vacinas contra Poliovirus/administração & dosagem , Poliovirus/imunologia , Anticorpos Antivirais/imunologia , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Poliomielite/epidemiologia , Poliomielite/prevenção & controle , Poliovirus/efeitos dos fármacos , Gravidez , África do Sul/epidemiologia , Vacinação
4.
Vaccine ; 37(2): 352-365, 2019 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-30442479

RESUMO

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. METHODS: Polio neutralizing antibody assays were conducted at 7 and 15 months of age for serotypes 1 and 3. Analyses were conducted on children receiving ≥3 OPV doses (n = 1449). History of vaccination, feeding patterns, physical growth, home environment, diarrhea, enteropathogen detection, and gut inflammation were examined as risk factors for non-response [Log2(titer) < 3] and Log2(titer) by serotype using multivariate regression. FINDINGS: Serotype 1 seroconversion was significantly higher than serotype 3 (96.6% vs. 89.6%, 15 months). Model results indicate serotypes 1 and 3 failure was minimized following four and six OPV doses, respectively; however, enteropathogen detection and poor socioeconomic conditions attenuated response in both serotypes. At three months of age, bacterial detection in stool reduced serotype 1 and 3 Log2 titers by 0.34 (95% CI 0.14-0.54) and 0.53 (95% CI 0.29-0.77), respectively, and increased odds of serotype 3 failure by 3.0 (95% CI 1.6-5.8). Our socioeconomic index, consisting of Water, Assets, Maternal education, and Income (WAMI), was associated with a 0.79 (95% CI 0.15-1.43) and 1.23 (95% CI 0.34-2.12) higher serotype 1 and 3 Log2 titer, respectively, and a 0.04 (95% CI 0.002-0.40) lower odds of serotype 3 failure. Introduction of solids, transferrin receptor, and underweight were differentially associated with serotype response. Other factors, including diarrheal frequency and breastfeeding practices, were not associated with OPV response. INTERPRETATION: Under real-world conditions, improved vaccination coverage and socio-environmental conditions, and reducing early life bacterial exposures are key to improving OPV response and should inform polio eradication strategies.


Assuntos
Erradicação de Doenças/métodos , Programas de Imunização , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/imunologia , Vacina Antipólio Oral/imunologia , Anticorpos Neutralizantes/sangue , Estudos de Coortes , Fezes/virologia , Feminino , Saúde Global , Humanos , Esquemas de Imunização , Lactente , Masculino , Testes de Neutralização , Poliomielite/imunologia , Poliovirus/imunologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio Oral/administração & dosagem , Sorogrupo , Cobertura Vacinal/métodos
7.
Clin Infect Dis ; 67(suppl_1): S78-S84, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376083

RESUMO

Background: Mutations associated with prolonged replication of the attenuated polioviruses found in oral poliovirus vaccine (OPV) can lead to vaccine-derived poliovirus (VDPV) and cause paralysis indistinguishable from that caused by wild poliovirus. In response, the World Health Organization has initiated the transition to exclusive use of inactivated poliovirus vaccine (IPV), with OPV administration in cases of outbreak. However, it is currently unclear how IPV-only vaccination, well known to provide humoral but not mucosal immunity, will impact the development of paralysis causing OPV variants. Children infected with human immunodeficiency virus (HIV) have been documented to show decreased mucosal immunity following OPV vaccination. Thus, HIV-infected children vaccinated with OPV may serve as proxy for children with IPV-only vaccination. Methods: We conducted a prospective study of Zimbabwean infants receiving OPV as part of their routine vaccination schedule. Stool samples collected from OPV-vaccinated children serially until age 24 months were tested for OPV serotypes using a real-time polymerase chain reaction protocol that quantifies the amount of mutant OPV variants found in each sample. Results: Out of 2130 stool samples collected from 402 infants 365 stool samples were OPV positive: 313 from 212 HIV-noninfected (HIV-) infants and 52 from 34 HIV-infected (HIV+) infants. HIV- infants showed significantly higher proportions of OPV mutants when compared to HIV+ infants. Conclusions: HIV infection is associated with a reduced proportion of OPV vaccine associated paralytic polio mutants. These results suggest that OPV administered to individuals previously vaccinated only with IPV will show decreased propensity for OPV mutations.


Assuntos
Infecções por HIV/complicações , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio Oral/administração & dosagem , Poliovirus/genética , Vacinação , Fezes/virologia , Humanos , Esquemas de Imunização , Lactente , Mutação Puntual , Poliomielite/imunologia , Poliomielite/virologia , Poliovirus/imunologia , Estudos Prospectivos , Sorogrupo , Eliminação de Partículas Virais , Organização Mundial da Saúde , Zimbábue
8.
Clin Infect Dis ; 67(suppl_1): S85-S89, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376085

RESUMO

Background: As wild poliovirus is eradicated and countries switch from oral poliovirus vaccine (OPV) to inactivated poliovirus vaccine (IPV) per World Health Organization recommendations, preventing circulation of vaccine-derived poliovirus (cVDPV) is a top priority. Currently, the impact of prior poliovirus vaccination on OPV shedding is not fully understood. Methods: Stool samples from 2 populations were tested for OPV to assess shedding patterns. 505 samples from 43 US children vaccinated with OPV were collected over 42 days post-vaccination. 1,379 samples from 148 Mexican children vaccinated with OPV were collected over 71 days post-vaccination. Prior vaccination history was recorded for both groups. Results: Seventeen (40%) of the US children had never received poliovirus vaccination while the Mexican children had received at least 2 doses of IPV and 116 (78%) had OPV exposure. In total, 84% of US children and 78% of Mexican children shed OPV (P = .44, Fisher exact test), with a mean shedding duration of 17.4 days for US children and 9.3 days for Mexican children (P < .0001, Wilcoxon-Mann Whitney test). Conclusions: Prior vaccination did not affect the likelihood of shedding, as the US and Mexico cohorts had similar shedding proportions. However, prior vaccination affected shedding duration as the Mexican children, who were largely OPV exposed and all of whom had at least 2 IPV vaccinations, shed OPV for half as long as the US cohort. Since different countries maintain different poliovirus vaccination schedules, it is likely that duration of shedding of OPV varies in populations around the world.


Assuntos
Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio Oral/administração & dosagem , Poliovirus/imunologia , Vacinação , Fezes/virologia , Humanos , Lactente , México , Poliomielite/imunologia , Poliomielite/virologia , Estados Unidos , Eliminação de Partículas Virais
9.
Clin Infect Dis ; 67(suppl_1): S51-S56, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376088

RESUMO

Background: Inactivated poliovirus vaccine (IPV) alone does not induce mucosal immunity. However, it was hypothesized that administration of IPV together with bivalent (types 1+3) oral poliovirus vaccine (bOPV) may stimulate mucosal cross-immunity to poliovirus type 2 (PV2). Methods: Cuban infants were randomized to receive either one dose of IPV (Arm A); one dose of IPV with bOPV (Arm B) at about 6 months of age or no vaccine (Arm C). Subjects were challenged with one dose of trivalent OPV (tOPV); they were about 7 months old in arms A and B, and about 3 months old in arm C at a time of the tOPV challenge. Sera were collected before vaccination and 30 days after tOPV challenge and tested for presence of poliovirus neutralizing antibodies; stool samples were collected at days 0, 7, 14, 21 and 49 post-challenge and tested for presence of poliovirus. Results: We enrolled 333 children. Excretion of PV2 following tOPV challenge was highest on day 7 (75 [CI 95% = 65-82%], 68 [CI 95% = 58-75%] and 73 [CI 95% = 63-80%] for study arms A, B, and C respectively); excretion decreased with every subsequent stool sampling; no significant differences either in proportion of PV2 excretion or in its duration were observed between study arms. Conclusions: There was no reduction in excretion of PV2 after tOPV challenge in children who had received IPV with bOPV when compared to those who had received IPV alone or no vaccine. Polio eradication program cannot assume any PV2 mucosal response with the current polio immunization schedule. Clinical Trials Registration: The trial was registered with the Australian New Zealand Clinical Trials Registry and allocated trial number ACTRN12616000169448.


Assuntos
Poliomielite/imunologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio Oral/administração & dosagem , Poliovirus/imunologia , Anticorpos Neutralizantes , Fezes/virologia , Feminino , Humanos , Imunidade nas Mucosas , Esquemas de Imunização , Lactente , Masculino , Poliomielite/prevenção & controle , Poliomielite/virologia , Eliminação de Partículas Virais
10.
Clin Infect Dis ; 67(suppl_1): S66-S77, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376091

RESUMO

Background: As a risk-mitigation strategy to minimize paralytic polio following withdrawal of Sabin type 2 from the oral poliovirus vaccine in April 2016, a single full dose or 2 fractional doses of inactivated poliovirus vaccine (IPV) are recommended. However, limited knowledge exists on long-term persistence of immune memory following 1- or 2-dose IPV schedules. Methods: We examined induction and maintenance of immune memory following single- vs 2-dose IPV schedules, either full-dose intramuscular or fractional-dose intradermal, in rhesus macaques. Humoral responses, bone marrow-homing antibody-secreting plasma cells, and blood-circulating/lymph node-homing memory B cells were examined longitudinally. Results: A single dose of IPV, either full or fractional, induced binding antibodies and memory B cells in all vaccinated macaques, despite failing to induce neutralizing antibodies (NT Abs) in many of them. However, these memory B cells declined rapidly, reaching below detection in the systemic circulation by 5 months; although a low frequency of memory B cells was detectable in draining lymph nodes of some, but not all, animals. By contrast, a 2-dose vaccination schedule, either full or fractional, efficiently induced NT Abs in all animals along with bone marrow-homing plasma cells and memory B cells. These memory B cells persisted in the systemic circulation for up to 16 months, the maximum duration tested after the second dose of vaccination. Conclusions: Two doses of IPV, regardless of whether fractional or full, are more effective than a single dose for inducing long-lasting memory B cells.


Assuntos
Anticorpos Neutralizantes/imunologia , Linfócitos B/imunologia , Esquemas de Imunização , Poliomielite/imunologia , Poliovirus/imunologia , Vacinação , Animais , Humanos , Macaca mulatta , Modelos Animais , Poliomielite/prevenção & controle , Poliomielite/virologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio Oral/administração & dosagem
11.
Clin Infect Dis ; 67(suppl_1): S98-S102, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376093

RESUMO

Background: Currently, the primary mechanism for poliovirus detection is acute flaccid paralysis (AFP) surveillance, with environmental sampling serving as a complement. However, as AFP cases drop, environmental surveillance will become increasingly critical for poliovirus detection. Mexico provides a natural environment to study oral polio vaccine (OPV) transmission, as it provides routine injected polio vaccine immunization and biannual OPV campaigns in February and May. Methods: As part of a study of OPV transmission in which 155 children were vaccinated with OPV, monthly sewage samples were collected from rivers leading from 3 indigenous Mexican villages (Capoluca, Campo Grande, and Tuxpanguillo) from February to May 2015. Samples were also collected from October 2015 to October 2017, during which time there were standard OPV campaigns. Samples were analyzed for the presence of OPV serotypes, using a real-time qualitative polymerase chain reaction assay capable of detecting as few as 9, 12, and 10 copies/100 µL of viral ribonucleic acid for OPV serotypes 1, 2, and 3 (OPV-1, -2, and -3), respectively. Included here are 54 samples, taken up to November 2016. Results: Of the 54 samples, 13 (24%) were positive for OPV. After the vaccination of 155 children in February 2015, OPV was found 2 months after vaccination. After unrestricted OPV administration in February 2016, OPV was detected in sewage up to 8 months after vaccination. OPV-3 was found in 11 of the 13 positive samples (85%), OPV-2 was found in 3 positive samples (23%), and OPV-1 was found in 1 sample (8%). Conclusions: OPV can be detected even when small amounts of the vaccine are introduced into a community, as shown by OPV-positive sewage samples even when only 155 children were vaccinated. When OPV vaccination was unrestricted, sewage samples were positive up to 8 months after vaccination, implying community OPV circulation for at least 8 months. OPV-3 was the serotype most found in these samples, indicating prolonged transmission of OPV-3 when compared to the other serotypes. Future work could compare the phylogenetic variance of OPV isolates from sewage after OPV vaccinations.


Assuntos
Monitoramento Ambiental , Reação em Cadeia da Polimerase Multiplex/métodos , Poliomielite/transmissão , Vacina Antipólio Oral , Poliovirus/isolamento & purificação , Vacinação , Humanos , México , Poliomielite/imunologia , Poliomielite/virologia , Poliovirus/genética , Poliovirus/imunologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Rios/virologia , Sensibilidade e Especificidade , Sorogrupo , Esgotos/virologia , Eliminação de Partículas Virais
12.
Clin Infect Dis ; 67(suppl_1): S57-S65, 2018 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-30376095

RESUMO

Background: Quantifying interference of maternal antibodies with immune responses to varying dose schedules of inactivated polio vaccine (IPV) is important for the polio endgame as IPV replaces oral polio vaccine (OPV). Methods: Type 2 poliovirus humoral and intestinal responses were analyzed using pre-IPV type 2 seropositivity as proxy for maternal antibodies from 2 trials in Latin America. Infants received 1 or 2 doses of IPV in sequential IPV-bivalent oral polio vaccine (bOPV) or mixed bOPV-IPV schedules. Results: Among infants vaccinated with bOPV at age 6, 10, and 14 weeks of age and IPV at 14 weeks, those with type 2 pre-IPV seropositivity had lower seroprotection rates than seronegative infants at 4 weeks (92.7% vs 83.8%; difference, 8.9% [95% confidence interval, 0.6%-19.9%]; n = 260) and 22 weeks (82.7% vs 60.4%; difference, 22.3 [12.8%-32.4%]; n = 481) post-IPV. A second IPV at age 36 weeks resulted in 100% seroprotection in both groups. Among infants vaccinated with 1 IPV at age 8 weeks followed by 2 doses of bOPV, pre-IPV type 2-seropositive infants had lower seroprotection at age 28 weeks than those who were seronegative (93.0% vs 73.9%; difference, 19.6% [95% confidence interval, 7.3%-29.4%]; n = 168). A second dose of IPV at 16 weeks achieved >97% seroprotection at age 24 or 28 weeks, regardless of pre-IPV status. Poliovirus shedding after challenge with monovalent OPV, serotype 2, was higher in pre-IPV seropositive infants given sequential IPV-bOPV. No differences were observed in the mixed bOPV-IPV schedule. Conclusions: The presence of maternal antibody is associated with lower type 2 post-IPV seroprotection rates among infants who receive a single dose of IPV. This impact persists until late in infancy and is overcome by a second IPV dose.


Assuntos
Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio Oral/administração & dosagem , Poliovirus/imunologia , Vacinação , Feminino , Humanos , Lactente , Intestinos/imunologia , América Latina , Poliomielite/imunologia , Poliomielite/virologia , Estudos Soroepidemiológicos , Sorogrupo
13.
BMC Res Notes ; 11(1): 717, 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30305145

RESUMO

OBJECTIVE: Primary immunodeficiency (PID) patients are prone to developing viral infections and should not be vaccinated with live vaccines. In such patients, prolonged excretion and viral divergence may occur and they may subsequently act as reservoirs in the community introducing mutated virus and jeopardizing polio eradication. One hundred and thirty PID cases were included for poliovirus detection in stool with assessment of divergence of detected polioviruses from oral polio vaccine (OPV) virus. Clinical presentations of PID patients with detectable poliovirus in stool specimens are described. RESULTS: Six PID patients (4.5%) had detectable vaccine-derived poliovirus (VDPV) excretion in stool specimens; of these, five patients had severe combined immunodeficiency (two with acute flaccid paralysis, one with meningoencephalitis and two without neurological manifestations), and one patient had X-linked agammaglobulinemia (paralysis developed shortly after diagnosis of immunodeficiency). All six case-patients received trivalent OPV. Five case-patients had type 2 immunodeficiency-related vaccine-derived polioviruses (iVDPV2) excretion; one had concomitant excretion of Sabin like type 3 virus and one was identified as iVDPV1 excretor. Surveillance for poliovirus excretion among PID patients is critical as these patients represent a potential source to reseed polioviruses into populations.


Assuntos
Portador Sadio/virologia , Síndromes de Imunodeficiência/virologia , Poliomielite/transmissão , Vacina Antipólio Oral/efeitos adversos , Vacinação/efeitos adversos , Eliminação de Partículas Virais , Portador Sadio/imunologia , Portador Sadio/patologia , Erradicação de Doenças , Egito/epidemiologia , Fezes/virologia , Feminino , Humanos , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/mortalidade , Lactente , Masculino , Poliomielite/epidemiologia , Poliomielite/imunologia , Poliomielite/prevenção & controle , Poliovirus/imunologia , Poliovirus/patogenicidade , Vacina Antipólio Oral/administração & dosagem , Vigilância em Saúde Pública
14.
Vaccine ; 36(45): 6782-6789, 2018 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-30249424

RESUMO

BACKGROUND: In order to completely eradicate polio caused by wild poliovirus infection as well as vaccine-associated paralytic polio (VAPP), Sabin inactivated poliovirus vaccine (sIPV) should be developed to meet the requirements for biosafety and affordable strategy in the developing countries. METHOD: A randomized, double-blinded clinical trial was conducted to compare the immunogenicity and safety among infants aged 2 months (60-90 days) receiving five different vaccination regimens: the test groups (A, B, and C) received three doses of sIPV with high, medium, and low D antigen content, respectively, on the month 0, 1, 2 schedule; two control groups (D and E) received three doses of conventional IPV (cIPV) or sIPV (CAMS), respectively, on the same schedule as that of test groups. Serum samples were collected immediately before the 1st dose and 30 days after the 3rd dose vaccination to assess the immunogenicity. Adverse events occurring within 30 days after each dose were collected to assess the safety. RESULTS: After three doses, seroconversion rates in groups A-E were 100%, 98.2%, 100%, 100%, and 100%, respectively, for type 1; 99.1%, 100%, 98.1%, 100%, and 97.1%, respectively, for type 2; and 100%, 100%, 100%, 100%, and 99.0%, respectively, for type 3. The seropositive rates (≥1:8) of groups A-E for all types were nearly 100%. The GMTs in the target dose group (group B) were 4635, 342, and 2218 for type 1-3, respectively. The most common injection-site and systemic adverse reactions were swelling and fever respectively. The swelling (4.2%, P = 0.0075) and fever (58.3%, P = 0.0188) frequency of group A were statistically significantly higher than any other groups. CONCLUSION: The test sIPV generally demonstrated good safety and immunogenicity. The medium-D antigen dose would be a preferred choice for the further phase III clinical trial in consideration of its high immunogenicity for all serotypes and the satisfying tolerance. CLINICAL TRIALS REGISTRATION: NCT02985320.


Assuntos
Vacina Antipólio de Vírus Inativado/efeitos adversos , Vacina Antipólio de Vírus Inativado/imunologia , Vacina Antipólio Oral/efeitos adversos , Vacina Antipólio Oral/imunologia , Feminino , Humanos , Lactente , Poliomielite/imunologia , Poliomielite/prevenção & controle , Poliovirus/imunologia
15.
Front Immunol ; 9: 1826, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30147693

RESUMO

Background: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by Bruton's tyrosine kinase (BTK) mutation. Patients are susceptible to severe enterovirus infections. The underlying mechanism remains unknown. BTK is involved in toll-like receptors pathway, which initiates antiviral responses including interferon (IFN) productions. Objective: To demonstrate type I and III IFN productions in dendritic cells of XLA patients is decreased in response to oral poliovirus vaccine (OPV) but not H1N1 virus. Methods: Monocyte-derived dendritic cells (MoDCs) were derived from nine XLA patients aged 22-32 years old and 23 buffy coats from Hong Kong Red Cross blood donors. LFM-A13 was used to inhibit BTK. OPV Sabin type 1 and H1N1 influenza virus were used to stimulate MoDCs with RPMI as mock stimulation. The antiviral cytokine productions and phenotypic maturation of MoDCs were determined 24 h post-stimulation. OPV RNA was determined at 0, 6, 12, and 24 h post-stimulation. Results: Upon OPV stimulation, IFN-α2, IFN-ß, and IFN-λ1 productions in MoDCs from XLA patients and BTK-inhibited MoDCs of healthy controls were significantly lower than that from healthy controls. Whereas upon H1N1 stimulation, the IFN-α2, IFN-ß, and IFN-λ1 productions were similar in MoDCs from XLA patients, BTK-inhibited MoDCs of healthy controls and healthy controls. The mean fluorescent intensities (MFI) of CD83, CD86, and MHC-II in MoDCs from XLA patients in response to OPV was similar to that in response to mock stimulation, while the MFI of CD83, CD86, and MHC-II were significantly higher in response to H1N1 stimulation than that in response to mock stimulation. Whereas, the MFI of CD83, CD86, and MHC-II in MoDCs of healthy controls were significantly higher in response to both OPV and H1N1 stimulation compared to that in response to mock stimulation. Conclusion: Production of type I and III IFN in response to OPV was deficient in MoDCs from XLA patients, but was normal in response to H1N1 due to deficient BTK function. Moreover, phenotypic maturation of MoDCs from XLA patients was impaired in response to OPV but not to H1N1. These selective impairments may account for the unique susceptibility of XLA patients toward severe enterovirus infections.


Assuntos
Tirosina Quinase da Agamaglobulinemia/genética , Células Dendríticas/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Interferon Tipo I/metabolismo , Interferons/metabolismo , Poliomielite/imunologia , Poliovirus/imunologia , Adulto , Agamaglobulinemia , Diferenciação Celular , Células Cultivadas , Regulação da Expressão Gênica , Doenças Genéticas Ligadas ao Cromossomo X , Humanos , Mutação/genética , Transdução de Sinais , Receptores Toll-Like/metabolismo , Adulto Jovem
16.
Hum Vaccin Immunother ; 14(11): 2644-2648, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30059644

RESUMO

A cross-sectional study for poliovirus seroprevalence in Guangdong was carried out in 2014, just before a change in polio vaccine commenced in 2015. The aim of the study was to test whether polio immunity level was high enough to satisfy the polio vaccine switch. A total of 6339 people were tested for poliovirus neutralization antibodies (NA). Overall NA seropositivity for PV1, PV2 and PV3 were 95.2%, 94.9% and 88.7%, and the respective geometric mean titer (GMT) were 82.9, 55.8, and 26.3, respectively. There were statistically significant differences in the positive rates and GMT of the 3 serotypes and PV3 had relatively lower positive rates and GMT. The highest seropositivity and GMT were observed in the 1-9 year-old age group. The positive rates of NA and GMT for PV1, PV2 and PV3 in the western region of Guangdong were lower than those of other three regions. The results of this study showed that the population of Guangdong province had a high polio immunity level, a stable base for a polio vaccine switch.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Poliomielite/epidemiologia , Poliovirus/imunologia , Adolescente , Adulto , Distribuição por Idade , Criança , Pré-Escolar , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Imunogenicidade da Vacina , Lactente , Recém-Nascido , Masculino , Poliomielite/sangue , Poliomielite/imunologia , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/imunologia , Vacina Antipólio Oral/administração & dosagem , Vacina Antipólio Oral/imunologia , Estudos Soroepidemiológicos , Sorogrupo , Adulto Jovem
17.
Vaccine ; 36(32 Pt B): 4935-4938, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-29980387

RESUMO

BACKGROUND: To attain high coverage during polio vaccination campaigns, an outreach house-to-house strategy is used to administer oral poliovirus vaccine. Administering an injectable vaccine house-to-house requires a skilled work force and increases risks of needle stick injuries. Needle-free injection devices provide a safer alternative to needles and syringes for administering injectable vaccines. We evaluated the feasibility and acceptability of a needle-free injection device to administer injectable poliovirus vaccine during a house-to-house vaccination outreach activity. METHODS: Vaccination teams administered injectable poliovirus vaccine using the Pharmajet® needle-free intramuscular jet injector to children ages 6-59 months in 766 homes. Data on the feasibility of using the jet injector in an outreach campaign setting and the acceptability of the jet injector by caregivers and vaccinators were collected. RESULTS: A total of 993 injections were administered. Vaccinators faced challenges during device preparation in 16% (n = 158) of injections; challenges were related to problems loading the injector and not having a flat surface to use for setup of the injector. Among 32 vaccinators interviewed after the vaccination campaign, the main reported advantage of the device was absence of sharps disposal (91%) while the main reported disadvantage was unacceptability by parents (90%) which was related to the vaccine, not the device. CONCLUSIONS: The needle-free jet injector was feasible for use in house-to-house campaigns. Acceptability by vaccinators was low as 81% stated that the jet injector was not easier to use than needle and syringe. Parental refusal related to frequent polio vaccination campaigns was the biggest challenge. In addition, novelty of the device posed a challenge to teams as they needed to reassure parents about safety of the device. To take full advantage of the ability to take injectable vaccines door-to-door during vaccination campaigns using a needle-free jet injector device, tailored social mobilization efforts are needed ahead of campaigns.


Assuntos
Injeções a Jato/métodos , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/uso terapêutico , Poliovirus/patogenicidade , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Poliomielite/imunologia , Poliovirus/imunologia
18.
J Infect Dis ; 218(12): 1876-1882, 2018 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-29982532

RESUMO

Background: Inactivated poliovirus vaccine (IPV) boosts mucosal immunity in persons previously vaccinated with oral poliovirus vaccine (OPV). We assessed whether fractional-dose IPV (fIPV, 1/5th of full dose) administered intradermally also boosts mucosal immunity. Methods: Children 10-12 years old were enrolled in Sri Lanka and randomized to receive one dose IPV, fIPV, or no IPV vaccine. One month later, they received OPV challenge. Blood was collected at enrolment and before challenge; stool was collected at 3, 7, and 14 days post-challenge. Sera were analysed for presence of poliovirus neutralizing antibodies; stool was analysed for poliovirus. Results: We analysed 304/309 (98%) enrolled subjects. There were 16/97 (16%), 9/99 (9%), and 72/95 (76%) subjects excreting poliovirus after challenge in the IPV, fIPV and "No IPV Vaccine" study arms, respectively (P < .001 for comparison of IPV [or fIPV] vs "No IPV Vaccine"; P = .1 for comparisons of fIPV vs IPV). Relative decrease in excretion prevalence was 80% and 88% to IPV and fIPV, respectively, compared with the "No IPV Vaccine" control arm. Conclusions: Single fIPV dose boosted mucosal immunity to a similar degree as single full dose of IPV. This finding provides further evidence in support of fIPV for poliovirus outbreak response at the time of IPV global supply shortage. Clinical trials registration: Australia New Zealand Clinical Trial Registry ACTRN12616000124437p.


Assuntos
Imunidade nas Mucosas , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/imunologia , Administração Oral , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Criança , Fezes/virologia , Feminino , Humanos , Esquemas de Imunização , Masculino , Poliomielite/epidemiologia , Poliomielite/imunologia , Poliovirus/fisiologia , Sri Lanka/epidemiologia , Eliminação de Partículas Virais
20.
J Virol ; 92(17)2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29925653

RESUMO

The poliovirus eradication initiative has spawned global immunization infrastructure and dramatically decreased the prevalence of the disease, yet the original virus eradication goal has not been met. The suboptimal properties of the existing vaccines are among the major reasons why the program has repeatedly missed eradication deadlines. Oral live poliovirus vaccine (OPV), while affordable and effective, occasionally causes the disease in the primary recipients, and the attenuated viruses rapidly regain virulence and can cause poliomyelitis outbreaks. Inactivated poliovirus vaccine (IPV) is safe but expensive and does not induce the mucosal immunity necessary to interrupt virus transmission. While the need for a better vaccine is widely recognized, current efforts are focused largely on improvements to the OPV or IPV, which are still beset by the fundamental drawbacks of the original products. Here we demonstrate a different design of an antipoliovirus vaccine based on in situ production of virus-like particles (VLPs). The poliovirus capsid protein precursor, together with a protease required for its processing, are expressed from a Newcastle disease virus (NDV) vector, a negative-strand RNA virus with mucosal tropism. In this system, poliovirus VLPs are produced in the cells of vaccine recipients and are presented to their immune systems in the context of active replication of NDV, which serves as a natural adjuvant. Intranasal administration of the vectored vaccine to guinea pigs induced strong neutralizing systemic and mucosal antibody responses. Thus, the vectored poliovirus vaccine combines the affordability and efficiency of a live vaccine with absolute safety, since no full-length poliovirus genome is present at any stage of the vaccine life cycle.IMPORTANCE A new, safe, and effective vaccine against poliovirus is urgently needed not only to complete the eradication of the virus but also to be used in the future to prevent possible virus reemergence in a postpolio world. Currently, new formulations of the oral vaccine, as well as improvements to the inactivated vaccine, are being explored. In this study, we designed a viral vector with mucosal tropism that expresses poliovirus capsid proteins. Thus, poliovirus VLPs are produced in vivo, in the cells of a vaccine recipient, and are presented to the immune system in the context of vector virus replication, stimulating the development of systemic and mucosal immune responses. Such an approach allows the development of an affordable and safe vaccine that does not rely on the full-length poliovirus genome at any stage.


Assuntos
Vetores Genéticos , Vírus da Doença de Newcastle/genética , Poliomielite/prevenção & controle , Vacinas contra Poliovirus/imunologia , Poliovirus/genética , Vacinas de Partículas Semelhantes a Vírus/imunologia , Animais , Anticorpos Antivirais/sangue , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/imunologia , Cobaias , Imunidade nas Mucosas , Imunoglobulina A/imunologia , Imunoglobulina G/imunologia , Vírus da Doença de Newcastle/imunologia , Vírus da Doença de Newcastle/fisiologia , Poliomielite/imunologia , Poliomielite/virologia , Poliovirus/enzimologia , Poliovirus/imunologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/efeitos adversos , Vacina Antipólio de Vírus Inativado/genética , Vacina Antipólio de Vírus Inativado/imunologia , Vacinas contra Poliovirus/efeitos adversos , Vacinas contra Poliovirus/normas , Vacinação , Vacinas Vivas não Atenuadas/administração & dosagem , Vacinas Vivas não Atenuadas/efeitos adversos , Vacinas Vivas não Atenuadas/genética , Vacinas Vivas não Atenuadas/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/efeitos adversos , Vacinas de Partículas Semelhantes a Vírus/genética
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