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1.
Nat Commun ; 10(1): 5677, 2019 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831806

RESUMO

An important goal of the Zika virus (ZIKV) vaccine is to prevent a congenital syndrome in fetuses of pregnant women, but studies directly evaluating maternal vaccination for ZIKV are lacking. Here we report maternal vaccination using a live-attenuated ZIKV vaccine (3'UTR-∆10-LAV) in a pregnant mouse model. Maternal immunization with 3'UTR-∆10-LAV does not cause any adverse effects on pregnancy, fetal development, or offspring behavior. One maternal immunization fully protects dams against ZIKV infection and in utero transmission. Although neutralizing antibody alone is sufficient to prevent in utero transmission, a higher neutralizing titer is required to protect pregnant mice against in utero transmission than that required to protect non-pregnant mice against viral infection. The immunized dams transfer maternal antibodies to pups, which protect neonates against ZIKV infection. Notably, pregnancy weakens maternal T cell response to 3'UTR-∆10-LAV vaccination. Our results suggest that, besides vaccinating non-pregnant individuals, 3'UTR-∆10-LAV may also be considered for maternal vaccination.


Assuntos
Imunidade , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Vacinação , Vacinas Virais/imunologia , Infecção por Zika virus/prevenção & controle , Zika virus/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Gravidez , Linfócitos T/imunologia , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêutico , Vacinas Virais/efeitos adversos , Vacinas Virais/uso terapêutico , Zika virus/genética , Infecção por Zika virus/virologia
2.
PLoS One ; 14(12): e0227109, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31881064

RESUMO

Staphylococcus aureus is known to produce persistent and chronic infections in both humans and animals. It is recognized that small-colony variants (SCVs), which produce higher levels of biofilm and that are capable of intracellular persistence, contribute to the chronicity or recurrence of infections and that this phenotype is inherent to the pathogenesis process. Prevention of S. aureus infections through vaccination has not yet met with considerable success. Some of the current vaccine formulations for S. aureus bovine mastitis consist of inactivated S. aureus bacteria, sometimes combined to E. coli J5. As such, the stimulation of cell-mediated immunity by these vaccines might not be optimal. With this in mind, we recently engineered a genetically stable double mutant SCV (ΔvraGΔhemB), which was highly attenuated in a mastitis model of infection. The present work describes the immune responses elicited in mice by various experimental vaccine compositions including the live-attenuated SCV double mutant and its inactivated form, combined or not with inactivated E. coli J5. The live-attenuated SCV was found to provoke a strong and balanced humoral response in immunized mice, as well as strong proliferation of ex-vivo stimulated splenocytes isolated from these animals. These splenocytes were also found to release high concentration of IL-17 and IFN-γ when compared to every other vaccination formulation. Inversely, the inactivated whole-cell vaccine, alone or in combination with the E. coli J5 bacterin, elicited lower antibody titers and failed to induce Th1 or Th17 cell-mediated responses in the splenocyte proliferation assay. Our results suggest that live-attenuated SCVs can trigger host immunity differently than inactivated bacteria and could represent a suitable vector for inducing strong humoral and cell-mediated immune responses, which are crucial for protection. This could represent an important improvement over existing vaccine formulations for preventing S. aureus bovine mastitis and other infections caused by this pathogen.


Assuntos
Imunidade Celular , Imunidade Humoral , Infecções Estafilocócicas/prevenção & controle , Vacinas Antiestafilocócicas/uso terapêutico , Staphylococcus aureus/imunologia , Vacinas Atenuadas/uso terapêutico , Animais , Células Cultivadas , Feminino , Camundongos , Infecções Estafilocócicas/imunologia , Vacinas Antiestafilocócicas/farmacologia , Vacinação , Vacinas Atenuadas/farmacologia
3.
Cochrane Database Syst Rev ; 2019(10)2019 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-31684685

RESUMO

BACKGROUND: Rotavirus results in more diarrhoea-related deaths in children under five years than any other single agent in countries with high childhood mortality. It is also a common cause of diarrhoea-related hospital admissions in countries with low childhood mortality. Rotavirus vaccines that have been prequalified by the World Health Organization (WHO) include a monovalent vaccine (RV1; Rotarix, GlaxoSmithKline), a pentavalent vaccine (RV5; RotaTeq, Merck), and, more recently, another monovalent vaccine (Rotavac, Bharat Biotech). OBJECTIVES: To evaluate rotavirus vaccines prequalified by the WHO (RV1, RV5, and Rotavac) for their efficacy and safety in children. SEARCH METHODS: On 4 April 2018 we searched MEDLINE (via PubMed), the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in the Cochrane Library), Embase, LILACS, and BIOSIS. We also searched the WHO ICTRP, ClinicalTrials.gov, clinical trial reports from manufacturers' websites, and reference lists of included studies and relevant systematic reviews. SELECTION CRITERIA: We selected randomized controlled trials (RCTs) in children comparing rotavirus vaccines prequalified for use by the WHO versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and assessed risks of bias. One review author extracted data and a second author cross-checked them. We combined dichotomous data using the risk ratio (RR) and 95% confidence interval (CI). We stratified the analysis by country mortality rate and used GRADE to evaluate evidence certainty. MAIN RESULTS: Fifty-five trials met the inclusion criteria and enrolled a total of 216,480 participants. Thirty-six trials (119,114 participants) assessed RV1, 15 trials (88,934 participants) RV5, and four trials (8432 participants) Rotavac. RV1 Children vaccinated and followed up the first year of life In low-mortality countries, RV1 prevents 84% of severe rotavirus diarrhoea cases (RR 0.16, 95% CI 0.09 to 0.26; 43,779 participants, 7 trials; high-certainty evidence), and probably prevents 41% of cases of severe all-cause diarrhoea (RR 0.59, 95% CI 0.47 to 0.74; 28,051 participants, 3 trials; moderate-certainty evidence). In high-mortality countries, RV1 prevents 63% of severe rotavirus diarrhoea cases (RR 0.37, 95% CI 0.23 to 0.60; 6114 participants, 3 trials; high-certainty evidence), and 27% of severe all-cause diarrhoea cases (RR 0.73, 95% CI 0.56 to 0.95; 5639 participants, 2 trials; high-certainty evidence). Children vaccinated and followed up for two years In low-mortality countries, RV1 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.14 to 0.23; 36,002 participants, 9 trials; high-certainty evidence), and probably prevents 37% of severe all-cause diarrhoea episodes (rate ratio 0.63, 95% CI 0.56 to 0.71; 39,091 participants, 2 trials; moderate-certainty evidence). In high-mortality countries RV1 probably prevents 35% of severe rotavirus diarrhoea cases (RR 0.65, 95% CI 0.51 to 0.83; 13,768 participants, 2 trials; high-certainty evidence), and 17% of severe all-cause diarrhoea cases (RR 0.83, 95% CI 0.72 to 0.96; 2764 participants, 1 trial; moderate-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.88 95% CI 0.83 to 0.93; high-certainty evidence). There were 30 cases of intussusception reported in 53,032 children after RV1 vaccination and 28 cases in 44,214 children after placebo or no intervention (RR 0.70, 95% CI 0.46 to 1.05; low-certainty evidence). RV5 Children vaccinated and followed up the first year of life In low-mortality countries, RV5 probably prevents 92% of severe rotavirus diarrhoea cases (RR 0.08, 95% CI 0.03 to 0.22; 4132 participants, 5 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 57% of severe rotavirus diarrhoea (RR 0.43, 95% CI 0.29 to 0.62; 5916 participants, 2 trials; high-certainty evidence), but there is probably little or no difference between vaccine and placebo for severe all-cause diarrhoea (RR 0.80, 95% CI 0.58 to 1.11; 1 trial, 4085 participants; moderate-certainty evidence). Children vaccinated and followed up for two years In low-mortality countries, RV5 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.08 to 0.39; 7318 participants, 4 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 41% of severe rotavirus diarrhoea cases (RR 0.59, 95% CI 0.43 to 0.82; 5885 participants, 2 trials; high-certainty evidence), and 15% of severe all-cause diarrhoea cases (RR 0.85, 95% CI 0.75 to 0.98; 5977 participants, 2 trials; high-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.86 to 1.01; moderate to high-certainty evidence). There were 16 cases of intussusception in 43,629 children after RV5 vaccination and 20 cases in 41,866 children after placebo (RR 0.77, 95% CI 0.41 to 1.45; low-certainty evidence). Rotavac Children vaccinated and followed up the first year of life Rotavac has not been assessed in any RCT in countries with low child mortality. In India, a high-mortality country, Rotavac probably prevents 57% of severe rotavirus diarrhoea cases (RR 0.43, 95% CI 0.30 to 0.60; 6799 participants, moderate-certainty evidence); the trial did not report on severe all-cause diarrhoea at one-year follow-up. Children vaccinated and followed up for two years Rotavac probably prevents 54% of severe rotavirus diarrhoea cases in India (RR 0.46, 95% CI 0.35 to 0.60; 6541 participants, 1 trial; moderate-certainty evidence), and 16% of severe all-cause diarrhoea cases (RR 0.84, 95% CI 0.71 to 0.98; 6799 participants, 1 trial; moderate-certainty evidence). No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.85 to 1.02; moderate-certainty evidence). There were eight cases of intussusception in 5764 children after Rotavac vaccination and three cases in 2818 children after placebo (RR 1.33, 95% CI 0.35 to 5.02; very low-certainty evidence). There was insufficient evidence of an effect on mortality from any rotavirus vaccine (198,381 participants, 44 trials; low- to very low-certainty evidence), as the trials were not powered to detect an effect at this endpoint. AUTHORS' CONCLUSIONS: RV1, RV5, and Rotavac prevent episodes of rotavirus diarrhoea. Whilst the relative effect estimate is smaller in high-mortality than in low-mortality countries, there is a greater number of episodes prevented in these settings as the baseline risk is much higher. We found no increased risk of serious adverse events. 21 October 2019 Up to date All studies incorporated from most recent search All published trials found in the last search (4 Apr, 2018) were included and 15 ongoing studies are currently awaiting completion (see 'Characteristics of ongoing studies').


Assuntos
Diarreia/prevenção & controle , Diarreia/virologia , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/administração & dosagem , Rotavirus/imunologia , Adulto , Criança , Pré-Escolar , Diarreia Infantil/prevenção & controle , Diarreia Infantil/virologia , Humanos , Lactente , Recém-Nascido , Ensaios Clínicos Controlados Aleatórios como Assunto , Vacinas contra Rotavirus/uso terapêutico , Vacinação , Vacinas Atenuadas/uso terapêutico , Adulto Jovem
4.
Cochrane Database Syst Rev ; 2019(11)2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31696946

RESUMO

BACKGROUND: Herpes zoster, commonly known as shingles, is a neurocutaneous disease caused by the reactivation of the virus that causes varicella (chickenpox). After resolution of the varicella episode, the virus can remain latent in the sensitive dorsal ganglia of the spine. Years later, with declining immunity, the varicella zoster virus (VZV) can reactivate and cause herpes zoster, an extremely painful condition that can last many weeks or months and significantly compromise the quality of life of the affected person. The natural process of aging is associated with a reduction in cellular immunity, and this predisposes older people to herpes zoster. Vaccination with an attenuated form of the VZV activates specific T-cell production avoiding viral reactivation. The USA Food and Drug Administration has approved a herpes zoster vaccine with an attenuated active virus, live zoster vaccine (LZV), for clinical use amongst older adults, which has been tested in large populations. A new adjuvanted recombinant VZV subunit zoster vaccine, recombinant zoster vaccine (RZV), has also been approved. It consists of recombinant VZV glycoprotein E and a liposome-based AS01B adjuvant system. This is an update of a Cochrane Review last updated in 2016. OBJECTIVES: To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. SEARCH METHODS: For this 2019 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 1, January 2019), MEDLINE (1948 to January 2019), Embase (2010 to January 2019), CINAHL (1981 to January 2019), LILACS (1982 to January 2019), WHO ICTRP (on 31 January 2019) and ClinicalTrials.gov (on 31 January 2019). SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine (any dose and potency) versus any other type of intervention (e.g. varicella vaccine, antiviral medication), placebo, or no intervention (no vaccine). Outcomes were incidence of herpes zoster, adverse events (death, serious adverse events, systemic reactions, or local reaction occurring at any time after vaccination), and dropouts. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 11 new studies involving 18,615 participants in this update. The review now includes a total of 24 studies involving 88,531 participants. Only three studies assessed the incidence of herpes zoster in groups that received vaccines versus placebo. Most studies were conducted in high-income countries in Europe and North America and included healthy Caucasians (understood to be white participants) aged 60 years or over with no immunosuppressive comorbidities. Two studies were conducted in Japan. Fifteen studies used LZV. Nine studies tested an RZV. The overall quality of the evidence was moderate. Most data for the primary outcome (incidence of herpes zoster) and secondary outcomes (adverse events and dropouts) came from studies that had a low risk of bias and included a large number of participants. The incidence of herpes zoster at up to three years follow-up was lower in participants who received the LZV (one dose subcutaneously) than in those who received placebo (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.43 to 0.56; risk difference (RD) 2%; number needed to treat for an additional beneficial outcome (NNTB) 50; moderate-quality evidence) in the largest study, which included 38,546 participants. There were no differences between the vaccinated and placebo groups for serious adverse events (RR 1.08, 95% CI 0.95 to 1.21) or deaths (RR 1.01, 95% CI 0.92 to 1.11; moderate-quality evidence). The vaccinated group had a higher incidence of one or more adverse events (RR 1.71, 95% CI 1.38 to 2.11; RD 23%; number needed to treat for an additional harmful outcome (NNTH) 4.3) and injection site adverse events (RR 3.73, 95% CI 1.93 to 7.21; RD 28%; NNTH 3.6) of mild to moderate intensity (moderate-quality evidence). These data came from four studies with 6980 participants aged 60 years or over. Two studies (29,311 participants for safety evaluation and 22,022 participants for efficacy evaluation) compared RZV (two doses intramuscularly, two months apart) versus placebo. Participants who received the new vaccine had a lower incidence of herpes zoster at 3.2 years follow-up (RR 0.08, 95% CI 0.03 to 0.23; RD 3%; NNTB 33; moderate-quality evidence). There were no differences between the vaccinated and placebo groups in incidence of serious adverse events (RR 0.97, 95% CI 0.91 to 1.03) or deaths (RR 0.94, 95% CI 0.84 to 1.04; moderate-quality evidence). The vaccinated group had a higher incidence of adverse events, any systemic symptom (RR 2.23, 95% CI 2.12 to 2.34; RD 33%; NNTH 3.0), and any local symptom (RR 6.89, 95% CI 6.37 to 7.45; RD 67%; NNTH 1.5). Although most participants reported that there symptoms were of mild to moderate intensity, the risk of dropouts (participants not returning for the second dose, two months after the first dose) was higher in the vaccine group than in the placebo group (RR 1.25, 95% CI 1.13 to 1.39; RD 1%; NNTH 100, moderate-quality evidence). Only one study reported funding from a non-commercial source (a university research foundation). All of the other included studies received funding from pharmaceutical companies. We did not conduct subgroup and sensitivity analyses AUTHORS' CONCLUSIONS: LZV and RZV are effective in preventing herpes zoster disease for up to three years (the main studies did not follow participants for more than three years). To date, there are no data to recommend revaccination after receiving the basic schedule for each type of vaccine. Both vaccines produce systemic and injection site adverse events of mild to moderate intensity.


Assuntos
Vacina contra Herpes Zoster/uso terapêutico , Herpes Zoster/prevenção & controle , Herpesvirus Humano 3 , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Vacinação , Vacinas Atenuadas/uso terapêutico
6.
BMC Infect Dis ; 19(1): 998, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31771522

RESUMO

BACKGROUND: Human group A rotavirus is the leading cause of severe acute gastroenteritis in young children worldwide. Immunization programs have reduced the disease burden in many countries. Vaccination coverage in the Autonomous Region of Valencia, Spain, is around 40%, as the rotavirus vaccine is not funded by the National Health System. Despite this low-medium vaccine coverage, rotavirus vaccination has substantially reduced hospitalizations due to rotavirus infection and hospital-related costs. However, there are very few studies evaluating symptomatic rotavirus infections not requiring hospitalization in vaccinated children. The objective of this study was to investigate symptomatic rotavirus infections among vaccinated children in the health area served by the Hospital Clínico Universitario of Valencia, Spain, from 2013 to 2015. METHODS: A total of 133 children younger than 5 years of age with rotavirus infection were studied. Demographic and epidemiological data were collected and informed consent from their caretakers obtained. Rotavirus infection was detected by immunological methods and G/P rotavirus genotypes were determined by RT-PCR, following standard procedures from the EuroRotaNet network. RESULTS: Forty infants (30.1%; 95% CI: 22.3-37.9) out of 133 were diagnosed with symptomatic rotavirus infection despite having been previously vaccinated, either with RotaTeq (85%) or with Rotarix (15%). Children fully vaccinated against rotavirus (24.8%), partially vaccinated (5.3%) and unvaccinated (69.9%) were found. The infecting genotypes showed high G-type diversity, although no significant differences were found between the G/P genotypes infecting vaccinated and unvaccinated children during the same time period. G9P[8], G12P[8] and G1P[8] were the most prevalent genotypes. Severity of gastroenteritis symptoms required 28 (66.6%) vaccinated and 67 (73.6%) unvaccinated children to be attended at the Emergency Room. CONCLUSION: Rotavirus vaccine efficacy in reducing the incidence of severe rotavirus infection has been well documented, but symptomatic rotavirus infection can sometimes occur in vaccinees.


Assuntos
Infecções por Rotavirus/etiologia , Vacinas contra Rotavirus/uso terapêutico , Rotavirus/genética , Estudos de Casos e Controles , Pré-Escolar , Feminino , Gastroenterite/etiologia , Gastroenterite/virologia , Genótipo , Humanos , Lactente , Masculino , Rotavirus/patogenicidade , Infecções por Rotavirus/prevenção & controle , Espanha , Cobertura Vacinal , Vacinas Atenuadas/uso terapêutico
7.
Pediatrics ; 144(4)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31530719

RESUMO

BACKGROUND: Rotavirus vaccine has been funded for infants under the Australian National Immunisation Program since 2007, with Rotarix vaccine used in New South Wales, Australia, from that time. In 2017, New South Wales experienced a large outbreak of rotavirus gastroenteritis. We examined epidemiology, genotypic profiles, and vaccine effectiveness (VE) among cases. METHODS: Laboratory-confirmed cases of rotavirus notified in New South Wales between January 1, 2010 and December 31, 2017 were analyzed. VE was estimated in children via a case-control analysis. Specimens from a sample of hospitalized case patients were genotyped and analyzed. RESULTS: In 2017, 2319 rotavirus cases were reported, representing a 3.1-fold increase on the 2016 notification rate. The highest rate was among children aged <2 years. For notified cases in 2017, 2-dose VE estimates were 88.4%, 83.7%, and 78.7% in those aged 6 to 11 months, 1 to 3 years, and 4 to 9 years, respectively. VE was significantly reduced from 89.5% within 1 year of vaccination to 77.0% at 5 to 10 years postvaccination. Equinelike G3P[8] (48%) and G8P[8] (23%) were identified as the most common genotypes in case patients aged ≥6 months. CONCLUSIONS: Rotarix is highly effective at preventing laboratory-confirmed rotavirus in Australia, especially in infants aged 6 to 11 months. Reduced VE in older age groups and over time suggests waning protection, possibly related to the absence of subclinical immune boosting from continuously circulating virus. G8 genotypes have not been common in Australia, and their emergence, along with equinelike G3P[8], may be related to vaccine-induced selective pressure; however, further strain-specific VE studies are needed.


Assuntos
Surtos de Doenças , Gastroenterite/epidemiologia , Infecções por Rotavirus/epidemiologia , Vacinas contra Rotavirus/uso terapêutico , Rotavirus/genética , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Notificação de Doenças/estatística & dados numéricos , Feminino , Gastroenterite/imunologia , Gastroenterite/prevenção & controle , Genótipo , Humanos , Programas de Imunização , Imunogenicidade da Vacina , Lactente , Masculino , Pessoa de Meia-Idade , New South Wales/epidemiologia , Rotavirus/imunologia , Infecções por Rotavirus/imunologia , Infecções por Rotavirus/prevenção & controle , Resultado do Tratamento , Vacinas Atenuadas/uso terapêutico , Adulto Jovem
8.
Artigo em Inglês | MEDLINE | ID: mdl-31300124

RESUMO

S. Choleraesuis (Choleraesuis) and S. Typhimurium (Typhimurium) cause salmonellosis in pigs and humans. The effects of vaccine strains pSV-less Typhimurium OU5048 and Choleraesuis OU7266 and SPI-2-mutant Choleraesuis SC2284 on the immune responses of pigs against Typhimurium, Choleraesuis, and S. Enteritidis (Enteritidis) with or without the virulence plasmid (pSV) were determined. After oral vaccination of three vaccine groups and challenge with Choleraesuis CN36, the level of Salmonella-specific IgG in sera and the bactericidal effects and superoxide generation of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear leukocytes (PMNs) against the above strains were determined using ELISA and NBT assay, respectively. Among three vaccine strains tested, OU7266 stimulated the highest Salmonella-specific IgG levels. Complement inactivation increased IgG concentration, while E. coli absorption reduced IgG levels. The pSV-containing strains were less resistant to serum killing than the pSV-less strains, and Enteritidis exhibited the lowest resistance to serum killing. Serovars tested, vaccine strains, and timeline periods postvaccination and challenge were important factors affecting superoxide production. The two Choleraesuis vaccine strains stimulated greater levels of superoxide from PMNs and PBMCs than the Typhimurium strains. The PMNs and PBMCs in challenged and vaccinated pigs reduced more superoxide than those in challenged hosts. In vaccinated hosts, pSV-less Salmonella strains triggered lower levels of PMN/PBMC-generated superoxide upon challenge than strains with pSV against Enteritidis and Choleraesuis. Overall, Choleraesuis OU7266 may be better than the other vaccine strains in generating the greatest IgG levels, serum bactericidal activity and superoxide levels. The pSV likely influences the immune responses.


Assuntos
Imunoglobulina G/sangue , Salmonelose Animal/prevenção & controle , Vacinas contra Salmonella/uso terapêutico , Doenças dos Suínos/prevenção & controle , Animais , Anticorpos Antibacterianos/sangue , Proteínas do Sistema Complemento/imunologia , Escherichia coli/imunologia , Escherichia coli/metabolismo , Feminino , Leucócitos Mononucleares/imunologia , Neutrófilos/imunologia , Espécies Reativas de Oxigênio/imunologia , Salmonella , Salmonelose Animal/imunologia , Vacinas contra Salmonella/imunologia , Salmonella typhimurium , Ensaios de Anticorpos Bactericidas Séricos , Suínos , Vacinação/veterinária , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêutico
9.
BMC Infect Dis ; 19(1): 453, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31117986

RESUMO

BACKGROUND: High hemagglutination inhibition (HAI) and neuraminidase inhibition (NAI) titers are generally associated with reduced influenza risk. While repeated influenza vaccination reduces seroresponse, vaccine effectiveness is not always reduced. METHODS: During the 2007-2008 influenza season, a randomized, placebo-controlled trial (FLUVACS) evaluated the efficacies of live-attenuated (LAIV) and inactivated influenza vaccines (IIV) among healthy adults aged 18-49 in Michigan; IIV vaccine efficacy (VE) and LAIV VE against influenza disease were estimated at 68% and 36%. Using the principal stratification/VE moderation framework, we analyzed data from this trial to assess how each VE varied by HAI or NAI responses to vaccination observed for vaccinated individuals and predicted counterfactually for placebo recipients. We also assessed how each VE varied with pre-vaccination/baseline variables including HAI titer, NAI titer, and vaccination history. RESULTS: IIV VE appeared to increase with Day 30 post-vaccination HAI titer, albeit not significantly (p=0.20 and estimated VE 14.4%, 70.5%, and 85.5% at titer below the assay lower quantification limit, 512, and 4096 (maximum)). Moreover, IIV VE increased significantly with Day 30 post-vaccination NAI titer (p=0.040), with estimated VE zero at titer 10 and 92.2% at highest titer 640. There was no evidence that fold-change in post-vaccination HAI or NAI titer associated with IIV VE (p=0.76, 0.38). For LAIV, there was no evidence that VE associated with post-vaccination or fold-rise HAI or NAI titers (p-values >0.40). For IIV, VE increased with increasing baseline NAI titer in those previously vaccinated, but VE decreased with increasing baseline NAI titer in those previously unvaccinated. In contrast, for LAIV, VE did not depend on previous vaccination or baseline HAI or NAI titer. CONCLUSIONS: Future efficacy trials should measure baseline and post-vaccination antibody titers in both vaccine and control/placebo recipients, enabling analyses to better elucidate correlates of vaccine- and natural-protection. TRIAL REGISTRATION: ClinicalTrials.gov NCT00538512. October 1, 2007.


Assuntos
Testes de Inibição da Hemaglutinação , Vacinas contra Influenza/uso terapêutico , Vacinas Atenuadas/uso terapêutico , Vacinas de Produtos Inativados/uso terapêutico , Adolescente , Adulto , Humanos , Imunogenicidade da Vacina , Testes Imunológicos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Pessoa de Meia-Idade , Neuraminidase/antagonistas & inibidores , Placebos , Fatores de Tempo , Vacinas Atenuadas/imunologia , Vacinas de Produtos Inativados/imunologia
10.
Value Health Reg Issues ; 18: 91-96, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30878901

RESUMO

OBJECTIVES: To examine the budget impact of introducing the RotaTeq® vaccine (Merck and Co Inc, West Point, PA) to the national immunization program in Iran. METHODS: The pre- and postvaccine introduction costs were compared. The total annual costs included the vaccination and diarrhea treatment costs. The health outcome was the estimated annual cases of the disease. To evaluate the net budget impact, the annual prevaccine introduction cost was reduced from the postvaccine introduction cost. The sensitivity analysis was done to reduce the uncertainties. RESULTS: The total cost of vaccination for 5 years would be more than $184 million. Nevertheless, the financial savings would be about $45 million and $7.5 million because of the reduction in the number of patients after vaccination in inpatient and outpatient sectors, respectively. So the incremental cost would be $131 450 210 during 5 years of immunization. CONCLUSIONS: The results show that the inclusion of rotavirus vaccine in the national vaccination program would have a significant effect on health budgets and would raise government expenditure.


Assuntos
Esquemas de Imunização , Vacinas contra Rotavirus/administração & dosagem , Vacinas contra Rotavirus/economia , Análise Custo-Benefício , Humanos , Programas de Imunização/economia , Irã (Geográfico) , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/uso terapêutico , Vacinas Atenuadas/economia , Vacinas Atenuadas/uso terapêutico
11.
J Infect Public Health ; 12(5): 625-629, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30837151

RESUMO

BACKGROUND: Rotavirus gastroenteritis accounts for significant childhood morbidity and mortality worldwide. Vaccination using RotarixTM (GSK) and RotaTeq® (Merck) was introduced due to the tremendous disease burden. The possibility of asymptomatic infections following vaccinations was poorly understood. This study examined rotavirus cases in post-vaccinated children, their clinical manifestations and the genotypes of isolated strains. METHODS: Stool samples of healthy, vaccinated children under 5 years of age in Surabaya were collected monthly for 1 year between January 2016 and February 2017. Episodes of gastroenteritis were reported, and samples were collected. Rotavirus was identified using multiplex reverse transcription Polymerase Chain Reaction (QIAGEN, Inc., Valencia, CA). Clinical manifestations were measured using the Vesikari score. The genotype was analyzed by Applied Biosystems (Foster, CA). RESULTS: A total of 109 stool samples were collected from 30 subjects, of which 22 received Rotarix; 8 RotaTeq. Nine out of 109 samples were collected during diarrhea episodes of 8 subjects. Two asymptomatic rotavirus infections were identified by RT-PCR. The genotypes isolated were G1P[8] and G3P[8]. CONCLUSIONS: Asymptomatic rotavirus infections can occur in post-vaccinated children. Strains identified were homologous to serotypes eliciting gastroenteritis in unvaccinated children of the same community.


Assuntos
Infecções Assintomáticas/epidemiologia , Gastroenterite/virologia , Infecções por Rotavirus/epidemiologia , Vacinas contra Rotavirus/uso terapêutico , Pré-Escolar , Fezes/virologia , Feminino , Gastroenterite/epidemiologia , Variação Genética , Genótipo , Humanos , Indonésia/epidemiologia , Lactente , Masculino , RNA Viral/genética , Rotavirus/genética , Rotavirus/isolamento & purificação , Infecções por Rotavirus/prevenção & controle , Sorogrupo , Vacinas Atenuadas/uso terapêutico
12.
Virol Sin ; 34(3): 243-252, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30911897

RESUMO

The incidence of Japanese encephalitis (JE) has significantly decreased in China due to JE vaccines. In this study, we investigated the post-JE vaccination seroprevalence and protection provided by vaccinated sera against Japanese encephalitis virus (JEV) to elucidate the persistence and waning of antibodies to JEV among JE-SA14-14-2-vaccinated children. A total of 300 serum samples were collected from vaccinated children aged 3-10 years in Zhaotong, Yunnan, China. The seroprevalence of anti-JEV antibodies was determined by enzyme-linked immune sorbent assay and plaque reduction neutralization test. The highest seropositivity of 82% was observed in vaccinated children during the first 0.5-1.5 years after booster vaccination. Then, the seropositivity began to decline and remained lower than the original level observed in the 0.5-1.5-year group. An association was found between the waning of seroprevalence and elapsed time of the post-booster vaccination. Similarly, the neutralizing antibody (nAb) titres gradually decreased over time, and the levels showed a positive correlation with the protective efficacy in mice. This finding suggests that nAbs play an important role in the antiviral process and that the nAb titre is an adequately credible parameter for evaluating the protective efficacy induced by the JE vaccine. Our results provide data that clarify the persistence and waning of antibodies to JEV, which may help elucidate the pathogenesis of JE.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Encefalite Japonesa/prevenção & controle , Vacinas contra Encefalite Japonesa/uso terapêutico , Transferência Adotiva , Animais , Criança , Pré-Escolar , China/epidemiologia , Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunização Secundária/estatística & dados numéricos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Neutralização , Estudos Soroepidemiológicos , Vacinação/estatística & dados numéricos , Vacinas Atenuadas/uso terapêutico
13.
Cochrane Database Syst Rev ; 3: CD008521, 2019 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-30912133

RESUMO

BACKGROUND: Rotavirus results in more diarrhoea-related deaths in children under five years than any other single agent in countries with high childhood mortality. It is also a common cause of diarrhoea-related hospital admissions in countries with low childhood mortality. Rotavirus vaccines that have been prequalified by the World Health Organization (WHO) include a monovalent vaccine (RV1; Rotarix, GlaxoSmithKline), a pentavalent vaccine (RV5; RotaTeq, Merck), and, more recently, another monovalent vaccine (Rotavac, Bharat Biotech). OBJECTIVES: To evaluate rotavirus vaccines prequalified by the WHO (RV1, RV5, and Rotavac) for their efficacy and safety in children. SEARCH METHODS: On 4 April 2018 we searched MEDLINE (via PubMed), the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (published in the Cochrane Library), Embase, LILACS, and BIOSIS. We also searched the WHO ICTRP, ClinicalTrials.gov, clinical trial reports from manufacturers' websites, and reference lists of included studies and relevant systematic reviews. SELECTION CRITERIA: We selected randomized controlled trials (RCTs) in children comparing rotavirus vaccines prequalified for use by the WHO versus placebo or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial eligibility and assessed risks of bias. One review author extracted data and a second author cross-checked them. We combined dichotomous data using the risk ratio (RR) and 95% confidence interval (CI). We stratified the analysis by country mortality rate and used GRADE to evaluate evidence certainty. MAIN RESULTS: Fifty-five trials met the inclusion criteria and enrolled a total of 216,480 participants. Thirty-six trials (119,114 participants) assessed RV1, 15 trials (88,934 participants) RV5, and four trials (8432 participants) Rotavac.RV1 Children vaccinated and followed up the first year of life In low-mortality countries, RV1 prevents 84% of severe rotavirus diarrhoea cases (RR 0.16, 95% CI 0.09 to 0.26; 43,779 participants, 7 trials; high-certainty evidence), and probably prevents 41% of cases of severe all-cause diarrhoea (RR 0.59, 95% CI 0.47 to 0.74; 28,051 participants, 3 trials; moderate-certainty evidence). In high-mortality countries, RV1 prevents 63% of severe rotavirus diarrhoea cases (RR 0.37, 95% CI 0.23 to 0.60; 6114 participants, 3 trials; high-certainty evidence), and 27% of severe all-cause diarrhoea cases (RR 0.73, 95% CI 0.56 to 0.95; 5639 participants, 2 trials; high-certainty evidence).Children vaccinated and followed up for two yearsIn low-mortality countries, RV1 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.14 to 0.23; 36,002 participants, 9 trials; high-certainty evidence), and probably prevents 37% of severe all-cause diarrhoea episodes (rate ratio 0.63, 95% CI 0.56 to 0.71; 39,091 participants, 2 trials; moderate-certainty evidence). In high-mortality countries RV1 probably prevents 35% of severe rotavirus diarrhoea cases (RR 0.65, 95% CI 0.51 to 0.83; 13,768 participants, 2 trials; high-certainty evidence), and 17% of severe all-cause diarrhoea cases (RR 0.83, 95% CI 0.72 to 0.96; 2764 participants, 1 trial; moderate-certainty evidence).No increased risk of serious adverse events (SAE) was detected (RR 0.88 95% CI 0.83 to 0.93; high-certainty evidence). There were 30 cases of intussusception reported in 53,032 children after RV1 vaccination and 28 cases in 44,214 children after placebo or no intervention (RR 0.70, 95% CI 0.46 to 1.05; low-certainty evidence).RV5 Children vaccinated and followed up the first year of life In low-mortality countries, RV5 probably prevents 92% of severe rotavirus diarrhoea cases (RR 0.08, 95% CI 0.03 to 0.22; 4132 participants, 5 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 57% of severe rotavirus diarrhoea (RR 0.43, 95% CI 0.29 to 0.62; 5916 participants, 2 trials; high-certainty evidence), but there is probably little or no difference between vaccine and placebo for severe all-cause diarrhoea (RR 0.80, 95% CI 0.58 to 1.11; 1 trial, 4085 participants; moderate-certainty evidence).Children vaccinated and followed up for two yearsIn low-mortality countries, RV5 prevents 82% of severe rotavirus diarrhoea cases (RR 0.18, 95% CI 0.08 to 0.39; 7318 participants, 4 trials; moderate-certainty evidence). We did not identify studies reporting on severe all-cause diarrhoea in low-mortality countries. In high-mortality countries, RV5 prevents 41% of severe rotavirus diarrhoea cases (RR 0.59, 95% CI 0.43 to 0.82; 5885 participants, 2 trials; high-certainty evidence), and 15% of severe all-cause diarrhoea cases (RR 0.85, 95% CI 0.75 to 0.98; 5977 participants, 2 trials; high-certainty evidence).No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.86 to 1.01; moderate to high-certainty evidence). There were 16 cases of intussusception in 43,629 children after RV5 vaccination and 20 cases in 41,866 children after placebo (RR 0.77, 95% CI 0.41 to 1.45; low-certainty evidence).Rotavac Children vaccinated and followed up the first year of life Rotavac has not been assessed in any RCT in countries with low child mortality. In India, a high-mortality country, Rotavac probably prevents 57% of severe rotavirus diarrhoea cases (RR 0.43, 95% CI 0.30 to 0.60; 6799 participants, moderate-certainty evidence); the trial did not report on severe all-cause diarrhoea at one-year follow-up.Children vaccinated and followed up for two yearsRotavac probably prevents 54% of severe rotavirus diarrhoea cases in India (RR 0.46, 95% CI 0.35 to 0.60; 6541 participants, 1 trial; moderate-certainty evidence), and 16% of severe all-cause diarrhoea cases (RR 0.84, 95% CI 0.71 to 0.98; 6799 participants, 1 trial; moderate-certainty evidence).No increased risk of serious adverse events (SAE) was detected (RR 0.93 95% CI 0.85 to 1.02; moderate-certainty evidence). There were eight cases of intussusception in 5764 children after Rotavac vaccination and three cases in 2818 children after placebo (RR 1.33, 95% CI 0.35 to 5.02; very low-certainty evidence).There was insufficient evidence of an effect on mortality from any rotavirus vaccine (198,381 participants, 44 trials; low- to very low-certainty evidence), as the trials were not powered to detect an effect at this endpoint. AUTHORS' CONCLUSIONS: RV1, RV5, and Rotavac prevent episodes of rotavirus diarrhoea. Whilst the relative effect estimate is smaller in high-mortality than in low-mortality countries, there is a greater number of episodes prevented in these settings as the baseline risk is much higher. We found no increased risk of serious adverse events.


Assuntos
Diarreia Infantil/prevenção & controle , Diarreia/prevenção & controle , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/uso terapêutico , Adulto , Criança , Pré-Escolar , Diarreia/virologia , Diarreia Infantil/virologia , Humanos , Lactente , Recém-Nascido , Ensaios Clínicos Controlados Aleatórios como Assunto , Vacinas contra Rotavirus/classificação , Vacinas Atenuadas/uso terapêutico , Adulto Jovem
14.
Viruses ; 11(2)2019 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-30717342

RESUMO

Avian respiratory disease causes significant economic losses in commercial poultry. Because of the need to protect long-lived poultry against respiratory tract pathogens from an early age, vaccination programs for pullets typically involve serial administration of a variety of vaccines, including infectious bronchitis virus (IBV), Newcastle disease virus (NDV), and infectious laryngotracheitis virus (ILTV). Often the interval between vaccinations is only a matter of weeks, yet it is unknown whether the development of immunity and protection against challenge when vaccines are given in short succession occurs in these birds, something known as viral interference. Our objective was to determine whether serially administered, live attenuated vaccines against IBV, NDV, and ILTV influence the development and longevity of immunity and protection against challenge in long-lived birds. Based on a typical pullet vaccination program, specific-pathogen-free white leghorns were administered multiple live attenuated vaccines against IBV, NDV, and ILTV until 16 weeks of age (WOA), after which certain groups were challenged with IBV, NDV, or ILTV at 20, 24, 28, 32, and 36 WOA. Five days post-challenge, viral load, clinical signs, ciliostasis, tracheal histopathology, and antibody titers in serum and tears were evaluated. We demonstrate that pullets serially administered live attenuated vaccines against IBV, NDV, and ILTV were protected against homologous challenge with IBV, NDV, or ILTV for at least 36 weeks, and conclude that the interval between vaccinations used in this study (at least 2 weeks) did not interfere with protection. This information is important because it shows that a typical pullet vaccination program consisting of serially administered live attenuated vaccines against multiple respiratory pathogens can result in the development of protective immunity against each disease agent.


Assuntos
Infecções por Coronavirus/veterinária , Infecções por Herpesviridae/veterinária , Longevidade , Doenças das Aves Domésticas/prevenção & controle , Vacinas Virais/uso terapêutico , Animais , Anticorpos Antivirais/sangue , Galinhas , Infecções por Coronavirus/prevenção & controle , Feminino , Infecções por Herpesviridae/prevenção & controle , Herpesvirus Galináceo 1 , Vírus da Bronquite Infecciosa , Vírus da Doença de Newcastle , Doenças das Aves Domésticas/virologia , Organismos Livres de Patógenos Específicos , Vacinação/veterinária , Vacinas Atenuadas/uso terapêutico
15.
Cancer Lett ; 448: 168-181, 2019 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-30753837

RESUMO

Bacteria have been investigated as anti-tumor therapeutic agents for more than a century, since Coley first observed successful curing of a patient with inoperable cancer by injection of streptococcal organisms. Previous studies have demonstrated that some obligate or facultative anaerobes can selectively accumulate and proliferate within tumors and suppress their growth. Developments in molecular biology as well as the complete genome sequencing of many bacterial species have increased the applicability of bacterial organisms for cancer treatment. In particular, the facultative anaerobe Salmonella Typhimurium has been widely studied and genetically engineered to improve its tumor-targeting ability as well as to reduce bacterial virulence. Moreover, the effectiveness of engineered attenuated S. Typhimurium strains employed as live delivery vectors of various anti-tumor therapeutic agents or combined with other therapies has been evaluated in a large number of animal experiments. The well-known S. Typhimurium mutant VNP20009 and its derivative strain TAPET-CD have even been applied in human clinical trials. However, Salmonella-mediated cancer therapies have not achieved the expected success, except in animal experiments. Many problems remain to be solved to exploit more promising strategies for combatting cancer with Salmonella bacteria. Here, we summarize the promising studies regarding cancer therapy mediated by Salmonella bacteria and highlight the main mechanisms of Salmonella anti-tumor activities.


Assuntos
Antineoplásicos/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Neoplasias/terapia , Salmonella typhimurium/imunologia , Vacinas Atenuadas/uso terapêutico , Animais , Humanos
16.
Pediatrics ; 143(2)2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30617239

RESUMO

BACKGROUND: Researchers in observational studies of vaccine effectiveness (VE) in which they compared quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) among children and adolescents have shown inconsistent results, and the studies have been limited by small samples. METHODS: We combined data from 5 US studies from 2013-2014 through 2015-2016 to compare the VE of LAIV4 and IIV against medically attended, laboratory-confirmed influenza among patients aged 2 to 17 years by influenza season, subtype, age group, and prior vaccination status. The VE of IIV or LAIV4 was calculated as 100% × (1 - odds ratio), comparing the odds of vaccination among patients who were influenza-positive to patients who were influenza-negative from adjusted logistic regression models. Relative effectiveness was defined as the odds of influenza comparingLAIV4 and IIV recipients. RESULTS: Of 17 173 patients aged 2 to 17 years, 4579 received IIV, 1979 received LAIV4, and 10 615 were unvaccinated. Against influenza A/H1N1pdm09, VE was 67% (95% confidence interval [CI]: 62% to 72%) for IIV and 20% (95% CI: -6% to 39%) for LAIV4. Results were similar when stratified by vaccination in the previous season. LAIV4 recipients had significantly higher odds of influenza A/H1N1pdm09 compared with IIV recipients (odds ratio 2.66; 95% CI: 2.06 to 3.44). LAIV4 and IIV had similar effectiveness against influenza A/H3N2 and B. Our overall findings were consistent when stratified by influenza season and age group. CONCLUSIONS: From this pooled individual patient-level data analysis, we found reduced effectiveness of LAIV4 against influenza A/H1N1pdm09 compared with IIV, which is consistent with published results from the individual studies included.


Assuntos
Vacinas contra Influenza/uso terapêutico , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Influenza Humana/diagnóstico , Masculino , Resultado do Tratamento , Estados Unidos/epidemiologia , Vacinas Atenuadas/uso terapêutico , Vacinas de Produtos Inativados/uso terapêutico
17.
Clin Microbiol Infect ; 25(1): 102-106, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29649603

RESUMO

OBJECTIVES: Rotavirus infections are common causes of infant hospitalization. The present study examined the effectiveness of anti-rotavirus vaccination in preventing rotavirus-related hospitalizations in Germany, following its state and nationwide introductions in 2008 and 2013, respectively. METHODS: During 15 consecutive seasons 9557 stool samples of hospitalized children of 5 years and younger with acute gastroenteritis were screened for rotavirus A. Rotavirus G and P genotypes were assessed after vaccine introduction. Vaccine effectiveness was determined by comparison of rotavirus incidence in pre-vaccine and post-vaccine cohorts. The herd effect was calculated as the difference between the observed reduction of rotavirus-related hospitalizations and the expected direct vaccine effect. RESULTS: The number of rotavirus-related hospitalizations declined after vaccine introduction. Approximately 26% (503/1955) of prevented cases could be attributed to the herd effect. Human rotaviruses of genotypes G3P[8], G1P[8], G9P[8], G4P[8], G2P[4] and G12P[8] were most frequent. Uncommon genotypes remained rare. The direct, indirect, total and overall vaccine effectiveness was 86% (95% confidence interval (CI) 83.2-89.1%), 48% (95% CI 42.8-52.6%), 93% (95% CI 91.3-94.3%) and 69% (95% CI 66.5-72.0%), respectively. There was no significant difference in vaccine-type or in genotype-specific vaccine effectiveness. CONCLUSIONS: Anti-rotavirus vaccination efficiently reduced rotavirus-related hospitalizations in Germany in the past decade. The vaccines analysed in this article provide a broadly heterologous and long-lasting protection. The herd effect substantially contributed to the observed drop in the number of incidences of severe rotavirus infections. Presumably, constant high vaccine coverage will lead to a continued upward trend in the overall vaccine efficiency.


Assuntos
Gastroenterite/epidemiologia , Gastroenterite/prevenção & controle , Hospitalização/estatística & dados numéricos , Infecções por Rotavirus/prevenção & controle , Vacinas contra Rotavirus/uso terapêutico , Pré-Escolar , Fezes/virologia , Feminino , Genótipo , Alemanha/epidemiologia , Humanos , Imunidade Coletiva , Incidência , Lactente , Masculino , Rotavirus , Infecções por Rotavirus/epidemiologia , Vacinas contra Rotavirus/imunologia , Vacinação/estatística & dados numéricos , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêutico
18.
Antiviral Res ; 162: 1-4, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30529359

RESUMO

Yellow fever is a serious disease caused by infection with the yellow fever virus (YFV). A live-attenuated YFV vaccine strain, 17D (YFV-17D) is the only virus strain available for the production of the YFV vaccine. This study evaluated the immunogenicity and immune persistence of vaccination with YFV-17D and identified their influencing factors in Chinese peacekeepers deployed to Africa. Serum specimens were collected before and ≥21 days after primary vaccination with YFV-17D in 349 Chinese peacekeepers who were subsequently deployed to Africa for the first time from 2016 to 2017 (population 1). Serum specimens were collected from 1 to 11 years after vaccination with YFV-17D in 2062 returned Chinese peacekeepers who were deployed to Africa from 2005 to 2015 (population 2). We found that YFV-17D exhibited an excellent protective effect in the Chinese peacekeepers deployed to Africa early following vaccination. In the Chinese peacekeepers one year after vaccination, the serum antibody titer against YFV increased with increasing age at vaccination; in those two or more years after vaccination, the serum antibody titer against YFV decreased over years and was similar to but greater than the minimum protective level 11 years after vaccination. The number of peacekeeping missions exhibited an almost negligible influence on the serum antibody titer against YFV. (This study has been registered at International Clinical Trials Registry Platform (http://www.who.int/ictrp/en/) under registration Nos. ChiCTR1800017024.).


Assuntos
Anticorpos Antivirais/sangue , Imunogenicidade da Vacina , Vacina contra Febre Amarela/uso terapêutico , Febre Amarela/prevenção & controle , Adolescente , Adulto , África , Fatores Etários , Grupo com Ancestrais do Continente Asiático , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Militares , Fatores de Tempo , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêutico , Febre Amarela/sangue , Febre Amarela/imunologia , Vacina contra Febre Amarela/imunologia , Vírus da Febre Amarela , Adulto Jovem
19.
Mem. Inst. Oswaldo Cruz ; 114: e180571, 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1002691

RESUMO

BACKGROUND TcP21 is a ubiquitous secreted protein of Trypanosoma cruzi and its recombinant form (rP21) promotes parasite cell invasion and acts as a phagocytosis inducer by activating actin polymerisation in the host cell. OBJECTIVE Our goal was to evaluate if the additional supplementation of rP21 during a prime/boost/challenge scheme with T. cruzi TCC attenuated parasites could modify the well-known protective behavior conferred by these parasites. METHODS The humoral immune response was evaluated through the assessment of total anti-T. cruzi antibodies as well as IgG subtypes. IFN-γ, TNF-α and IL-10 were measured in supernatants of splenic cells stimulated with total parasite homogenate or rP21. FINDINGS Our results demonstrated that, when comparing TCC+rP21 vs. TCC vaccinated animals, the levels of IFN-γ were significantly higher in the former group, while the levels of IL-10 and TNF-α were significantly lower. Further, the measurement of parasite load after lethal challenge showed an exacerbated infection and parasite load in heart and skeletal muscle after pre-treatment with rP21, suggesting the important role of this protein during parasite natural invasion process. MAIN CONCLUSION Our results demonstrated that rP21 may have adjuvant capacity able to modify the cytokine immune profile elicited by attenuated parasites.


Assuntos
Humanos , Vacinas Atenuadas/uso terapêutico , Proteínas rho de Ligação ao GTP/análise , Trypanosoma cruzi , Doença de Chagas/transmissão
20.
Toxins (Basel) ; 10(12)2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30513757

RESUMO

Nonencapsulated (∆pXO2) Bacillus anthracis strains are commonly used as vaccines and for anthrax research, mainly in the mouse model. Previously, we demonstrated that the infection of rabbits, intranasally or subcutaneously, with the spores of a fully virulent strain results in the systemic dissemination of the bacteria, meningitis, and death, whereas ∆pXO2 strains are fully attenuated in this animal model. We used the intravenous inoculation of rabbits to study the pathogenicity of the ∆pXO2 strain infection. Bacteremia, brain bacterial burden, and pathology were used as criteria to compare the Vollum∆pXO2 disease to the wild type Vollum infection. To test the role of adhesion in the virulence of Vollum∆pXO2, we deleted the major adhesion protein BslA and tested the virulence and immunogenicity of this mutant. We found that 50% of the rabbits succumb to Vollum∆pXO2 strain following i.v. infection, a death that was accompanied with significant neurological symptoms. Pathology revealed severe brain infection coupled with an atypical massive bacterial growth into the parenchyma. Contrary to the Vollum strain, deletion of the bslA gene fully attenuated the ∆pXO2 strain. Though the Vollum∆pXO2 cannot serve as a model for B. anthracis pathogenicity in rabbits, deletion of the bslA gene prevents central nervous system (CNS) infections, possibly leading to the generation of a safer vaccine.


Assuntos
Antraz/prevenção & controle , Bacillus anthracis/fisiologia , Aderência Bacteriana , Proteínas de Bactérias/genética , Vacinas Atenuadas/uso terapêutico , Animais , Antraz/microbiologia , Antraz/patologia , Bacillus anthracis/patogenicidade , Encéfalo/microbiologia , Encéfalo/patologia , Células Cultivadas , Células Endoteliais/fisiologia , Feminino , Mutação , Coelhos
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