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1.
Vet Clin North Am Food Anim Pract ; 35(3): 391-403, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31590894

RESUMO

Vaccination is a critical tool in modern animal production and key to maintaining animal health. Adjuvants affect the immune response by increasing the rate, quantity, or quality of the protective response generated by the target antigens. Although adjuvant technology dates back to the nineteenth century, there was relatively little improvement in adjuvant technology before the late twentieth century. With the discovery of molecular pathways that regulate the timing, quantity, and quality of the immune response, new technologies are focused on bringing safer, more effective, and inexpensive adjuvants to commercial use.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Doenças dos Animais/prevenção & controle , Ruminantes/imunologia , Vacinação/veterinária , Adjuvantes Imunológicos/farmacologia , Doenças dos Animais/imunologia , Animais
2.
Medicine (Baltimore) ; 98(33): e16771, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415377

RESUMO

The cell wall skeleton of Bacillus Calmette-Guérin (BCG-CWS) is a bioactive component that is a strong immune adjuvant for cancer immunotherapy. BCG-CWS activates the innate immune system through various pattern recognition receptors and is expected to elicit antigen-specific cellular immune responses when co-administered with tumor antigens. To determine the recommended dose (RD) of BCG-CWS based on its safety profile, we conducted a phase I dose-escalation study of BCG-CWS in combination with WT1 peptide for patients with advanced cancer.The primary endpoint was the proportion of treatment-related adverse events (AEs) at each BCG-CWS dose. The secondary endpoints were immune responses and clinical effects. A BCG-CWS dose of 50, 100, or 200 µg/body was administered intradermally on days 0, 7, 21, and 42, followed by 2 mg of WT1 peptide on the next day. For the escalation of a dose level, 3 + 3 design was used.Study subjects were 18 patients with advanced WT1-expressing cancers refractory to standard anti-cancer therapies (7 melanoma, 5 colorectal, 4 hepatobiliary, 1 ovarian, and 1 lung). Dose-limiting toxicity occurred in the form of local skin reactions in 2 patients at a dose of 200 µg although no serious treatment-related systemic AEs were observed. Neutrophils and monocytes transiently increased in response to BCG-CWS. Some patients demonstrated the induction of the CD4 T cell subset and its differentiation from the naïve to memory phenotype, resulting in a tumor response.The RD of BCG-CWS was determined to be 100 µg/body. This dose was well tolerated and showed promising clinical effects with the induction of an appropriate immune response.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Esqueleto da Parede Celular/uso terapêutico , Mycobacterium bovis , Adjuvantes Imunológicos/administração & dosagem , Adulto , Idoso , Vacina BCG/administração & dosagem , Contagem de Linfócito CD4 , Esqueleto da Parede Celular/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Melanoma/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Resultado do Tratamento
3.
J Microbiol ; 57(9): 821-827, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31452045

RESUMO

Most commercialized virus-like particle (VLP) vaccines use aluminum salt as adjuvant, even though VLPs provoke adequate antibody responses without adjuvant. We do not have detailed knowledge of how adjuvant affects the profile of anti-VLP antibodies. Meanwhile, there is evidence that differences between vaccination protocols influence the glycosylation of antibodies, which may alter their effector functions. In the present study a murine model was used to investigate the effects of dosing schedule and adjuvant on the antibody profiles and glycosylation levels of antigen-specific antibody responses to human papillomavirus type 16 L1 (HPV16 L1) VLPs. Mice received subcutaneously 2,000 ng of antigen divided into 4 or 7 doses. The HPV16 L1 VLPs elicited > 4 log10 anti-HPV16 L1 IgG titers without adjuvant, and aluminum hydroxide as adjuvant increased IgG titers 1.3- to 4-fold and reduced the anti-HPV16 L1 IgG2a / anti-HPV16 L1 IgG1 ratio value (use of aluminum hydroxide reduced the ratio of the IgG2a). Immunization with HPV16 L1 VLPs in combination with Freund's adjuvant enhanced IgG titers 5- to 12-fold. Seven-dose immunization markedly increased anti-HPV16 L1 IgM titers compared to four-dose immunization, as well as increasing the proportion of glycosylated antibodies. Our results suggest that antibody glycosylation can be controlled immunologically, and IgG and IgM profiles and glycosylation profiles of the vaccine-induced antibodies can be used as indicators reflecting the vaccine characteristics. These results indicate that the HPV16 L1 VLP dosing schedule can affect the quality of antigen-specific antibody responses. We suggest that dosing schedules should be noted in vaccination protocols for VLP-based vaccines.


Assuntos
Papillomavirus Humano 16/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antivirais/imunologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Papillomavirus Humano 16/genética , Humanos , Esquemas de Imunização , Camundongos , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia
4.
Vet Immunol Immunopathol ; 213: 109885, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307670

RESUMO

Protec™ is a commercial aquafeed (Skretting Italia) containing a combination of glucans, vitamin C, vitamin E and zinc (immune support pack). No research information concerning its capability to improve fish immune response is available, so in this study the potential immunomodulatory effects of Protec™ were investigated in rainbow trout (Oncorhynchus mykiss). Head kidney (HK) leukocytes from adult fish (100 g, n = 6) were in vitro incubated with Protec™ immune support pack resulting in significantly higher respiratory burst activity and proliferation. Specifically, sonicated Protec™ immune support pack (160 µg/ml) induced a respiratory burst response similar to that promoted by zymosan and lipopolysaccharide (LPS), while non-sonicated Protec™ immune support pack induced a response comparable to that of cells stimulated with phorbol myristate acetate (PMA). Moreover, the proliferation of leukocytes exposed to sonicated Protec™ immune support pack (20 µg/ml) was significantly higher than that of cells stimulated with zymosan, and it was comparable to the proliferation of cells stimulated with phytohaemagglutinin (PHA) and LPS. Afterwards, a feeding trial was performed in a rainbow trout farm. Two groups of juvenile rainbow trout (10 g) were acclimated for 7 weeks before the experiment and fed daily with a commercial control diet (Optiline HE, Skretting Italia) at 2% BW/day. At the end of acclimation, one group of fish was fed with Protec™ diet (Skretting Italia) at 2% BW/day whereas the other group continued to feed the control diet at the same level for further 4 weeks. Then, fish were sampled (HK leukocytes from n = 6 fish/group, serum from n = 12 fish/group) or intraperitoneally vaccinated against lactococcosis (n = 160/dietary group/time point). Fish fed the same diets for further 4 weeks after vaccination, then feeding returned to the control diet in both groups until the end of the trial. The specific antibody response was recorded at 4 and 8 weeks after vaccination (n = 12 fish/group). The administration of Protec™ significantly enhanced the respiratory burst activity of leukocytes and the synthesis of specific IgM against Lactococcus garvieae, whereas the serum lysozyme activity was unaffected. The present research suggests that the administration of Protec™ can improve both innate and adaptive immune response of rainbow trout, proving to be an interesting strategy for enhancing the immune reactivity of fish to vaccines.


Assuntos
Ração Animal , Anticorpos Antibacterianos/sangue , Infecções por Bactérias Gram-Positivas/veterinária , Imunidade Inata , Lactococcus , Oncorhynchus mykiss/imunologia , Imunidade Adaptativa , Adjuvantes Imunológicos/administração & dosagem , Animais , Proliferação de Células , Dieta/veterinária , Feminino , Doenças dos Peixes/imunologia , Infecções por Bactérias Gram-Positivas/imunologia , Imunoglobulina M/sangue , Leucócitos/imunologia , Oncorhynchus mykiss/microbiologia , Explosão Respiratória
5.
Vet Immunol Immunopathol ; 212: 1-8, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31213246

RESUMO

Bovine mastitis caused by Staphylococcus aureus is a serious problem in dairy production and effective immunoprophylaxis is an unmet goal so far. The objective of this work was to assess the humoral immune response of heifer calves against two recombinant S. aureus antigens: Clumping factor A (ClfA) and Fibronectin Binding Protein A (FnBPA), formulated with a novel adjuvant based on cationic liposomes (Lip) and CpG oligodeoxynucleotides (CpG-ODN). Six groups of 6-8 months old heifer calves received three doses biweekly of antigens, formulated with Al(OH)3, liposomes, CpG-ODN or Lip + CpG-ODN. Animals also received a fourth dose after a year (day 410) and a booster before calving. The administration of Al(OH)3+FnBPA/ClfA and Lip + FnBPA/ClfA + CpG-ODN induced the highest specific IgG levels, after the first 3 doses and induced a fast increase of antibodies after the fourth dose. All the formulations stimulated the production of specific IgG1, after the third and fourth dose. Specific IgG2 for both proteins was only stimulated after the fourth dose by Lip + FnBPA/ClfA + CpG-ODN. Pre-calving immunisation with Lip + FnBPA/ClfA + CpG-ODN led to the highest IgG levels during the calving period and to the production of the IgG2 subclass. The formulation was also able to stimulate the highest antibody levels in milk, 30 and 45 days after pre-calving booster. The combination of liposomes and CpG-ODN as adjuvant for a subunit vaccine, together with the immunisation schedule described, induced a strong humoral immune response with production of specific IgG2. The formulation demonstrated to induce immune memory allowing the application of a single pre-calving booster to maintain high antibody levels throughout the period of increased susceptibility to intramammary infections.


Assuntos
Antígenos de Bactérias/imunologia , Imunidade Humoral , Mastite Bovina/prevenção & controle , Oligodesoxirribonucleotídeos/farmacologia , Adjuvantes Imunológicos/administração & dosagem , Fatores Etários , Animais , Anticorpos Antibacterianos/sangue , Bovinos , Imunoglobulina G/sangue , Memória Imunológica , Lipossomos/farmacologia , Mastite Bovina/imunologia , Mastite Bovina/microbiologia , Staphylococcus aureus , Vacinação , Soro do Leite/imunologia
6.
Vet Immunol Immunopathol ; 212: 27-37, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31213249

RESUMO

Toll-like receptor (TLR) agonists can effectively stimulate antigen-presenting cells (APCs) and are anticipated to be promising adjuvants in combination with inactivated vaccines. In this study, the adjuvant potential of three different TLR-agonists were compared with an oil-in-water (O/W) adjuvant in combination with inactivated porcine reproductive and respiratory syndrome virus (iPRRSV) applied by different administration routes: intramuscular (i.m.) or into the skin using dissolving microneedle (DMN) patches. Pigs received a prime vaccination followed by a booster vaccination four weeks later. TLR1/2 (Pam3Cys), TLR7/8 (R848) or TLR9 (CpG ODN) agonists were used as adjuvant in combination with iPRRSV strain 07V063. O/W adjuvant (Montanide™) was used as reference control adjuvant and one group received a placebo vaccination containing diluent only. All animals received a homologous challenge with PRRSV three weeks after the booster vaccination. Antibody and IFN-γ production, serum cytokines and viremia were measured at several time-points after vaccination and/or challenge, and lung pathology at necropsy. Our results indicate that a TLR 1/2, 7/8 or 9 agonist as adjuvant with iPRRSV does not induce a detectable PRRSV-specific immune response, independent of the administration route. However, the i.m. TLR9 agonist group showed reduction of viremia upon challenge compared to the non-vaccinated animals, supported by a non-antigen-specific IFN-γ level after booster vaccination and an anamnestic antibody response after challenge. Montanide™-adjuvanted iPRRSV induced antigen-specific immunity after booster combined with reduction of vireamia. Skin application of TLR7/8 agonist, but not the other agonists, induced a local skin reaction. Further research is needed to explore the potential of TLR agonists as adjuvants for inactivated porcine vaccines with a preference for TLR9 agonists.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Oligodesoxirribonucleotídeos/imunologia , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Receptor Toll-Like 9/agonistas , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/sangue , Citocinas/sangue , Citocinas/imunologia , Masculino , Oligodesoxirribonucleotídeos/administração & dosagem , Síndrome Respiratória e Reprodutiva Suína/imunologia , Vírus da Síndrome Respiratória e Reprodutiva Suína , Suínos , Receptor Toll-Like 9/imunologia , Vacinação , Vacinas de Produtos Inativados/imunologia , Viremia
7.
Int J Infect Dis ; 85: 70-73, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31132473

RESUMO

Varicella zoster virus (VZV) pneumonia is associated with significant mortality, especially in the immunocompromised host. VZV-specific immunoglobulins (VZIG) are currently used as post-exposure prophylaxis for at-risk patients, but not as adjunctive therapy. A novel case of VZV pneumonia in an immunocompromised patient, treated successfully with intravenous VZIG in combination with acyclovir, is reported here.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Anticorpos Antivirais/uso terapêutico , Herpesvirus Humano 3/imunologia , Pneumonia Viral/tratamento farmacológico , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológico , Aciclovir/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Administração Intravenosa , Adulto , Anticorpos Antivirais/administração & dosagem , Antivirais/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Masculino
8.
Fish Shellfish Immunol ; 91: 251-263, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31121290

RESUMO

Soiny mullet (Liza haematocheila) is an important economic fish species in China, but stress and diseases have seriously restricted its culture. There are no effective methods including vaccines to prevent or control these diseases. Alternative methods should be employed, such as using novel immunostimulant poly-ß-hydroxybutyrate (PHB). The present study aimed to evaluate effects of dietary PHB supplementation on the growth, antioxidant enzymes activity, immune-related genes expression and intestinal microbiota in soiny mullet. The fish was fed for 30 or 60 days with six diets at different PHB supplementation of 0, 0.5, 1, 2, 4 and 8%, named as groups P0, P0.5, P1, P2, P4 and P8. The results showed that the weight gain and specific growth rate of fish in P2 and P0.5 groups were significantly higher than those in control P0 group at 30 and 60 days, respectively (P < 0.05). The antioxidant enzymes activity of catalase and superoxide dismutase in serum were significantly increased in P0.5/P1/P2 groups after 30 days. The transcriptional levels of penicillin-binding protein A and interleukin-8 analyzed by qRT-PCR were significantly upregulated in P2 and P4 groups compared to those in P0/P0.5/P1/P8 groups at 30 days. The transcriptional level of major histocompatibility complex class II in P2 group was significantly upregulated, and aldehyde oxidase downregulated compared to P0 group. Intestinal microbiota analysis by Illumina high-throughput sequencing showed that the microbiota diversity was not changed significantly, but the microbiota structure shifted significantly post PHB treatment. At the phyla level, Firmicutes and Proteobacteria were predominant in both P0 and P2 groups. At the genus level, the relative abundance of Bacillus spp. in P2 group increased significantly, and abundance of Achromobacter spp. decreased significantly. KEGG pathway analysis by PICRUSt showed that oral administration PHB significantly upregulated abundances of genes responsible for 10 pathways and downregulated genes involved in 17 pathways. In conclusion, soiny mullet fed with 2% PHB supplemental diets for 30 days showed better growth performance, higher antioxidant enzymes activity and immune-related genes expression. Their regulation of growth and immunity might be related with the intestinal microbiota change post PHB supplementation. It will provide very useful basic information to study the regulation mechanism of PHB in aquatic animals, and provide good green method to prevent disease in soiny mullet.


Assuntos
Adjuvantes Imunológicos/metabolismo , Microbioma Gastrointestinal , Hidroxibutiratos/metabolismo , Poliésteres/metabolismo , Smegmamorpha/imunologia , Adjuvantes Imunológicos/administração & dosagem , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Microbioma Gastrointestinal/efeitos dos fármacos , Hidroxibutiratos/administração & dosagem , Intestinos/microbiologia , Poliésteres/administração & dosagem , Smegmamorpha/crescimento & desenvolvimento , Smegmamorpha/microbiologia
9.
Health Qual Life Outcomes ; 17(1): 80, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060567

RESUMO

BACKGROUND: This study aims to describe the short-term reactogenicity of the AS03-adjuvanted H5N1 vaccine expressed through adverse events (AEs) and quality-adjusted life-day (QALD) scores. The AEs are likely to be short-term and therefore the quality of life (QoL) questionnaire, SF-36v2, was administered daily to record changes over seven days. A more sensitive application of this instrument should allow for a better understanding of short-term tolerability of adjuvanted vaccines. METHODS: Participants (N = 50) received a 2-dose vaccination schedule. Solicited (collected daily: days 0 to 7 [post dose 1] and 21 to 28 [post dose 2]) and unsolicited (collected weekly until day 21) AEs were collected via diary cards. The QoL questionnaires were completed daily (days 0-6) and weekly (days 0, 6, 21, 27) after dose one. Questionnaire data were transformed into SF-6D scores to report QALDs. It was hypothesized post-hoc that the QALD and daily AEs scores should correlate if discrete QoL-changes were captured. RESULTS: Pain (92%) and muscle ache (66%) were the most commonly reported solicited local and general AEs respectively, neither increased in intensity nor in frequency after dose 2. No safety concerns were identified during the study. A correlation between the daily AEs and QALD scores existed (correlation coefficient, - 0.97 (p < 0.001)). The impact of the AEs scores on the QALD was marginal (- 0.02 max for one day). CONCLUSION: Similarly with other H5N1 studies, no safety concern was identified throughout the study. Some time-limited variations in QALD-scores were reported. Our results imply that daily administration of the SF-36v2 captures changes in QALD-scores. TRIAL REGISTRATION: ClinicalTrials.gov . NCT01788228. Registered 11 February 2013.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Vacinas contra Influenza/efeitos adversos , Influenza Humana/prevenção & controle , Qualidade de Vida/psicologia , Adjuvantes Imunológicos/administração & dosagem , Adulto , Feminino , Humanos , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/administração & dosagem , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Fatores de Tempo , Vacinação/efeitos adversos , Vacinação/psicologia
10.
Nat Commun ; 10(1): 2025, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31048681

RESUMO

Combined checkpoint blockade (e.g., PD1/PD-L1) with traditional clinical therapies can be hampered by side effects and low tumour-therapeutic outcome, hindering broad clinical translation. Here we report a combined tumour-therapeutic modality based on integrating nanosonosensitizers-augmented noninvasive sonodynamic therapy (SDT) with checkpoint-blockade immunotherapy. All components of the nanosonosensitizers (HMME/R837@Lip) are clinically approved, wherein liposomes act as carriers to co-encapsulate sonosensitizers (hematoporphyrin monomethyl ether (HMME)) and immune adjuvant (imiquimod (R837)). Using multiple tumour models, we demonstrate that combining nanosonosensitizers-augmented SDT with anti-PD-L1 induces an anti-tumour response, which not only arrests primary tumour progression, but also prevents lung metastasis. Furthermore, the combined treatment strategy offers a long-term immunological memory function, which can protect against tumour rechallenge after elimination of the initial tumours. Therefore, this work represents a proof-of-concept combinatorial tumour therapeutics based on noninvasive tumours-therapeutic modality with immunotherapy.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Imunoterapia/métodos , Metástase Neoplásica/terapia , Neoplasias/terapia , Terapia por Ultrassom/métodos , Animais , Antineoplásicos Imunológicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Linhagem Celular Tumoral/transplante , Terapia Combinada/métodos , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Hematoporfirinas/administração & dosagem , Humanos , Imiquimode/administração & dosagem , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Metástase Neoplásica/imunologia , Neoplasias/imunologia , Neoplasias/patologia , Resultado do Tratamento
11.
mSphere ; 4(3)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043512

RESUMO

Campylobacter jejuni is among the most common causes of diarrheal disease worldwide and efforts to develop protective measures against the pathogen are ongoing. One of the few defined virulence factors targeted for vaccine development is the capsule polysaccharide (CPS). We have developed a capsule conjugate vaccine against C. jejuni strain 81-176 (CPS-CRM) that is immunogenic in mice and nonhuman primates (NHPs) but only moderately immunogenic in humans when delivered alone or with aluminum hydroxide. To enhance immunogenicity, two novel liposome-based adjuvant systems, the Army Liposome Formulation (ALF), containing synthetic monophosphoryl lipid A, and ALF plus QS-21 (ALFQ), were evaluated with CPS-CRM in this study. In mice, ALF and ALFQ induced similar amounts of CPS-specific IgG that was significantly higher than levels induced by CPS-CRM alone. Qualitative differences in antibody responses were observed where CPS-CRM alone induced Th2-biased IgG1, whereas ALF and ALFQ enhanced Th1-mediated anti-CPS IgG2b and IgG2c and generated functional bactericidal antibody titers. CPS-CRM + ALFQ was superior to vaccine alone or CPS-CRM + ALF in augmenting antigen-specific Th1, Th2, and Th17 cytokine responses and a significantly higher proportion of CD4+ IFN-γ+ IL-2+ TNF-α+ and CD4+ IL-4+ IL-10+ T cells. ALFQ also significantly enhanced anti-CPS responses in NHPs when delivered with CPS-CRM compared to alum- or ALF-adjuvanted groups and showed the highest protective efficacy against diarrhea following orogastric challenge with C. jejuni This study provides evidence that the ALF adjuvants may provide enhanced immunogenicity of this and other novel C. jejuni capsule conjugate vaccines in humans.IMPORTANCE Campylobacter jejuni is a leading cause of diarrheal disease worldwide, and currently no preventative interventions are available. C. jejuni is an invasive mucosal pathogen that has a variety of polysaccharide structures on its surface, including a capsule. In phase 1 studies, a C. jejuni capsule conjugate vaccine was safe but poorly immunogenic when delivered alone or with aluminum hydroxide. Here, we report enhanced immunogenicity of the conjugate vaccine delivered with liposome adjuvants containing monophosphoryl lipid A without or with QS-21, known as ALF and ALFQ, respectively, in preclinical studies. Both liposome adjuvants significantly enhanced immunity in mice and nonhuman primates and improved protective efficacy of the vaccine compared to alum in a nonhuman primate C. jejuni diarrhea model, providing promising evidence that these potent adjuvant formulations may enhance immunogenicity in upcoming human studies with this C. jejuni conjugate and other malaria and HIV vaccine platforms.


Assuntos
Vacinas Bacterianas/imunologia , Infecções por Campylobacter/prevenção & controle , Imunogenicidade da Vacina , Lipídeo A/análogos & derivados , Saponinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antibacterianos/sangue , Infecções por Campylobacter/imunologia , Campylobacter jejuni/imunologia , Citocinas/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Lipídeo A/administração & dosagem , Lipossomos/administração & dosagem , Lipossomos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Primatas , Células Th1/imunologia , Células Th2/imunologia , Vacinas Conjugadas/administração & dosagem
12.
An Bras Dermatol ; 94(2): 221-223, 2019 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31090830

RESUMO

Vegetative chronic genital herpes is an atypical presentation of herpes simplex 2 that it is usually seen in patients coinfected with human immunodeficiency virus. Clinically, it is characterized by extensive ulcers that evolve to chronification and hypertrophic pseudotumor forms. Antiviral drugs are recommended for the treatment, and acyclovir is the most used one. Foscarnet is the treatment of choice to resistant cases, although treatment failure has been reported. We report a male patient, previously diagnosed with human immunodeficiency virus who developed vegetative chronic genital herpes resistant to acyclovir and successfully treated with imiquimod.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Adjuvantes Imunológicos/uso terapêutico , Herpes Genital/tratamento farmacológico , Imiquimode/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Adulto , Doença Crônica , Relação Dose-Resposta a Droga , Herpes Genital/diagnóstico , Humanos , Imiquimode/administração & dosagem , Masculino , Resultado do Tratamento
13.
Cancer Immunol Immunother ; 68(7): 1211-1222, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31069460

RESUMO

Human tumor cells express antigens that serve as targets for the host cellular immune system. This phase 1 dose-escalating study was conducted to assess safety and tolerability of G305, a recombinant NY-ESO-1 protein vaccine mixed with glucopyranosyl lipid A (GLA), a synthetic TLR4 agonist adjuvant, in a stable emulsion (SE). Twelve patients with solid tumors expressing NY-ESO-1 were treated using a 3 + 3 design. The NY-ESO-1 dose was fixed at 250 µg, while GLA-SE was increased from 2 to 10 µg. Safety, immunogenicity, and clinical responses were assessed prior to, during, and at the end of therapy. G305 was safe and immunogenic at all doses. All related AEs were Grade 1 or 2, with injection site soreness as the most commonly reported event (100%). Overall, 75% of patients developed antibody response to NY-ESO-1, including six patients with increased antibody titer ( ≥ 4-fold rise) and three patients with seroconversion from negative (titer < 100) to positive (titer ≥ 100). CD4 T-cell responses were observed in 44.4% of patients; 33.3% were new responses and 1 was boosted ( ≥ 2-fold rise). Following treatment, 8 of 12 patients had stable disease for 3 months or more; at the end of 1 year, three patients had stable disease and nine patients were alive. G305 is a potent immunotherapeutic agent that can stimulate NY-ESO-1-specific antibody and T-cell responses. The vaccine was safe at all doses of GLA-SE (2-10 µg) and showed potential clinical benefit in this population of patients.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Antígenos de Neoplasias/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Glucosídeos/administração & dosagem , Lipídeo A/administração & dosagem , Proteínas de Membrana/administração & dosagem , Neoplasias/terapia , Adjuvantes Imunológicos/efeitos adversos , Adulto , Idoso , Antígenos de Neoplasias/efeitos adversos , Antígenos de Neoplasias/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/imunologia , Drogas em Investigação/administração & dosagem , Drogas em Investigação/efeitos adversos , Feminino , Glucosídeos/efeitos adversos , Glucosídeos/imunologia , Humanos , Imunogenicidade da Vacina , Injeções Intramusculares , Lipídeo A/efeitos adversos , Lipídeo A/imunologia , Masculino , Proteínas de Membrana/efeitos adversos , Proteínas de Membrana/imunologia , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/patologia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/imunologia , Receptor 4 Toll-Like/agonistas , Receptor 4 Toll-Like/imunologia , Resultado do Tratamento , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vacinas Sintéticas/imunologia , Adulto Jovem
14.
Microbiol Immunol ; 63(7): 269-279, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31141221

RESUMO

Pseudorabies, a herpesvirus infection, is mainly controlled by using attenuated live vaccines. In this study, the effect of ginseng stem and leaf saponins (GSLS) in combination with selenium (Se; in the form of sodium selenite) on vaccination against attenuated pseudorabies virus (aPrV) was evaluated. It was found that GSLS and Se have an adjuvant effect and that a combination of GSLS and Se stimulates significantly enhanced immune responses than does GSLS or Se alone. Following oral administration of GSLS, mice immunized with an attenuated PrV vaccine diluted in Se-containing physiological saline solution (PSS) provoked a significantly stronger gB-specific serum antibodies response (IgG, IgG1 and IgG2a), enhanced lymphocyte proliferation and cytolytic activity of NK cells, along with higher production of cytokines (IFN-γ, IL-12, IL-5 and IL-10) by splenocytes. Notably, the combination of GSLS and Se conferred a much higher resistance to fPrV challenge after immunization of the mice with aPrV vaccine. This study offers convincing experimental evidence that an injection of Se with oral GSLS is a promising adjuvant combination that improves the efficacy of vaccination against PrV and deserves further study regarding improvement of responses to other animal vaccines.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Herpesvirus Suídeo 1/imunologia , Panax/química , Folhas de Planta/química , Vacinas contra Pseudorraiva/imunologia , Saponinas/farmacologia , Selênio/farmacologia , Vacinas Atenuadas/imunologia , Adjuvantes Imunológicos/administração & dosagem , Administração Oral , Animais , Formação de Anticorpos , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Combinação de Medicamentos , Feminino , Febre Aftosa/prevenção & controle , Imunização , Imunoglobulina G/sangue , Células Matadoras Naturais/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Doença de Newcastle/prevenção & controle , Extratos Vegetais/farmacocinética , Pseudorraiva/prevenção & controle , Saponinas/administração & dosagem , Selênio/administração & dosagem , Vacinação , Vacinas Atenuadas/administração & dosagem
15.
Fish Shellfish Immunol ; 90: 264-273, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31054356

RESUMO

We investigated the effects of icariin (ICA) on growth performance, antioxidant capacity and non-specific immunity in Chinese mitten crab (Eriocheir sinensis). A total of 200 healthy crabs (average weight: 33.58 ±â€¯0.05 g) were randomly assigned to four treatments with five replicates, each with ten individuals per pool. There were four dietary treatments: the control group (fed with the basal diet), the ICA 50 group, the ICA100 group, and the ICA 200 group (fed with the basal diet supplemented with 50, 100, and 200 mg/kg ICA, respectively). These diets were provided for 8 weeks. Results indicated that ICA100 crabs had higher weight gain (WG), specific growth rate (SGR) and survival rate (SR) than the controls. Protein carbonyl content (PCC) and malondialdehyde (MDA) concentrations in the haemolymph and hepatopancreas of ICA100 crabs were significantly lower than in the control group, while the superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were significantly higher. The activities of PO, LZM, ACP and AKP were significantly enhanced with ICA supplementation at 50 and 100 mg/kg, yet decreased subsequently at 200 mg/kg. Furthermore, supplementation of 100 mg/kg ICA up-regulated the mRNA expression of prophenoloxidase (proPO), catalase (CAT), mitochondrial manganese superoxide dismutase (mtMnSOD), thioredoxin-1 (Trx1) and peroxiredoxin 6 (Prx6), while the mRNA expression of toll like receptors (TLRs), NF-κB-like transcription factor Relish and lipopolysaccharide-induced TNF-α factor (LITAF) were down-regulated in the hepatopancreas (P < 0.05). These findings indicate that dietary ICA supplementation at an optimum dose of 100 mg/kg may be effective in improving growth performance, antioxidant capability and non-specific immunity of Chinese mitten crab.


Assuntos
Adjuvantes Imunológicos/metabolismo , Braquiúros/imunologia , Flavonoides/metabolismo , Imunidade Inata/efeitos dos fármacos , Adjuvantes Imunológicos/administração & dosagem , Ração Animal/análise , Animais , Antioxidantes , Braquiúros/genética , Braquiúros/crescimento & desenvolvimento , Braquiúros/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Flavonoides/administração & dosagem , Distribuição Aleatória
16.
Int J Nanomedicine ; 14: 3221-3234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31123399

RESUMO

Background: Poly (lactic-co-glycolic acid) (PLGA) nanoparticles and surface modified PLGA nanoparticles have been widely studied as antigens or drugs carriers due to their controlled release characteristics and biocompatibility. However, most PLGA nanoparticles have lower antigens loading efficiency and adjuvanticity. Purpose: The aim of this study was to improve the antigen loading efficiency and adjuvant activity of PLGA nanoparticles. Materials and methods: Surface cationic polymer modification can improve the antigens loading efficiency of PLGA nanoparticles by surface adsorption. Therefore, in this study, chitosan modified PLGA nanoparticles (CS-AHPP/OVA), polyethyleneimine modified PLGA nanoparticles (PEI-AHPP/OVA), and ε-Poly-L-lysine modified PLGA nanoparticles (εPL-AHPP/OVA) were prepared as antigen delivery carriers to investigate the characterization and stability of these nanoparticles. These nanoparticles were evaluated for their efficacies as adjuvants pre- and post-modification. Results: The AHP and OVA-loaded PLGA nanoparticles (AHPP/OVA) were positively charged after surface cationic polymers modification, and their structural integrity was maintained. Their antigen loading capacity and stability of nanoparticles were improved by the surface cationic polymers modification. Increased positive surface charge resulted in greater OVA adsorption capacity. Among AHPP/OVA and the three surface cationic polymers synthesized from modified PLGA nanoparticles, PEI-AHPP/OVA showed the highest antigen loading efficiency and good stability. AHPP/OVA, CS-AHPP/OVA PEI-AHPP/OVA, and εPL-AHPP/OVA formulations significantly enhanced lymphocyte proliferation and improved the ratio of CD4+/CD8+ T cells. In addition, AHPP/OVA, PEI-AHPP/OVA and εPL-AHPP/OVA formulations induced secretion of cytokines (TNF-α, IFN-γ, IL-4, and IL-6), antibodies (IgG) and antibody subtypes (IgG1 and IgG2a) in immunized mice. These results demonstrate that these formulations generated a strong Th1-biased immune response. Among them, PEI-AHPP/OVA induced the strongest Th1-biased immune response. Conclusion: In conclusion, PEI-AHPP/OVA nanoparticles may be a potential antigen delivery system for the induction of strong immune responses.


Assuntos
Sistemas de Liberação de Medicamentos , Mel , Imunidade Celular , Ovalbumina/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polissacarídeos/química , Vacinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Formação de Anticorpos , Antígenos/metabolismo , Cátions , Proliferação de Células , Quitosana/química , Citocinas/sangue , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Ativação Linfocitária , Camundongos Endogâmicos ICR , Nanopartículas/química , Ovalbumina/imunologia , Polietilenoimina/química , Baço/citologia , Linfócitos T/imunologia , Vacinação , Vacinas/imunologia
17.
Crit Rev Oncol Hematol ; 137: 1-8, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31014505

RESUMO

Bone-modifying agents like bisphosphonates and receptor activator of nuclear factor kappaß ligand (RANK-L) inhibitors are used as supportive treatments in breast cancer patients with bone metastases to prevent skeletal-related events (SREs). Due to missing head-to-head comparisons, a network meta-analysis was performed to provide a hierarchy of these therapeutic options. Through a systematic literature search, 21 randomized controlled trials (RCTs) that fulfilled the inclusion criteria were identified. To prevent SREs, the ranking through P-scores showed denosumab (RR: 0.62; 95%CI: 0.50-0.76), zoledronic acid (RR: 0.72; 95%CI: 0.61-0.84) and pamidronate (RR: 0.76; 95%CI: 0.67-0.85) to be significantly superior to placebo. Due to insufficient or heterogeneous data, overall survival, quality of life, pain response and adverse events were not able to be analyzed within the network. Although data were sparse on adverse events, the risk of significant adverse events appeared low. The results of this review can therefore be used to formulate clinical studies more precisely in order to standardise and focus on patient-relevant outcomes.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/tratamento farmacológico , Difosfonatos/administração & dosagem , Receptor Ativador de Fator Nuclear kappa-B/antagonistas & inibidores , Adjuvantes Imunológicos/administração & dosagem , Neoplasias da Mama/patologia , Feminino , Humanos , Meta-Análise em Rede , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
PLoS Negl Trop Dis ; 13(4): e0007316, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31026260

RESUMO

INTRODUCTION: Chikungunya virus (CHIKV) is a re-emerging pathogen responsible for causing outbreaks of febrile disease accompanied with debilitating joint pain. Symptoms typically persist for two weeks, but more severe and chronic chikungunya illnesses have been reported, especially in the elderly. Currently, there are no licensed vaccines or antivirals against CHIKV available. In this study, we combined a CHIK virus-like particle (VLP) vaccine with different adjuvants to enhance immunogenicity and protection in both, adult and aged mice. METHODS: CHIK VLP-based vaccines were tested in 6-8-week-old (adult) and 18-24-month-old (aged) female C57BL/6J mice. Formulations contained CHIK VLP alone or adjuvants: QuilA, R848, or Imject Alum. Mice were vaccinated three times via intramuscular injections. CHIKV-specific antibody responses were characterized by IgG subclass using ELISA, and by microneutralization assays. In addition, CHIKV infections were characterized in vaccinated and non-vaccinated adult mice and compared to aged mice. RESULTS: In adult mice, CHIKV infection of the right hind foot induced significant swelling, which peaked by day 7 post-infection at approximately 170% of initial size. Viral titers peaked at 2.53 × 1010 CCID50/ml on day 2 post-infection. Mice vaccinated with CHIK VLP-based vaccines developed robust anti-CHIKV-specific IgG antibody responses that were capable of neutralizing CHIKV in vitro. CHIK VLP alone or CHIK plus QuilA administered by IM injections protected 100% of mice against CHIKV. In contrast, the antibody responses elicited by the VLP-based vaccines were attenuated in aged mice, with negligible neutralizing antibody titers detected. Unvaccinated, aged mice were resistant to CHIKV infection, while vaccination with CHIKV VLPs exacerbated disease. CONCLUSIONS: Unadjuvanted CHIK VLP vaccination elicits immune responses that protect 100% of adult mice against CHIKV infection. However, an improved vaccine/adjuvant combination is still necessary to enhance the protective immunity against CHIKV in the aged.


Assuntos
Febre de Chikungunya/induzido quimicamente , Febre de Chikungunya/prevenção & controle , Vírus Chikungunya/crescimento & desenvolvimento , Vacinas de Partículas Semelhantes a Vírus/efeitos adversos , Vacinas Virais/efeitos adversos , Adjuvantes Imunológicos/administração & dosagem , Fatores Etários , Compostos de Alúmen/administração & dosagem , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Febre de Chikungunya/imunologia , Vírus Chikungunya/imunologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Imunoglobulina G/sangue , Injeções Intramusculares , Camundongos Endogâmicos C57BL , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Vacinas Virais/administração & dosagem
19.
Virol Sin ; 34(3): 324-333, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30989429

RESUMO

Interferon, a natural protein that is produced by a variety of cells during viral infection, activates the transcription of multiple functional genes in cells, regulates synergy among various signaling pathways, and mediates many biological functions such as antiviral activity, immune regulation, and cell growth. However, clinical research on interferon in livestock is lacking. In this study, recombinant porcine interferon (PoIFNα) was used as an adjuvant, in combination with inactivated influenza virus, to vaccinate 6-week-old pigs via nasal infusion. The transcription of target genes was then monitored and the functions of PoIFNα were determined with respect to the activation of mucosal immunity. We found that a combination of low-dose PoIFNα and inactivated influenza virus could significantly up-regulate the expression of immunoregulatory cytokines such as IL-2, IL-18, IFN-γ, IL-6, and IL-10 by real-time PCR, suggesting the induction of a strong mucosal innate immune response after administration. In addition, low-dose PoIFNα can significant enhancing the transcription of genes encoding homing factors including CCR9 and CCR10 (P < 0.001), thereby resulting in the induction of higher levels of HA-specific antibodies (P < 0.05), which can be determined by ELISA and IFA. Post-immunization challenges with H1N1 virus demonstrated that PoIFNα, combined with inactivated influenza virus, could alleviate clinical signs in pigs during the early stages of viral infection. These studies reveal low-dose PoIFNα as a potential mucosal adjuvant for influenza virus in pigs.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Imunidade nas Mucosas , Vacinas contra Influenza/imunologia , Interferon-alfa/imunologia , Infecções por Orthomyxoviridae/veterinária , Administração Intranasal , Animais , Anticorpos Antivirais/imunologia , Citocinas/genética , Citocinas/imunologia , Imunidade Inata , Vacinas contra Influenza/administração & dosagem , Interferon-alfa/administração & dosagem , Infecções por Orthomyxoviridae/prevenção & controle , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Suínos , Vacinação
20.
Sci Total Environ ; 668: 1055-1063, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31018447

RESUMO

New adjuvant formulations, based on proteoliposomes <40 nm and cochleates <100 nm, without Al(OH)3 adjuvant, were evaluated regarding their ability to generate Th1 immune response through a Delayed -Type Hypersensitivity Test, at the mouse model, by using a Neisseria meningitidis B protein complex as antigen. The formulations were administered by intramuscular (IM) (2 inoculations - at baseline and after 14 days) and intranasal (IN) (3 inoculations at 7 days) immunization pathways. All IM immunized groups were able to induce similar response to these formulations as well as to VA-MENGOC-BC® vaccine - containing Al(OH)3 adjuvant (used as positive control of the trial). In all groups, the induced inflammation (IP) rate was statistically higher than in the negative control group (CN) (p < 0.05). Immunogenicity, measured by HSR and CD4+ lymphocyte increase was equivalent to the control vaccine and most important, granuloma reactogenicity at the site of injection was eliminated, fact demonstrated by histological study. All groups of animals immunized by IN route showed HSR reactions and statistically significant differences with respect to the CN group. However, IP values were lower, with statistical differences (p < 0.05) for the same adjuvant formulation IM administered, except the AIF2-nCh formulation that generated statistically similar induction (p > 0.05) by both immunization pathways, suggesting it to be the best candidate for the next IN trial. Proteoliposome and cochleate formulations tested were able to mount potent Th-1 immune response, equivalent to the original vaccine formulation, with the advantage of less reactogenicity in the site of the injection, caused by the toxicity of Al(OH)3 adjuvant gel.


Assuntos
Adjuvantes Imunológicos/uso terapêutico , Antígenos de Bactérias/imunologia , Imunidade Celular , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Animais , Injeções Intramusculares , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neisseria meningitidis , Proteolipídeos
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