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1.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(1): 103-110, 2020 Jan 10.
Artigo em Chinês | MEDLINE | ID: mdl-32062951

RESUMO

Objective: To evaluate the effectiveness of live attenuated influenza vaccine (LAIV) in the prevention of seasonal influenza in children aged 2-17 years. Methods: Literature retrieval of case-control studies on the effectiveness of LAIV against seasonal influenza in children published from January 2003 to November 2018 was conducted through Web of Science, PubMed, and ScienceDirect databases. The Stata 13.1 software was used for Meta-analysis. Results: A total of 14 studies were included in this study, and all were test-negative design (TND) studies. Our Meta-analysis showed that the effectiveness of LAIV in children was 49% (95%CI: 40%-57%). Subgroup analysis found that the protection rate of LAIV was 35% against influenza A (H1N1) pdm09 (95%CI: 5%-56%), 35% against influenza A (H3N2) (95%CI: 21%-46%), and 71% against influenza B (95%CI: 55%-82%). The protection rates of trivalent LAIV and quadrivalent LAIV in children were 56% (95%CI: 48%-63%) and 44% (95%CI: 27%-57%), respectively. The protection rates of LAIV in Europe and North America were 65% (95%CI: 47%-77%) and 46% (95%CI: 36%-55%), respectively. Conclusion: LAIV has a certain preventive effect on seasonal influenza in children aged 2-17 years.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza , Influenza Humana , Adolescente , Criança , Pré-Escolar , Humanos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Estações do Ano , Vacinas Atenuadas
2.
Exp Parasitol ; 210: 107849, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32027892

RESUMO

Cutaneous Leishmaniasis is a serious public health problem, typically affecting poor populations with limited access to health care. Control is largely dependent on chemotherapies that are inefficient, costly and challenging to deliver. Vaccination is an attractive and feasible alternative because long-term protection is typical in patients who recover from the disease. No human vaccine is yet approved for use, but several candidates are at various stages of testing. Live attenuated parasites, which stimulate long-term immune protection, have potential as effective vaccines, and their challenges relating to safety, formulation and delivery can be overcome. Here we review current data on the potential of live attenuated Leishmania vaccines and discuss possible routes to regulatory approval.


Assuntos
Leishmania/imunologia , Leishmaniose Cutânea/prevenção & controle , Vacinas Protozoárias , Animais , Modelos Animais de Doenças , Humanos , Vacinas Atenuadas
4.
J Zoo Wildl Med ; 50(4): 778-789, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31926507

RESUMO

Data on canine distemper virus (CDV) vaccination were collected on 812 large felids (351 tigers, Panthera tigris; 220 lions, Panthera leo; 143 snow leopards, Panthera uncia; 50 leopards, Panthera pardus; and 48 jaguars, Panthera onca) from 48 institutions to assess vaccine use and safety. The documented individual vaccination events with multiple products numbered 2,846. Canarypox-vectored CDV vaccines were the most commonly used vaccines (96.3% of all vaccinations) and the Purevax® Ferret Distemper (PFD) vaccine was the most commonly used canarypox-vectored vaccine (91.0% of all vaccinations). Modified live virus (MLV) CDV vaccines were used for 3.7% of all vaccinations, and only in tigers, lions, and snow leopards. Adverse effects were reported after 0.5% (13 of 2,740) of the canarypox-vectored vaccinations and after 2.9% (3 of 104) of the MLV CDV vaccinations. This low complication rate suggests large felids may not be as sensitive to adverse effects of MLV CDV vaccines as other exotic carnivores. Serological data were available from 159 individuals (69 tigers, 31 lions, 31 snow leopards, 22 jaguars, and 6 Amur leopards, Panthera pardus orientalis) vaccinated with the PFD vaccine, and 66.0% of vaccinates seroconverted (defined as acquiring a titer ≥1: 24) at some point postvaccination: 24.3% after one vaccination, 55.8% after two vaccinations, 54.3% after three vaccinations, and 79.2% after four or more vaccinations. Among animals exhibiting seroconversion after the initial PFD vaccinations, 88.9% still had titers ≥12 mo and ≥24 mo after the last vaccination, and 87.5% had titers ≥1: 24 at ≥36 mo after the last vaccination. The study was unable to assess fully the safety of vaccination with either canarypox-vectored or MLV CDV vaccines during gestation because of the small number of animals vaccinated while pregnant (n = 6, all vaccinated with PFD).


Assuntos
Anticorpos Antivirais/sangue , Vírus da Cinomose Canina , Cinomose/prevenção & controle , Panthera/imunologia , Vacinas Virais/imunologia , Animais , Cinomose/epidemiologia , Feminino , Masculino , América do Norte/epidemiologia , Soroconversão , Vacinas Atenuadas
5.
J Med Microbiol ; 69(1): 111-119, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31778110

RESUMO

Introduction. Differences between the genomic and virulence profile of Bordetella pertussis circulating strains and vaccine strains are considered as one of the important reasons for the resurgence of whooping cough (pertussis) in the world. Genetically inactivated B. pertussis is one of the new strategies to generate live-attenuated vaccines against whooping cough.Aim. The aim of this study was to construct a B. pertussis strain based on a predominant profile of circulating Iranian isolates that produces inactivated pertussis toxin (PTX).Methodology. The B. pertussis strain BPIP91 with predominant genomic and virulence pattern was selected from the biobank of the Pasteur Institute of Iran. A BPIP91 derivative with R9K and E129G alterations in the S1 subunit of PTX (S1mBPIP91) was constructed by the site-directed mutagenesis and homologous recombination. Genetic stability and antigen expression of S1mBPIP91 were tested by serially in vitro passages and immunoblot analyses, respectively. The reduction in toxicity of S1mBPIP91 was determined by Chinese hamster ovary (CHO) cell clustering.Results. All constructs and S1mBPIP91 were confirmed via restriction enzyme analysis and DNA sequencing. The engineered mutations in S1mBPIP91 were stable after 20 serial in vitro passages. The production of virulence factors was also confirmed in S1mBPIP91. The CHO cell-clustering test demonstrated the reduction in PTX toxicity in S1mBPIP91.Conclusion. A B. pertussis of the predominant genomic and virulence lineage in Iran was successfully engineered to produce inactive PTX. This attenuated strain will be useful to further studies to develop both whole cell and acellular pertussis vaccines.


Assuntos
Antígenos de Bactérias/genética , Bordetella pertussis/genética , Bordetella pertussis/imunologia , Proteínas Mutantes/genética , Toxina Pertussis/genética , Vacina contra Coqueluche/genética , Animais , Antígenos de Bactérias/metabolismo , Antígenos de Bactérias/toxicidade , Células CHO , Sobrevivência Celular/efeitos dos fármacos , Cricetulus , Irã (Geográfico) , Mutagênese Sítio-Dirigida , Proteínas Mutantes/metabolismo , Proteínas Mutantes/toxicidade , Toxina Pertussis/metabolismo , Toxina Pertussis/toxicidade , Vacina contra Coqueluche/efeitos adversos , Engenharia de Proteínas , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/genética
6.
Artigo em Inglês | MEDLINE | ID: mdl-31784763

RESUMO

Dengue, the most common arbovirus, represents an increasingly significant cause of morbidity worldwide, including in travelers. After decades of research, the first dengue vaccine was licensed in 2015: CYD-TDV, a tetravalent live attenuated vaccine with a yellow fever vaccine backbone. Recent analyses have shown that vaccine performance is dependent on serostatus. In those who have had a previous dengue infection, i.e., who are seropositive, the efficacy is high and the vaccine is safe. However, in seronegative vaccinees, approximately 3 years after vaccination the vaccine increases the risk of developing severe dengue when the individual experiences a natural dengue infection.The World Health Organization recommends that this vaccine be administered only to seropositive individuals. Current efforts are underway to develop rapid diagnostic tests to facilitate prevaccination screening. Two second-generation dengue vaccine candidates, both also live attenuated recombinant vaccines in late-stage development, may not present the same limitations because of differences in the backbone used, but results of phase 3 trials need to be available before firm conclusions can be drawn.Dengue is increasingly frequent in travelers, but the only licensed dengue vaccine to date can be used only in seropositive individuals. However, the vast majority of travelers are seronegative. Furthermore, the primary series of three doses given 6 months apart renders this vaccine difficult in the travel medicine context.


Assuntos
Vacinas contra Dengue , Dengue , Anticorpos Antivirais , Alemanha , Humanos , Vacinação , Vacinas Atenuadas
7.
PLoS Negl Trop Dis ; 13(12): e0007490, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31790394

RESUMO

Schistosoma mansoni threatens hundreds of millions of people in >50 countries. Schistosomulae migrate through the lung and adult worms reside in blood vessels adjacent to the intestinal mucosa. Current candidate vaccines aren't designed to elicit a mucosal response. We have repurposed an attenuated Salmonella enterica Typhimurium strain (YS1646) to produce such a vaccine targeting Cathepsin B (CatB), a digestive enzyme important for parasite survival. Promoter-Type 3 secretory signal pairs were screened for protein expression in vitro and transfected into YS1646 to generate candidate vaccine strains. Two strains were selected for in vivo evaluation (nirB_SspH1 and SspH1_SspH1). Female C57BL/6 mice were immunized twice, 3 weeks apart, using six strategies: i) saline gavage (control), ii) the 'empty' YS1646 vector orally (PO) followed by intramuscular (IM) recombinant CatB (20µg IM rCatB), iii) two doses of IM rCatB, iv) two PO doses of YS1646-CatB, v) IM rCatB then PO YS1646-CatB and vi) PO YS1646-CatB then IM rCatB. Serum IgG responses to CatB were monitored by ELISA. Three weeks after the second dose, mice were challenged with 150 cercariae and sacrificed 7 weeks later to assess adult worm and egg burden (liver and intestine), granuloma size and egg morphology. CatB-specific IgG antibodies were low/absent in the control and PO only groups but rose substantially in other groups (5898-6766ng/mL). The highest response was in animals that received nirB_SspH1 YS1646 PO then IM rCatB. In this group, reductions in worm and intestine/liver egg burden (vs. control) were 93.1% and 79.5%/90.3% respectively (all P < .0001). Granuloma size was reduced in all vaccinated groups (range 32.9-52.8 x103µm2) and most significantly in the nirB_SspH1 + CatB IM group (34.7±3.4 x103µm2vs. 62.2±6.1 x103µm2: vs. control P < .01). Many eggs in the vaccinated animals had abnormal morphology. Targeting CatB using a multi-modality approach can provide almost complete protection against S. mansoni challenge.


Assuntos
Antígenos de Helmintos/imunologia , Catepsina B/imunologia , Portadores de Fármacos , Salmonella typhimurium/genética , Schistosoma mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Vacinas Sintéticas/imunologia , Animais , Anticorpos Anti-Helmínticos/sangue , Antígenos de Helmintos/genética , Catepsina B/genética , Modelos Animais de Doenças , Feminino , Imunoglobulina G/sangue , Injeções Intramusculares , Camundongos Endogâmicos C57BL , Schistosoma mansoni/genética , Esquistossomose mansoni/patologia , Resultado do Tratamento , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Vacinas Sintéticas/administração & dosagem
8.
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
9.
Acta Virol ; 63(4): 403-414, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31802683

RESUMO

The use of live attenuated vaccine (LAV) is the main method for controlling infectious bronchitis (IB). It is advisable to develop a LAV using a dominant serotype in the region in the case of vaccine failure. Since 793/B serotype is one of the most predominant circulating IB viruses in Iran, attenuation of three Iranian 793/B isolates (IR/773/2001, IR/794/2002 and IR/520/2002) was done by serial passaging in specific pathogen free (SPF) embryonated chicken eggs up to 90 passages to assess the degree of their attenuation to achieve a native LAV in the future. Virulence and pathogenicity of passage levels 15 and 90 of isolates 773 and 794 were compared using histopathology, ciliostasis and potency tests. The results showed a decrease in the virulence and pathogenicity of the isolates at passage 90 compared to passage 15, although this decrease in pathogenicity was very mild and viruses after passage 90 were not adequately attenuated. Each isolate underwent some amino acid changes at passage 90. In case of isolate 773 it was 5 aa changes, while in isolate 794 it was 19 aa changes. Some amino acid changes resulted in change into amino acid with different hydrophobicity characteristics. No amino acid change was found at passage level 15 compared to wild type viruses. Interestingly, we did not find previously reported change in amino acid 95 in passage levels 15 and 90. Keywords: infectious bronchitis; live attenuated vaccine; 793/B serotype; pathogenicity; attenuation; nucleotide sequencing.


Assuntos
Aminoácidos , Infecções por Coronavirus , Vírus da Bronquite Infecciosa , Doenças das Aves Domésticas , Aminoácidos/genética , Animais , Embrião de Galinha , Galinhas , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/virologia , Vírus da Bronquite Infecciosa/classificação , Vírus da Bronquite Infecciosa/genética , Irã (Geográfico) , Doenças das Aves Domésticas/prevenção & controle , Doenças das Aves Domésticas/virologia , Sorogrupo , Vacinas Atenuadas
10.
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
11.
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
12.
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
13.
N Engl J Med ; 381(20): 1897-1908, 2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31722150

RESUMO

BACKGROUND: Many countries have stockpiled vaccines because of concerns about the reemergence of smallpox. Traditional smallpox vaccines are based on replicating vaccinia viruses; these vaccines have considerable side effects. METHODS: To evaluate the efficacy of modified vaccinia Ankara (MVA) as a potential smallpox vaccine, we randomly assigned 440 participants to receive two doses of MVA followed by one dose of the established replicating-vaccinia vaccine ACAM2000 (the MVA group) or to receive one dose of ACAM2000 (the ACAM2000-only group). The two primary end points were noninferiority of the MVA vaccine to ACAM2000 with respect to the peak serum neutralizing antibody titers and attenuation of the ACAM2000-associated major cutaneous reaction by previous MVA vaccination, measured according to the maximum lesion area and the derived area attenuation ratio. RESULTS: A total of 220 and 213 participants were randomly assigned and vaccinated in the MVA group and ACAM2000-only group, respectively, and 208 participants received two MVA vaccinations. At peak visits, MVA vaccination induced a geometric mean titer of neutralizing antibodies of 153.5 at week 6, as compared with 79.3 at week 4 with ACAM2000 (a ratio of 1.94 [95% confidence interval {CI}, 1.56 to 2.40]). At day 14, the geometric mean titer of neutralizing antibodies induced by a single MVA vaccination (16.2) was equal to that induced by ACAM2000 (16.2), and the percentages of participants with seroconversion were similar (90.8% and 91.8%, respectively). The median lesion areas of the major cutaneous reaction were 0 mm2 in the MVA group and 76.0 mm2 in the ACAM2000-only group, resulting in an area attenuation ratio of 97.9% (95% CI, 96.6 to 98.3). There were fewer adverse events or adverse events of grade 3 or higher after both MVA vaccination periods in the MVA group than in the ACAM2000-only group (17 vs. 64 participants with adverse events of grade 3 or higher, P<0.001). CONCLUSIONS: No safety concerns associated with the MVA vaccine were identified. Immune responses and attenuation of the major cutaneous reaction suggest that this MVA vaccine protected against variola infection. (Funded by the Office of the Assistant Secretary for Preparedness and Response Biomedical Advanced Research and Development Authority of the Department of Health and Human Services and Bavarian Nordic; ClinicalTrials.gov number, NCT01913353.).


Assuntos
Anticorpos Antivirais/sangue , Vacina Antivariólica/imunologia , Varíola/prevenção & controle , Vírus Vaccinia/imunologia , Adolescente , Adulto , Anticorpos Neutralizantes/sangue , Feminino , Humanos , Masculino , Varíola/imunologia , Vacina Antivariólica/efeitos adversos , Resultado do Tratamento , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/imunologia , Adulto Jovem
14.
PLoS Negl Trop Dis ; 13(11): e0007800, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31725816

RESUMO

B cell activating factor (BAFF) is a member of the tumor necrosis factor (TNF) superfamily of cytokines that links innate with adaptive immunity. BAFF signals through receptors on B cells, making it an attractive molecule to potentiate vaccine-induced B cell responses. We hypothesized that a rabies virus (RABV)-based vaccine displaying both antigen and BAFF on the surface of the same virus particle would target antigen-specific B cells for activation and improve RABV-specific antibody responses. To test this hypothesis, we constructed a recombinant RABV-based vector expressing virus membrane-anchored murine BAFF (RABV-ED51-mBAFF). BAFF was incorporated into the RABV particle and determined to be biologically functional, as demonstrated by increased B cell survival of primary murine B cells treated ex-vivo with RABV-ED51-mBAFF. B cell survival was inhibited by pre-treating RABV-ED51-mBAFF with an antibody that blocks BAFF functions. RABV-ED51-mBAFF also activated primary murine B cells ex-vivo more effectively than RABV as shown by significant upregulation of CD69, CD40, and MHCII on the surface of infected B cells. In-vivo, RABV-ED51-mBAFF induced significantly faster and higher virus neutralizing antibody (VNA) titers than RABV while not adversely affecting the longevity of the vaccine-induced antibody response. Since BAFF was incorporated into the virus particle and genome replication was not required for BAFF expression in-vivo, we hypothesized that RABV-ED51-mBAFF would be effective as an inactivated vaccine. Mice immunized with 250 ng/mouse of ß-propriolactone-inactivated RABV-ED51-mBAFF showed faster and higher anti-RABV VNA titers compared to mice immunized with inactivated RABV. Together, this model stands as a potential foundation for exploring other virus membrane-anchored molecular adjuvants to make safer, more effective inactivated RABV-based vaccines.


Assuntos
Formação de Anticorpos/imunologia , Fator Ativador de Células B/imunologia , Linfócitos B/imunologia , Vacinas Antirrábicas/imunologia , Raiva/imunologia , Raiva/prevenção & controle , Vírion/imunologia , Adjuvantes Imunológicos , Animais , Anticorpos Antivirais/sangue , Citocinas/metabolismo , Feminino , Imunização , Cinética , Camundongos , Camundongos Endogâmicos C57BL , Vacinas Antirrábicas/efeitos adversos , Vírus da Raiva/genética , Vírus da Raiva/crescimento & desenvolvimento , Vírus da Raiva/imunologia , Vacinação , Vacinas Atenuadas/imunologia , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Vacinas Sintéticas
16.
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
17.
Vet Microbiol ; 239: 108492, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31767065

RESUMO

Swine influenza A virus (IAV-S) infections are a major cause of economic losses for the swine industry. The vast genetic and antigenic diversity often results in mismatch between the vaccine and field strains, necessitating frequent updates of vaccines. Inactivated IAV-S vaccines are of questionable efficacy. Intra-nasally administered live vaccines are more effective but are associated with safety concerns. The objective of this study was to develop a first-generation vaccine which combines the safety and efficacy advantages of inactivated and attenuated vaccines respectively. The approach targeted fragmentation of viral nucleic acids while preserving structure. Hence, cultures of influenza A/CA/04/09 H1N1 were exposed to 44 °C for 10 min. to reversibly denature the capsid, followed by RNase treatment to digest the genomic RNA and then refolded at lower temperatures. As targeted, treated virions retained an intact structure and were not detected in the first passage in infected cells. To improve intra-nasal delivery of the vaccine antigen, the vaccine antigen was delivered in porcine lung surfactant. Both the treated vaccine alone or vaccine in combination with the surfactant elicited strong anti-HA and virus neutralizing antibodies, protection against viral shedding and lung lesions in 3-week-old piglets. There were no significant differences between the groups. Vaccine viral replication was not detected in the vaccinated pigs. The described approach can advance current immunization practices against swine influenza viruses due to the relative simplicity, high efficacy and safety and ease of adaptation to newly emerging field strains.


Assuntos
Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/veterinária , Tensoativos/administração & dosagem , Vacinas Atenuadas/imunologia , Vacinas de Produtos Inativados/imunologia , Administração Intranasal/veterinária , Animais , Anticorpos Antivirais/sangue , Temperatura Alta , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Suínos , Doenças dos Suínos/prevenção & controle , Doenças dos Suínos/virologia , Vacinas Atenuadas/administração & dosagem , Vacinas de Produtos Inativados/administração & dosagem
18.
Vet Microbiol ; 239: 108488, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31767066

RESUMO

Acriflavine, an acridine dye that causes frameshift mutations, has been used to attenuate various veterinary pathogens for the development of live vaccines. Erysipelothrix rhusiopathiae Koganei 65-0.15 strain (Koganei) (serovar 1a) is the acriflavine-resistant live vaccine currently used in Japan for the control of swine erysipelas. To investigate the attenuation mechanisms of the Koganei strain, we analyzed the draft genome sequence of the Koganei strain against the reference genome sequence of the E. rhusiopathiae Fujisawa strain (serovar 1a). The sequence analysis revealed a high degree of sequence similarity between the two strains and identified a total of 98 sequence differences within 80 protein-coding sequences. Among them, insertions/deletions (indels) were identified in 9 genes, of which 7 resulted in frameshift and premature termination. To investigate whether these mutations resulted in the attenuation of the Koganei strain, we focused on the indel mutation identified in ERH_0661, an XRE family transcriptional regulator. We introduced the mutation into ERH_0661 of the Fujisawa strain and restored the mutation of the Koganei strain. Animal experiments using the recombinant strains showed that mice survived inoculation with 103 colony forming units (CFUs) (equivalent to approximately 100 50% lethal doses [LD50] of the wild-type Fujisawa) of the recombinant Fujisawa strain, and the mice became ill after inoculation with 108 CFUs of the recombinant Koganei strain. These results suggest that the transcriptional regulator ERH_0661 is involved in the virulence of E. rhusiopathiae and that the ERH_0661 mutation is partially responsible for the attenuation of the Koganei strain.


Assuntos
Erysipelothrix/genética , Vacinas Atenuadas/genética , Virulência/genética , Acriflavina/farmacologia , Animais , Sequência de Bases , DNA Bacteriano/efeitos dos fármacos , DNA Bacteriano/genética , Erysipelothrix/patogenicidade , Feminino , Genoma Bacteriano/genética , Camundongos , Mutação , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Especificidade da Espécie , Virulência/efeitos dos fármacos
19.
Vet Microbiol ; 239: 108497, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31767085

RESUMO

The objective of this study was to evaluate the effect of concurrent vaccination with a porcine reproductive and respiratory syndrome virus (PRRSV)-1 modified-live virus (MLV) vaccine and a PRRSV-2 MLV vaccine against a dual heterologous PRRSV-1 and PRRSV-2 challenge in late term pregnancy gilts. Gilts were concurrently administered PRRSV-1 and PRRSV-2 MLV vaccines at 21 days prior to breeding at separate anatomical sites and were inoculated intranasally with both PRRSV types at 93 days of gestation. Vaccinated gilts had a higher number of live-born and weaned pigs, and a decrease in stillbirths compared to the unvaccinated control group following a dual challenge. Concurrent vaccination resulted also in the reduction of both PRRSV-1 and PRRSV-2 viremia which correlated with an increase in the number of PRRSV-1 and PRRSV-2 specific interferon-γ secreting cells (IFN-γ-SC). We believe the T cell responses contributed to the reduction of both PRRSV-1 and PRRSV-2 viremia. The results presented here demonstrate that concurrent vaccination with PRRSV-1 and PRRSV-2 MLV vaccines improves reproductive performance, reduces viremia of PRRSV-1 and PRRSV-2, and induces protective T cell reactions against dual PRRSV-1 and PRRSV-2 challenge in late term pregnancy gilts without local and systemic adverse reactions related to concurrent vaccination.


Assuntos
Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Vírus da Síndrome Respiratória e Reprodutiva Suína/imunologia , Vacinação/veterinária , Vacinas Atenuadas/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Feminino , Gravidez , Resultado da Gravidez/veterinária , Suínos , Vacinação/normas , Viremia/prevenção & controle , Viremia/veterinária
20.
Vet Microbiol ; 239: 108447, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31767087

RESUMO

Brucellosis is one of the most common zoonotic diseases worldwide. Almost 500,000 new human cases occur each year; yet there is no vaccine for human use. Moreover, there is no universal Brucella vaccine that would provide protection against all pathogenic species of Brucella. We generated a rough, live-attenuated B. neotomae strain by deleting the wboA gene encoding a glycosyltransferase. This strain lacks the O-side chain in its lipopolysaccharide (LPS) and thus the vaccinated animals can be differentiated serologically from the field-infected animals. We tested the efficacy of rough B. neotomae strain to stimulate dendritic cells compared to the smooth wild type strain. Based on TNF-α production, our data suggests that a significantly higher stimulation was obtained when dendritic cells were stimulated with the rough vaccine strain compared to the smooth wild type B. neotomae. Furthermore, the rough mutant was cleared from mice within 6 weeks even at a dose as high as 2 x 108 CFU. Vaccinated mice showed significantly higher level of protection against a virulent B. suis 1330 challenge compared to the control mice. Antibody titers in the mice and cytokine production by the splenocytes from the vaccinated mice showed a Th1 mediated immune response that correlated with the protection.


Assuntos
Vacina contra Brucelose/imunologia , Brucella/imunologia , Brucelose/prevenção & controle , Animais , Anticorpos Antibacterianos/sangue , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Brucella/genética , Vacina contra Brucelose/normas , Brucella suis , Brucelose/imunologia , Brucelose/microbiologia , Deleção de Genes , Camundongos , Vacinas Atenuadas/imunologia
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