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1.
Vet Immunol Immunopathol ; 213: 109887, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307668

RESUMO

Chlamydia abortus produces ovine enzootic abortion (OEA). Symptoms are not observed until the organism colonises the placenta, eventually causing abortion. Infected animals become carriers and will shed the organism in the following oestruses. This process suggests that sex hormones might play an important role in the physiopathology of OEA, affecting the success of chlamydial clearance and also jeopardising the effectiveness of vaccination. However, the mechanisms through which sex hormones are involved in chlamydial pathogenicity remain unclear. The aim of this study, therefore, was to determine the effect of progesterone on the immune response against C. abortus and on the protection conferred by an experimental inactivated vaccine in sheep. Eighteen sheep were ovariectomised and divided into four groups: vaccinated and progesterone-treated (V-PG), vaccinated and non-treated (V-NT), non-vaccinated and non-treated (NV-NT) and non-vaccinated and progesterone-treated sheep (NV-PG). Animals from both PG groups were treated with commercial medroxyprogesterone acetate impregnated intravaginal sponges before and during the vaccination (V-PG) or just before challenge (NV-PG). The animals from both V groups were subcutaneously immunised with an experimental inactivated vaccine, which was seen to confer high protection in previous studies. All sheep were challenged intratracheally with C. abortus strain AB7 and were sacrificed on day 8 post-infection. Morbidity was measured as the variation in rectal temperature and samples of sera were collected for antibody and cytokine (IFN-γ and IL-10) analysis by commercial ELISA. In addition, lung and lymph node samples were collected for chlamydial detection by qPCR and for histopathological and immunohistochemical analyses. Sheep from the V-PG group showed less severe or no lesions and lower morbidity than the other groups. They also had the highest abundance of regulatory T-cells. The sheep from V-NT also manifested high antibody levels against C. abortus and less severe lesions than those observed in non-vaccinated sheep, which showed high morbidity, low antibody levels and severe lesions, especially in NV-NT. These results confirm the effectiveness of the experimental vaccine employed and suggest that progesterone could enhance the effect.


Assuntos
Vacinas Bacterianas/uso terapêutico , Infecções por Chlamydia/veterinária , Imunidade Humoral , Progesterona/administração & dosagem , Doenças dos Ovinos/imunologia , Aborto Animal/imunologia , Aborto Animal/prevenção & controle , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/imunologia , Chlamydia/imunologia , Infecções por Chlamydia/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Ovinos , Doenças dos Ovinos/microbiologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico
2.
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
3.
J Fish Dis ; 42(7): 1057-1064, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31087342

RESUMO

Lumpfish (Cyclopterus lumpus), a native fish of the North Atlantic Ocean, is utilized as cleaner fish to biocontrol sea lice infestations in Atlantic salmon aquaculture. However, bacterial infections are affecting cleaner fish performance. Vibrio anguillarum, the aetiological agent of vibriosis, is one of the most frequent bacterial infections in lumpfish, and effective vaccine programmes against this pathogen have been identified as a high priority for lumpfish. Vibrogen-2 is a commercial polyvalent bath vaccine that contains formalin-inactivated cultures of V. anguillarum serotypes O1 and O2, and Vibrio ordalii. In this study, we evaluated Vibrogen-2 efficacy in lumpfish against a local isolated V. anguillarum strain. Two groups of 125 lumpfish were bath-immunized, bath-boost-immunized at four weeks post-primary immunization, and intraperitoneally (i.p.) boost-immunized at eight weeks post-primary immunization. The control groups were i.p. mock-immunized with PBS. Twenty-seven weeks post-primary immunization, the fish were i.p. challenged with 10 or 100 times the V. anguillarum J360 LD50 dose. After the challenge, survival was monitored daily, and samples of tissues were collected at ten days post-challenge. Commercial vaccine Vibrogen-2 reduced V. anguillarum tissue colonization and delayed mortality but did not confer immune protection to C. lumpus against the V. anguillarum i.p. challenge.


Assuntos
Vacinas Bacterianas/uso terapêutico , Doenças dos Peixes/prevenção & controle , Peixes/microbiologia , Vibrioses/veterinária , Vibrio/imunologia , Animais , Aquicultura , Vacinas Bacterianas/imunologia , Agentes de Controle Biológico , Doenças dos Peixes/imunologia , Imersão , Dose Letal Mediana , Vacinação/métodos , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico , Vibrioses/imunologia , Vibrioses/prevenção & controle
4.
Arch Virol ; 164(6): 1501-1513, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30888563

RESUMO

Foot-and-mouth disease (FMD) is a major worldwide viral disease in animals, affecting the national and international trade of livestock and animal products and leading to high economic losses and social consequences. Effective control measures of FMD involve prevention through vaccination with inactivated vaccines. These inactivated vaccines, unfortunately, require short-term protection and cold-chain and high-containment facilities. Major advances and pursuit of hot topics in vaccinology and vectorology are ongoing, involving peptide vaccines, DNA vaccines, live vector vaccines, and novel attenuated vaccines. DIVA capability and marker vaccines are very important in differentiating infected animals from vaccinated animals. This review focuses on updating the research progress of these novel vaccines, summarizing their merits and including ideas for improvement.


Assuntos
Vírus da Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Gado/virologia , Vacinas Virais/uso terapêutico , Animais , Bovinos , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/virologia , Febre Aftosa/imunologia , Vírus da Febre Aftosa/genética , Doenças dos Cavalos/prevenção & controle , Doenças dos Cavalos/virologia , Cavalos , Ovinos , Doenças dos Ovinos/prevenção & controle , Doenças dos Ovinos/virologia , Vacinas de DNA/imunologia , Vacinas de DNA/uso terapêutico , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico , Vacinas de Subunidades/imunologia , Vacinas de Subunidades/uso terapêutico , Vacinas de Partículas Semelhantes a Vírus/uso terapêutico , Vacinas Virais/imunologia
5.
Biochem Biophys Res Commun ; 511(2): 253-259, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30777330

RESUMO

Inactivated vaccines are widely used for prevention of viral disease. Both humoral and cellular immune responses have been shown to play important roles in the control and clearance of virus infections. CpG motif containing oligodeoxynucleotides (ODN) have recently gained considerable interest and been used as vaccine adjuvant due to their potent abilities to modulate host immune response. In this study, CpG-ODN adjuvant and inactivated viral particles of enterovirus 71 (EV71) were co-encapsulated into nanoparticles (NP) generated by using protamine sulfate (PS) and carboxymethyl ß-glucan (CMG) through a self-assembly approach. The administration of EV71 nanovaccine elicited not only specific anti-EV71 neutralizing antibody response, but also cellular immune response characterized by strong productions of IFN-α and IFN-γ. The results suggest that CMG/PS-based nanovehicles hold a great potential to be a novel platform for nanovaccine development against viral disease.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Enterovirus Humano A/imunologia , Infecções por Enterovirus/prevenção & controle , Oligodesoxirribonucleotídeos/administração & dosagem , Vacinas de Produtos Inativados/administração & dosagem , Vacinas Virais/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Animais , Infecções por Enterovirus/imunologia , Infecções por Enterovirus/virologia , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nanopartículas/química , Oligodesoxirribonucleotídeos/uso terapêutico , Protaminas/química , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico , Vacinas Virais/imunologia , Vacinas Virais/uso terapêutico , beta-Glucanas/química
6.
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
7.
Fish Shellfish Immunol ; 86: 635-640, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30528659

RESUMO

Vaccination is the most effective approach for prevention of infectious diseases in aquaculture. Although immersion vaccination is more applicable compared to in-feed/oral administration and injection, this method suffers from low potency as the efficiency of uptake of antigens through mucosal membranes is limited. In this study, we have successfully developed a mucoadhesive vaccine delivery system to enhance the efficacy of direct immersion vaccination against Flavobacterium columnare, the causative agent of columnaris disease in red tilapia. A formalin-killed negatively charged, bacterial cell suspension was used to prepare a mucoadhesive vaccine by electrostatic coating with positively charged chitosan. Our results demonstrate that the chitosan-complexed vaccine greatly increases its mucoadhesiveness, thus increasing the chances of vaccine uptake by the gill mucosa and improving the protection obtained against columnaris infection. The surface charge of the chitosan-complexed vaccine was altered from anionic to cationic after chitosan modification. Tilapia were vaccinated with the prepared chitosan-complexed vaccine by immersion. The challenge test was then carried out 30 and 60 days post vaccination, which resulted in a high level of mortalities in the non-vaccinated and uncomplexed vaccine groups. A high relative percentage survival (RPS) of vaccinated fish was noted with the mucoadhesive vaccine. Our results indicated that the naked vaccine failed to protect the fish from columnaris infection, which is consistent with the mucoadhesive assays performed during the study showing that the naked vaccine was unable to bind to mucosal surfaces. This system is therefore an effective method for immersion vaccination in order to deliver the antigen preparation to the mucosal surface membrane of the fish.


Assuntos
Vacinas Bacterianas/uso terapêutico , Doenças dos Peixes/prevenção & controle , Infecções por Flavobacteriaceae/veterinária , Polímeros/química , Tilápia/imunologia , Vacinação/métodos , Adesivos/química , Animais , Aquicultura , Vacinas Bacterianas/química , Quitosana/química , Infecções por Flavobacteriaceae/prevenção & controle , Flavobacterium , Brânquias/imunologia , Imersão , Membrana Mucosa/metabolismo , Eletricidade Estática , Propriedades de Superfície , Tilápia/microbiologia , Vacinas de Produtos Inativados/química , Vacinas de Produtos Inativados/uso terapêutico
8.
Vaccine ; 37(3): 452-457, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30554797

RESUMO

Traditionally, immune response to influenza vaccines has been measured using the haemagglutination inhibition (HAI) assay. A broader repertoire of techniques including the sensitive viral microneutralization (VMN) assay is now recommended by the European Medicines Agency (EMA). Comparing HAI and VMN, we determined immune response to a trivalent 2015-2016 seasonal inactivated influenza vaccine (SIIV) administered to 28 recipients of allogeneic haematopoietic stem cell transplant (HSCT). Vaccination was within the first-year post-transplant at a median of 78.5 (24-363) days. The proportion of patients with baseline and post-vaccination HAI titres ≥ 1:40 were 28.6% and 25% for A(H1N1)pdm09, 14.3% at both timepoints for A(H3N2), and 32.1% and 25% for B(Phuket). Pre and Post-vaccination geometric mean titres(GMT) were higher by VMN than HAI for A(H1N1)pdm09 and A(H3N2), but lower for B(Phuket)(p=<0.05). Geometric mean ratios(GMR) of baseline and post-vaccination titres were similar by HAI and VMN(p > 0.05) for all components. A single seroconversion to A(H1N1) was detected by ELISA-VMN. None of patient age, lymphocyte count, days from transplant to vaccination, donor type, or graft-versus-host disease (GVHD) or immunosuppressive therapy (IST) at vaccination correlated with baseline or post-vaccination titres by either assay. This absence of seroresponse to SIIV in the first-year post HSCT highlights the need for novel immunogenic vaccination formulations and schedules in this high-risk population.


Assuntos
Anticorpos Antivirais/sangue , Testes de Inibição da Hemaglutinação/normas , Transplante de Células-Tronco Hematopoéticas , Imunogenicidade da Vacina , Vacinas contra Influenza/imunologia , Testes de Neutralização/normas , Adulto , Idoso , Feminino , Humanos , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza B , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Vacinação , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico
9.
Expert Opin Biol Ther ; 18(12): 1247-1256, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30426788

RESUMO

INTRODUCTION: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection in infants and elderly and to date, there is no safe or effective vaccine against RSV. AREAS COVERED: This review provides a roadmap to RSV vaccine development. It is a journey spanning over more than half a century from the initial disappointment with inactivated formalin vaccine to the current advancements in vaccine technology. We highlight the important aspects of RSV structural biology and protective immune response. We include discussion of newer fusion glycoprotein immune targets and current vaccine candidates. We used Pub Med and Medline resources for literature search. EXPERT OPINION: A resurgence of information on the burden related to RSV infection coupled with the newer understanding of the molecular mechanism of RSV infection has reignited a tremendous activity in RSV vaccine discovery. The vaccine pipeline is diverse and target populations are varied, thus making the goal of a safe and effective RSV vaccine in the future within reach.


Assuntos
Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Vírus Sincicial Respiratório/uso terapêutico , Vacinação , Idoso , Idoso de 80 Anos ou mais , Animais , Humanos , Recém-Nascido , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sincicial Respiratório Humano/imunologia , Vacinação/métodos , Vacinação/tendências , Vacinas de Produtos Inativados/uso terapêutico
10.
Vaccine ; 36(41): 6087-6094, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30195486

RESUMO

BACKGROUND: Standard influenza vaccines may be of limited benefit to patients with end-stage renal disease (ESRD). These patients may benefit from high-dose influenza vaccine, currently indicated for patients aged ≥65 years. Studies in other populations have demonstrated that high-dose vaccine elicits a stronger immunological response. We compared vaccine uptake in the United States and predictors of receipt for high-dose and standard influenza vaccines. METHODS: Using data from the United States Renal Data System (2010-2013), we conducted a cohort study of 421,482 adult patients on hemodialysis. We examined temporal trends in uptake of high-dose or standard trivalent influenza vaccine each influenza season, and used multivariate logistic regression to assess the association between individual-level variables (e.g., demographics, comorbidities) and facility-level variables (e.g., facility size and type) with vaccine receipt. RESULTS: The proportion of patients with ESRD who were vaccinated with any influenza vaccine increased from 68.3% in 2010 to 72.4% in 2013. High-dose vaccines were administered to 0.9% of patients during the study period, and 16.7% of high-dose vaccines were administered to patients <65 years of age. Among patients aged ≥65 years, older patients (>79 vs. 65-69 years: OR, 1.29; 95% CI, 1.19-1.41) and patients at hospital-based versus free-standing dialysis facilities (OR, 2.31; 95% CI, 2.13-2.45) were more likely to receive high-dose vaccine, while blacks (vs. whites [OR, 0.66; 95% CI, 0.61-0.71]) and patients with longer duration of ESRD (>9 vs. 0 years: OR, 0.66; 95% CI, 0.55-0.78) were less likely to receive the high-dose vaccine. CONCLUSIONS: While the overall influenza vaccination rate has increased, use of high-dose vaccine among patients with ESRD was very low. Being an older patient, living in the Midwest, and receiving care at hospital-based facilities were the strongest predictors of receiving high-dose vaccine.


Assuntos
Vacinas contra Influenza/uso terapêutico , Diálise Renal , Idoso , Feminino , Humanos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Falência Renal Crônica/terapia , Masculino , Estados Unidos , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico
11.
Vaccine ; 36(41): 6103-6110, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30181048

RESUMO

Influenza A virus (IAV) causes a disease burden in the swine industry in the US and is a challenge to prevent due to substantial genetic and antigenic diversity of IAV that circulate in pig populations. Whole inactivated virus (WIV) vaccines formulated with oil-in-water (OW) adjuvant are commonly used in swine. However, WIV-OW are associated with vaccine-associated enhanced respiratory disease (VAERD) when the hemagglutinin and neuraminidase of the vaccine strain are mismatched with the challenge virus. Here, we assessed if different types of adjuvant in WIV vaccine formulations impacted VAERD outcome. WIV vaccines with a swine δ1-H1N2 were formulated with different commercial adjuvants: OW1, OW2, nano-emulsion squalene-based (NE) and gel polymer (GP). Pigs were vaccinated twice by the intramuscular route, 3 weeks apart, then challenged with an H1N1pdm09 three weeks post-boost and necropsied at 5 days post infection. All WIV vaccines elicited antibodies detected using the hemagglutination inhibition (HI) assay against the homologous vaccine virus, but not against the heterologous challenge virus; in contrast, all vaccinated groups had cross-reactive IgG antibody and IFN-γ responses against H1N1pdm09, with a higher magnitude observed in OW groups. Both OW groups demonstrated robust homologous HI titers and cross-reactivity against heterologous H1 viruses in the same genetic lineage. However, both OW groups had severe immunopathology consistent with VAERD after challenge when compared to NE, GP, and non-vaccinated challenge controls. None of the WIV formulations protected pigs from heterologous virus replication in the lungs or nasal cavity. Thus, although the type of adjuvant in the WIV formulation played a significant role in the magnitude of immune response to homologous and antigenically similar H1, none tested here increased the breadth of protection against the antigenically-distinct challenge virus, and some impacted immunopathology after challenge.


Assuntos
Vacinas contra Influenza/uso terapêutico , Doenças Respiratórias/prevenção & controle , Vacinas de Produtos Inativados/uso terapêutico , Animais , Ensaio de Imunoadsorção Enzimática , Pulmão/metabolismo , Pulmão/virologia , Neuraminidase/antagonistas & inibidores , Doenças Respiratórias/imunologia , Suínos
12.
Vaccine ; 36(43): 6449-6455, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30243500

RESUMO

Influenza becomes epidemic worldwide every year, and many individuals receive vaccination annually. Quality control relating to safety and potency of influenza vaccines is important to maintain public confidence. The safety of influenza vaccines has been assessed by clinical trials, and animal safety tests are performed to monitor the consistent quality between vaccines used for clinical trials and marketing; the biological responses in vaccinated animals are evaluated, including changes in body weight and white blood cell count. Animal safety tests have been contributing to the quality relating to the safety of influenza vaccines for decades, but improvements are needed. Although precise mechanisms involving biological changes in animal safety tests have not been fully elucidated, the application of cDNA microarray technology make it possible to reliably identify genes related to biological responses in vaccinated animals. From analysis of the expression profile of >10,000 genes of lung in animals treated with an inactivated whole virion influenza vaccine, we identified 17 marker genes whose expression patterns correlated well to changes in body weight and leukocyte count in vaccinated animals. In influenza HA vaccine-treated animals exhibiting subtle changes in biological responses, a robust expression pattern of marker genes was found. Furthermore, these marker genes could also be used in the evaluation of adjuvanted influenza vaccines. The expression profile of marker genes is expected to be an alternative indicator for safety control of various influenza vaccines conferring high sensitivity and short turnaround time. Thus, gene expression profiling may be a powerful tool for safety control of vaccines in the future.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Perfilação da Expressão Gênica , Vacinas contra Influenza/uso terapêutico , Infecções por Orthomyxoviridae/genética , Animais , Anticorpos Antivirais/sangue , Biomarcadores/análise , Peso Corporal , Cobaias , Virus da Influenza A Subtipo H5N1 , Vacinas contra Influenza/efeitos adversos , Japão , Análise em Microsséries , Controle de Qualidade , Ratos , Testes de Toxicidade , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/uso terapêutico
13.
J Aquat Anim Health ; 30(4): 312-324, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30120830

RESUMO

No vaccine is yet commercially available against Mycobacterium marinum, the etiological agent of fish mycobacteriosis (also known as "fish tuberculosis"). The mycobacterial gene responsible for invasion and intracellular persistence, iipA, is known to moderate M. marinum pathology in Zebrafish Danio rerio. Two doses of heat-killed, wild-type, virulent M. marinum and two doses of a heat-killed, avirulent M. marinum iipA::kan mutant strain were used in parallel to vaccinate European Seabass Dicentrarchus labrax. The fish were then challenged with live, virulent M. marinum, and the pathogenesis of the infection was monitored. High specific immunoglobulin M (IgM) response and an increase in cytokine tumor necrosis factor alpha (TNF-α) messenger RNA expression levels were observed in all vaccinated fish. At 1 month postchallenge, TNF-α expression levels increased in spleen tissues of fish vaccinated with the virulent type and in those of unvaccinated fish, whereas in the head kidney, expression was up-regulated only in unvaccinated fish. The expression then decreased, and at 2 months postchallenge, expression appeared similar in all vaccination types. The highest survival rate (75%) was recorded in the group of fish that were vaccinated with a high dose of avirulent iipA::kan mutant. The iipA::kan mutant induced a strong immune response accompanied by only modest tissue disruption. Coupled with an effective program of booster treatments, the iipA::kan mutant vaccine may be developed into a powerful preventive measure against fish mycobacteriosis.


Assuntos
Doenças dos Peixes/microbiologia , Infecções por Micobactéria não Tuberculosa/veterinária , Mycobacterium marinum/patogenicidade , Animais , Bass , Doenças dos Peixes/imunologia , Temperatura Alta , Imunidade Celular , Imunidade Humoral , Imunoglobulina M/metabolismo , Infecções por Micobactéria não Tuberculosa/imunologia , Mycobacterium marinum/genética , Mycobacterium marinum/imunologia , RNA Mensageiro , Fator de Necrose Tumoral alfa/metabolismo , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico
14.
Vaccine ; 36(37): 5510-5518, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-30093289

RESUMO

OBJECTIVES: We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) in children 6 months to 15 years of age during the 2016/17 season. In addition, we estimated the impact of repeated vaccination in children on VE. METHODS: Our study for VEs in preventing influenza and admission due to influenza were conducted according to a test-negative case-control design (TNCC) based on influenza rapid diagnostic test results. We also analyzed the VE by vaccine status in the current and previous seasons for the impact of repeated vaccination. RESULTS: During the 2016/17 season, the quadrivalent IIV was used in Japan. The adjusted VE in preventing influenza illness was 38% (95% CI, 29-46) against influenza A and 39% (95% CI, 18-54) against influenza B. Infants showed no significant VE. The VE in preventing hospitalization was not demonstrated. For the analysis of repeated vaccination, the vaccine was effective only when immunization occurred in the current season. The children who were immunized in two consecutive seasons were more likely to develop influenza compared to those immunized in the current season only (odds ratio, 1.58 [95% CI, 1.05-2.38], adjusted odds ratio, 1.53 [95% CI, 0.99-2.35]). However, the odds ratio of repeated vaccination was not significant when the analysis excluded those who developed influenza in the previous season. CONCLUSIONS: VE in children in the 2016/17 season was similar to values previously reported. Repeated vaccination interfered with the VE against any influenza infection in the 2016/17 season. The results of our study suggest that decreased VE by repeat vaccination phenomenon was associated with immunity by influenza infection in the previous season. However, the influenza vaccine should be recommended every season for children.


Assuntos
Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza B , Masculino , Razão de Chances , Estações do Ano , Vacinação , Vacinas de Produtos Inativados/uso terapêutico
15.
Vaccine ; 36(35): 5318-5324, 2018 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-30054161

RESUMO

This study aimed to investigate the chemokine CCL20, a macrophage inflammatory protein-3 alpha, for adjuvant potential in inactivated foot-and-mouth disease (FMD) vaccine. Groups of mice were injected intramuscularly with either murine CCL20 DNA or CCL20 protein two days ahead of the immunization with Montanide ISA206 adjuvanted inactivated FMD vaccine and humoral and cellular immune responses were measured in post-vaccinal sera. We demonstrated that the mice immunized with CCL20 plasmid plus FMD vaccine showed earlier and significantly (p < 0.05) higher neutralizing antibody responses compared to the mice vaccinated with CCL20 protein plus FMD vaccine. In fact, CCL20 as a protein did not show any adjuvant effect and the immune responses induced in this group were comparable to that of the mice vaccinated with FMD vaccine alone. All the vaccination groups showed serum IgG1 and IgG2 antibody responses; however, the mice vaccinated with CCL20 plasmid plus FMD vaccine showed significantly (p < 0.05) higher IgG1 and IgG2 responses and the responses remained high at all-time points post vaccination, although not always statistically significant. Upon restimulation of the vaccinated splenocytes with the inactivated FMD viral antigen, significantly (p < 0.05) higher IFN-γ and IL-2 levels in culture supernatants were found in animals vaccinated with the CCL20 plasmid plus FMD vaccine, which is indicative of the TH1 type of cellular immunity. On challenge with the homologous FMD virus on 28th day post immunization, CCL20 plasmid plus FMD vaccine showed complete protection (100%) while animals immunized with CCL20 protein plus FMD vaccine or FMD vaccine alone showed 66% protection. In summary, we show that prior injection of CCL20 plasmid improved protective efficacy of the inactivated FMD vaccine and thus offers a valuable strategy to modulate the efficacy and polarization of specific immunity against inactivated vaccines.


Assuntos
Quimiocina CCL20/metabolismo , Vírus da Febre Aftosa/imunologia , Vírus da Febre Aftosa/patogenicidade , Febre Aftosa/prevenção & controle , Plasmídeos/genética , Animais , Anticorpos Neutralizantes/imunologia , Quimiocina CCL20/genética , Feminino , Febre Aftosa/imunologia , Camundongos , Vacinas de Produtos Inativados/uso terapêutico
16.
Vaccine ; 36(33): 5002-5009, 2018 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-30017147

RESUMO

Outbreaks of viral nervous necrosis (VNN) in Asian sea bass (Lates calcarifer) at the larval stages via vertical transmission of nervous necrosis virus (NNV) from asymptomatic broodfish remain as a major deterrent during seed production. A five-year study was conducted to produce NNV-specific-free sea bass broodfish reared in land-based tanks through an annual immunization regimen with the formalin-inactivated NNV. We primarily immunized (intraperitoneal injection) sea bass juveniles (5 g) and monitored the neutralizing antibody (Nab) titers in the sera of these fish at scheduled intervals post-immunization. Nab titers in the sera of immunized fish peaked at Month 2 (titer: 1:4480 ±â€¯1185) but thereafter gradually declined and significantly dropped (1:260 ±â€¯83) at Month 12 post-primary immunization. Booster immunization of these fish at Month 12 post-immunization led to abrupt increases in Nab titers in booster immunized (B-Im) fish at Month 1 (1:12800 ±â€¯6704) but thereafter declined and dropped at Month 12 (1:480 ±â€¯165) post-booster immunization. The annual booster injections with the inactivated vaccine or L-15 (Unimmunized [U-Im]) were consecutively conducted for 4 years until the fish became sexually mature. Mature fish from both groups were successively induced to spawn twice (1-month interval) via intramuscular injection with luteinizing hormone-releasing hormone analogue (LHRH-a; 100 µg/kg BW). NNV was not detected by RT-PCR in oocytes and milts, and spawned eggs of B-Im fish. In contrast, oocytes and milts, and spawned eggs of U-Im fish were NNV positive. Spawned eggs of B-Im broodfish exhibited Nab titers ranging from 1:192 ±â€¯34 to 1:240 while such was not detected (<1:40) in eggs of U-Im fish. Taken together, current data clearly demonstrate that annual immunization regimen with inactivated NNV vaccine is a pragmatic approach for sustaining immunocompetent sea bass broodfish reared in land-based tanks and circumvent the risk of vertical transmission of NNV from asymptomatic broodfish to their offspring under stress of repetitive spawning.


Assuntos
Bass/virologia , Nodaviridae/patogenicidade , Perciformes/virologia , Infecções por Vírus de RNA/transmissão , Animais , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/metabolismo , Bass/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/prevenção & controle , Doenças dos Peixes/virologia , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Perciformes/imunologia , Infecções por Vírus de RNA/virologia , Vacinas de Produtos Inativados/uso terapêutico
17.
Vaccine ; 36(30): 4447-4453, 2018 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-29935860

RESUMO

BACKGROUND: Mycobacterial infections greatly affect human and animal health worldwide, and vaccines are effective, sustainable and economic interventions for the prevention and control of these infectious diseases. Recent results support the use of zebrafish as a model for studying the pathophysiology of mycobacterial infection and for the development of novel interventions for tuberculosis (TB) control. Recently, we showed that oral immunization with the heat-inactivated M. bovis vaccine (M. bovis IV) protect wild boar against TB, and suggested that this vaccine may controls mycobacterial infection in other species. METHODS: In this study we evaluated the effect of M. bovis IV on the control of mycobacteriosis in zebrafish mucosally vaccinated by immersion and challenged intraperitoneally with Mycobacterium marinum. RESULTS: The results showed that the M. bovis IV administered by immersion protected zebrafish against mycobacteriosis caused by M. marinum by reduction in mycobacterial infection, the number of mycobacteria per granuloma and the number of granulomas per fish. An IgM antibody response against M. bovis antigens was developed in vaccinated fish. Evidences suggested that the protective mechanism elicited by mucosal vaccination with M. bovis IV in zebrafish was based on the activation of the innate immune response through the C3 pathway. CONCLUSIONS: These results support the use of the M. bovis IV administered by immersion for the control of mycobacteriosis in fish.


Assuntos
Mycobacterium bovis/patogenicidade , Animais , Temperatura Alta , Imunidade Inata/imunologia , Imunidade Inata/fisiologia , Membrana Mucosa/imunologia , Mycobacterium bovis/imunologia , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose/prevenção & controle , Vacinas contra a Tuberculose/uso terapêutico , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico , Peixe-Zebra
18.
Cochrane Database Syst Rev ; 6: CD002733, 2018 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-29943802

RESUMO

BACKGROUND: Influenza vaccinations are currently recommended in the care of people with COPD, but these recommendations are based largely on evidence from observational studies, with very few randomised controlled trials (RCTs) reported. Influenza infection causes excess morbidity and mortality in people with COPD, but there is also the potential for influenza vaccination to cause adverse effects, or not to be cost effective. OBJECTIVES: To determine whether influenza vaccination in people with COPD reduces respiratory illness, reduces mortality, is associated with excess adverse events, and is cost effective. SEARCH METHODS: We searched the Cochrane Airways Trials Register, two clinical trials registries, and reference lists of articles. A number of drug companies we contacted also provided references. The latest search was carried out in December 2017. SELECTION CRITERIA: RCTs that compared live or inactivated virus vaccines with placebo, either alone or with another vaccine, in people with COPD. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. All entries were double-checked. We contacted study authors and drug companies for missing information. We used standard methods expected by Cochrane. MAIN RESULTS: We included 11 RCTs with 6750 participants, but only six of these included people with COPD (2469 participants). The others were conducted on elderly and high-risk individuals, some of whom had chronic lung disease. Interventions compared with placebo were inactivated virus injections and live attenuated intranasal virus vaccines. Some studies compared intra-muscular inactivated vaccine and intranasal live attenuated vaccine with intra-muscular inactivated vaccine and intranasal placebo. Studies were conducted in the UK, USA and Thailand.Inactivated vaccine reduced the total number of exacerbations per vaccinated participant compared with those who received placebo (mean difference (MD) -0.37, 95% confidence interval (CI) -0.64 to -0.11; P = 0.006; two RCTs, 180 participants; low quality evidence). This was due to the reduction in 'late' exacerbations, occurring after three or four weeks (MD -0.39, 95% CI -0.61 to -0.18; P = 0.0004; two RCTs, 180 participants; low quality evidence). Both in people with COPD, and in older people (only a minority of whom had COPD), there were significantly more local adverse reactions in people who had received the vaccine, but the effects were generally mild and transient.There was no evidence of an effect of intranasal live attenuated virus when this was added to inactivated intramuscular vaccination.Two studies evaluating mortality for influenza vaccine versus placebo were too small to have detected any effect on mortality. However, a large study (N=2215) noted that there was no difference in mortality when adding live attenuated virus to inactivated virus vaccination, AUTHORS' CONCLUSIONS: It appeared, from the limited number of RCTs we were able to include, all of which were more than a decade old, that inactivated vaccine reduced exacerbations in people with COPD. The size of effect was similar to that seen in large observational studies, and was due to a reduction in exacerbations occurring three or more weeks after vaccination, and due to influenza. There was a mild increase in transient local adverse effects with vaccination, but no evidence of an increase in early exacerbations. Addition of live attenuated virus to the inactivated vaccine was not shown to confer additional benefit.


Assuntos
Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Pneumopatias Obstrutivas/complicações , Idoso , Progressão da Doença , Humanos , Vacinas contra Influenza/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/uso terapêutico , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/uso terapêutico
19.
J Vet Diagn Invest ; 30(5): 755-759, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29938600

RESUMO

Mycoplasma hyorhinis is an important pathogen of swine that can often occur as a respiratory coinfection with viral pathogens, but can also cause arthritis and polyserositis in infected animals. To date, no assay is available to assess the serologic response to M. hyorhinis vaccines, to our knowledge. We used recombinantly expressed M. hyorhinis p37 protein to monitor the magnitude of the IgG response in vaccinated animals. The assay was able to distinguish animals vaccinated with M. hyorhinis from those vaccinated with the other important Mycoplasma species: M. hyopneumoniae and M. hyosynoviae. When formulated with an ideal adjuvant, inactivated vaccines designed to protect animals against M. hyorhinis induced a measurable and dose-dependent antibody response against the p37 protein. Additionally, the protein appears to be highly conserved between strains of M. hyorhinis isolated in the United States. The specificity of the assay as well as the conservation and immunogenicity of the p37 protein make it an ideal candidate antigen for use in measuring the immune response against M. hyorhinis after vaccination in weaned pigs.


Assuntos
Vacinas Bacterianas/uso terapêutico , Mycoplasma hyorhinis/imunologia , Pneumonia Suína Micoplasmática/prevenção & controle , Vacinas de Produtos Inativados/uso terapêutico , Animais , Anticorpos Anti-Idiotípicos/sangue , Formação de Anticorpos , Vacinas Bacterianas/administração & dosagem , Ensaio de Imunoadsorção Enzimática/veterinária , Mycoplasma hyorhinis/patogenicidade , Sensibilidade e Especificidade , Suínos , Vacinação/veterinária , Vacinas de Produtos Inativados/administração & dosagem
20.
Curr Opin Pharmacol ; 41: 128-136, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29890457

RESUMO

Live attenuated vaccines elicit stronger protective immunity than dead vaccines. Distinct PAMPs designated as vita-PAMPs signify microbial viability to innate immune cells. Two vita-PAMPs have been characterized: cyclic-di-adenosine-monophosphate (c-di-AMP) and prokaryotic messenger RNA (mRNA). c-di-AMP produced by live Gram-positive bacteria elicits augmented production of STING-dependent type-I interferon, whereas prokaryotic mRNA from live bacteria is detected by TLR8 enabling discrimination of live from dead bacteria. Bacterial mRNA from live Gram-negative bacteria triggers a heightened type-I interferon and NLRP3 inflammasome response. By mobilizing unique viability-associated innate responses, vita-PAMPs mobilize adaptive immunity that best elicits protection, including follicular T helper cell and antibody responses. Here, we review the molecular mechanisms that confer the unique adjuvanticity of vita-PAMPs and discuss their applications in vaccine design.


Assuntos
Adjuvantes Imunológicos/farmacologia , Infecções Bacterianas/imunologia , Fosfatos de Dinucleosídeos/farmacologia , Padrões Moleculares Associados a Patógenos/imunologia , RNA Mensageiro/farmacologia , Imunidade Adaptativa , Animais , Humanos , Imunidade Inata , Proteínas de Membrana/imunologia , Viabilidade Microbiana/imunologia , Transdução de Sinais/imunologia , Vacinas Atenuadas/uso terapêutico , Vacinas de Produtos Inativados/uso terapêutico , Vacinas Vivas não Atenuadas/uso terapêutico
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