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1.
Parasitol Int ; 86: 102446, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34481947

RESUMO

After many years of the excessive use of praziquantel against Schistosoma mansoni (S. mansoni), it has already led to the development of drug resistance. While schistosomiasis is still affecting millions of people every year, vaccination may be one realistic alternative way to control the disease. Currently, S. mansoni 14-kDa fatty acid-binding protein (Sm14) has shown promising results as a vaccine antigen. Yet, the use of an adjuvant may be necessary to further increase the effectiveness of the vaccine. Herein, we investigated the potential of using heat-killed Cutibacterium acnes (C. acnes) as an adjuvant for recombinant Sm14 (rSm14). Immunization of mice with C. acnes-adjuvanted rSm14 showed increased humoral immune responses, compared with mice immunized with rSm14 alone. Additionally, C. acnes-adjuvanted rSm14 vaccination provided higher protection to mice against S. mansoni infection and liver injuries. These results suggest that C. acnes increases the immunogenicity of rSm14, which leads to better protection against S. mansoni infection. Therefore, heat-killed C. acnes may be a promising adjuvant to use with rSm14.


Assuntos
Proteínas de Transporte de Ácido Graxo/imunologia , Proteínas de Helminto/imunologia , Imunogenicidade da Vacina , Propionibacteriaceae/química , Schistosoma mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Vacinas/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos BALB C
2.
Int J Mol Sci ; 22(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34639235

RESUMO

Nanomaterials have found extensive interest in the development of novel vaccines, as adjuvants and/or carriers in vaccination platforms. Conjugation of protein antigens at the particle surface by non-covalent adsorption is the most widely used approach in licensed particulate vaccines. Hence, it is essential to understand proteins' structural integrity at the material interface in order to develop safe-by-design nanovaccines. In this study, we utilized two model proteins, the wild-type allergen Bet v 1 and its hypoallergenic fold variant (BM4), to compare SiO2 nanoparticles with Alhydrogel® as particulate systems. A set of biophysical and functional assays including circular dichroism spectroscopy and proteolytic degradation was used to examine the antigens' structural integrity at the material interface. Conjugation of both biomolecules to the particulate systems decreased their proteolytic stability. However, we observed qualitative and quantitative differences in antigen processing concomitant with differences in their fold stability. These changes further led to an alteration in IgE epitope recognition. Here, we propose a toolbox of biophysical and functional in vitro assays for the suitability assessment of nanomaterials in the early stages of vaccine development. These tools will aid in safe-by-design innovations and allow fine-tuning the properties of nanoparticle candidates to shape a specific immune response.


Assuntos
Alérgenos/imunologia , Antígenos de Plantas/imunologia , Epitopos/imunologia , Ativação Linfocitária/imunologia , Nanopartículas/química , Dióxido de Silício/química , Vacinas/imunologia , Alérgenos/química , Humanos , Hidrogéis , Imunoglobulina E/imunologia , Hipersensibilidade Respiratória/imunologia , Linfócitos T/imunologia
3.
PLoS One ; 16(10): e0258252, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34679104

RESUMO

BACKGROUND: Vaccine hesitancy is a complex, contested social phenomenon and existing research highlights the multifaceted role of trust in strengthening vaccine confidence. However, understanding public engagement with vaccination through the lens of (mis)trust requires more contextual evidence on trust's qualitative determinants. This includes expanding the geographic focus beyond current studies' focus on High Income Countries. Furthermore, obstacles remain in effectively integrating social science findings in the design of vaccine deployment strategies, and in ensuring that those who implement interventions and are affected by them are directly involved in producing knowledge about vaccination challenges. METHODS: We piloted a community-led ethnographic approach, training Community Health Workers (CHWs) in Kambia District, Sierra Leone, in qualitative social science methods. Methods included participant observation, participatory power mapping and rumour tracking, focus group discussions and key stakeholder interviews. CHWs, with the support of public health officials and professional social scientists, conducted research on vaccination challenges, analysed data, tested new community engagement strategies based on their findings and elicited local perspectives on these approaches. RESULTS: Our findings on vaccine confidence in five border communities highlighted three key themes: the impact of prior experiences with the health system on (mis)trust; relevance of livelihood strategies and power dynamics for vaccine uptake and access; and the contextual nature of knowledge around vaccines. Across these themes, we show how expressions of trust centered on social proximity, reliability and respect and the role of structural issues affecting both vaccine access and confidence. The pilot also highlighted the value and practical challenges to meaningfully co-designed research. CONCLUSION: There is scope for broader application of a community-led ethnographic approach will help redesign programming that is responsive to local knowledge and experience. Involving communities and low-cadre service providers in generating knowledge and solutions can strengthen relationships and sustain dialogue to bolster vaccine confidence.


Assuntos
Antropologia Cultural , Pesquisa Biomédica , Programas de Imunização , Características de Residência , Comportamento Social , Confiança , Vacinação , Grupos Focais , Pessoal de Saúde , Humanos , Serra Leoa , Vacinas/imunologia
4.
Am Fam Physician ; 104(4): 376-385, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34652097

RESUMO

Bioterrorism is the deliberate release of viruses, bacteria, toxins, or fungi with the goal of causing panic, mass casualties, or severe economic disruption. From 1981 to 2018, there were 37 bioterrorist attacks worldwide. The Centers for Disease Control and Prevention (CDC) lists anthrax, botulism, plague, smallpox, tularemia, and viral hemorrhagic fevers as category A agents that are the greatest risk to national security. An emerging infectious disease (e.g., novel respiratory virus) may also be used as a biological agent. Clinicians may be the first to recognize a bioterrorism-related illness by noting an unusual presentation, location, timing, or severity of disease. Public health authorities should be notified when a biological agent is recognized or suspected. Treatment includes proper isolation and administration of antimicrobial or antitoxin agents in consultation with regional medical authorities and the CDC. Vaccinations for biological agents are not routinely administered except for smallpox, anthrax, and Ebola disease for people at high risk of exposure. The American Academy of Family Physicians, the CDC, and other organizations provide bioterrorism training and response resources for clinicians and communities. Clinicians should be aware of bioterrorism resources.


Assuntos
Armas Biológicas , Bioterrorismo , Centers for Disease Control and Prevention, U.S. , Humanos , Estados Unidos , Vacinas/administração & dosagem , Vacinas/imunologia
5.
Cell Rep ; 37(2): 109823, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34610291

RESUMO

Although both infections and vaccines induce memory B cell (MBC) populations that participate in secondary immune responses, the MBCs generated in each case can differ. Here, we compare SARS-CoV-2 spike receptor binding domain (S1-RBD)-specific primary MBCs that form in response to infection or a single mRNA vaccination. Both primary MBC populations have similar frequencies in the blood and respond to a second S1-RBD exposure by rapidly producing plasmablasts with an abundant immunoglobulin (Ig)A+ subset and secondary MBCs that are mostly IgG+ and cross-react with the B.1.351 variant. However, infection-induced primary MBCs have better antigen-binding capacity and generate more plasmablasts and secondary MBCs of the classical and atypical subsets than do vaccine-induced primary MBCs. Our results suggest that infection-induced primary MBCs have undergone more affinity maturation than vaccine-induced primary MBCs and produce more robust secondary responses.


Assuntos
Vacinas contra COVID-19/imunologia , Plasmócitos/imunologia , SARS-CoV-2/imunologia , Adulto , Animais , Anticorpos Antivirais/imunologia , Subpopulações de Linfócitos B/imunologia , Linfócitos B/imunologia , COVID-19/imunologia , COVID-19/metabolismo , Reações Cruzadas/imunologia , Feminino , Células HEK293 , Humanos , Imunização/métodos , Memória Imunológica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , RNA Mensageiro/imunologia , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinação/métodos , Vacinas/imunologia
6.
Cells ; 10(9)2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34572004

RESUMO

Adaptive cellular immunity plays a major role in clearing microbial invasion of mucosal tissues in mammals. Following the clearance of primary pathogens, memory lymphocytes are established both systemically and locally at pathogen entry sites. Recently, resident memory CD8 T and B cells (TRM and BRM respectively), which are parked mainly in non-lymphoid mucosal tissues, were characterized and demonstrated to be essential for protection against secondary microbial invasion. Here we reviewed the current understanding of the cellular and molecular cues regulating CD8 TRM and BRM development, maintenance and function. We focused particularly on elucidating the role of a novel tissue-resident helper T (TRH) cell population in assisting TRM and BRM responses in the respiratory mucosa following viral infection. Finally, we argue that the promotion of TRH responses by future mucosal vaccines would be key to the development of successful universal influenza or coronavirus vaccines, providing long-lasting immunity against a broad spectrum of viral strains.


Assuntos
Linfócitos B/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunidade nas Mucosas , Memória Imunológica , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Humanos , Vacinas/imunologia
7.
Viruses ; 13(9)2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34578324

RESUMO

The pandemic of COVID-19 caused by SARS-CoV-2 infection continues to spread around the world. Vaccines that elicit protective immunity have reduced infection and mortality, however new viral variants are arising that may evade vaccine-induced immunity or cause disease in individuals who are unable to develop robust vaccine-induced responses. Investigating the role of viral variants in causing severe disease, evading vaccine-elicited immunity, and infecting vulnerable individuals is important for developing strategies to control the pandemic. Here, we report fourteen breakthrough infections of SARS-CoV-2 in vaccinated individuals with symptoms ranging from asymptomatic/mild (6/14) to severe disease (8/14). High viral loads with a median Ct value of 19.6 were detected in the nasopharyngeal specimens from subjects regardless of disease severity. Sequence analysis revealed four distinct virus lineages, including alpha and gamma variants of concern. Immunosuppressed individuals were more likely to be hospitalized after infection (p = 0.047), however no specific variant was associated with severe disease. Our results highlight the high viral load that can occur in asymptomatic breakthrough infections and the vulnerability of immunosuppressed individuals to post-vaccination infections by diverse variants of SARS-CoV-2.


Assuntos
COVID-19/epidemiologia , COVID-19/virologia , Hospedeiro Imunocomprometido , SARS-CoV-2 , Idoso , COVID-19/diagnóstico , COVID-19/imunologia , Feminino , Genoma Viral , Genômica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Vacinas/imunologia , Carga Viral
8.
J Immunol Methods ; 498: 113133, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34480950

RESUMO

The study of the effect of cryopreservation on the functionality of monocyte-derived dendritic cells (MDDCs) and dendritic cells (DCs) is essential for their use in different clinical applications such as DCs-based vaccines. Its full maturation and its optimal functionality are crucial for DCs based immunotherapy. In this study, we compared MDDCs derived from fresh and cryopreserved PBMCs in the aspects of phenotype and its effect on T cells at the level of proliferation and cytokine secretion. We pulsed MDDCs obtained from fresh and cryopreserved PBMCs with two different stimuli, CEF and SEA, and the expression maturation markers and cytokine secretion were analyzed. Our results showed that the cryopreservation had no effects in the phenotype of the MDDCs obtained, cell viability, maturation markers expression and/or cytokines secretion, independently whether MDDCs had been generated from fresh or cryopreserved PBMCs. Thus, this study suggests that the use of cryopreserved cells is a good method to keep the cells before use in immunotherapy, avoiding the variability within same individual due to severe blood draws. Even so, the interpretation and comparison of different results should be done considering the different cryopreservation techniques and assays, and their effects on PBMCs, specifically on MDDC and DC cells.


Assuntos
Diferenciação Celular , Criopreservação , Células Dendríticas/imunologia , Monócitos/imunologia , Vacinas/imunologia , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Células Dendríticas/metabolismo , Células Dendríticas/transplante , Estudos de Viabilidade , Citometria de Fluxo , Humanos , Ativação Linfocitária , Teste de Cultura Mista de Linfócitos , Fenótipo , Linfócitos T/imunologia , Linfócitos T/metabolismo
9.
Nutrients ; 13(9)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34579070

RESUMO

Deoxynivalenol (DON), a highly prevalent mycotoxin food contaminant, is known to have immunotoxic effects. In the current study, the potential of dietary interventions with specific mixtures of trans-galactosyl-oligosaccharides (TOS) to alleviate these effects were assessed in a murine influenza vaccination model. Vaccine-specific immune responses were measured in C57Bl/6JOlaHsd mice fed diets containing DON, TOS or a combination, starting 2 weeks before the first vaccination. The direct effects of TOS and its main oligosaccharide, 3'-galactosyl-lactose (3'-GL), on DON-induced damage were studied in Caco-2 cells, as an in vitro model of the intestinal epithelial barrier. Exposure to DON significantly reduced vaccine-specific immune responses and the percentages of Tbet+ Th1 cells and B cells in the spleen. DON significantly altered epithelial structure and integrity in the ileum and reduced the SCFA levels in the cecum. Adding TOS into DON-containing diets significantly improved vaccine-specific immune responses, restored the immune cell balance in the spleen and increased SCFA concentrations in the cecum. Incubating Caco-2 cells with TOS and 3'-GL in vitro further confirmed their protective effects against DON-induced barrier disruption, supporting immune modulation. Overall, dietary intervention with TOS can attenuate the adverse effects of DON on Th1-mediated immune responses and gut homeostasis. These beneficial properties might be linked to the high levels of 3'-GL in TOS.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Influenza Humana/imunologia , Leite Humano/química , Oligossacarídeos/farmacologia , Tricotecenos/imunologia , Trissacarídeos/farmacologia , Vacinação , Animais , Células CACO-2 , Ceco/efeitos dos fármacos , Dieta , Ácidos Graxos Voláteis/metabolismo , Feminino , Contaminação de Alimentos , Humanos , Intestinos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Micotoxinas/imunologia , Baço/efeitos dos fármacos , Células Th1/metabolismo , Vacinas/imunologia
10.
Expert Rev Vaccines ; 20(10): 1273-1290, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34550859

RESUMO

INTRODUCTION: Vaccination is so far the most effective way of eradicating infections. Rapidly emerging drug resistance against infectious diseases and chemotherapy-related toxicities in cancer warrant immediate vaccine development to save mankind. Subunit vaccines alone, however, fail to elicit sufficiently strong and long-lasting protective immunity against deadly pathogens. Nanoparticle (NP)-based delivery vehicles like microemulsions, liposomes, virosomes, nanogels, micelles and dendrimers offer promising strategies to overcome limitations of traditional vaccine adjuvants. Nanovaccines can improve targeted delivery, antigen presentation, stimulation of body's innate immunity, strong T cell response combined with safety to combat infectious diseases and cancers. Further, nanovaccines can be highly beneficial to generate effective immutherapeutic formulations against cancer. AREAS COVERED: This review summarizes the emerging nanoparticle strategies highlighting their success and challenges in preclinical and clinical trials in infectious diseases and cancer. It provides a concise overview of current nanoparticle-based vaccines, their adjuvant potential and their cellular delivery mechanisms. EXPERT OPINION: The nanovaccines (50-250 nm in size) are most efficient in terms of tissue targeting, prolonged circulation and preferential uptake by the professional APCs chiefly due to their small size. More rational designing, improved antigen loading, extensive functionalization and targeted delivery are some of the future goals of ideal nanovaccines.


Assuntos
Nanopartículas , Vacinação/métodos , Vacinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Antígenos/imunologia , Vacinas contra COVID-19/administração & dosagem , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Humanos , Tamanho da Partícula , Vacinas/imunologia
11.
Sci Rep ; 11(1): 17626, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475453

RESUMO

Antigen identification is an important step in the vaccine development process. Computational approaches including deep learning systems can play an important role in the identification of vaccine targets using genomic and proteomic information. Here, we present a new computational system to discover and analyse novel vaccine targets leading to the design of a multi-epitope subunit vaccine candidate. The system incorporates reverse vaccinology and immuno-informatics tools to screen genomic and proteomic datasets of several pathogens such as Trypanosoma cruzi, Plasmodium falciparum, and Vibrio cholerae to identify potential vaccine candidates (PVC). Further, as a case study, we performed a detailed analysis of the genomic and proteomic dataset of T. cruzi (CL Brenner and Y strain) to shortlist eight proteins as possible vaccine antigen candidates using properties such as secretory/surface-exposed nature, low transmembrane helix (< 2), essentiality, virulence, antigenic, and non-homology with host/gut flora proteins. Subsequently, highly antigenic and immunogenic MHC class I, MHC class II and B cell epitopes were extracted from top-ranking vaccine targets. The designed vaccine construct containing 24 epitopes, 3 adjuvants, and 4 linkers was analysed for its physicochemical properties using different tools, including docking analysis. Immunological simulation studies suggested significant levels of T-helper, T-cytotoxic cells, and IgG1 will be elicited upon administration of such a putative multi-epitope vaccine construct. The vaccine construct is predicted to be soluble, stable, non-allergenic, non-toxic, and to offer cross-protection against related Trypanosoma species and strains. Further, studies are required to validate safety and immunogenicity of the vaccine.


Assuntos
Biologia Computacional/métodos , Vacinas/imunologia , Vacinologia/métodos , Vacinas Bacterianas/imunologia , Doença de Chagas/imunologia , Doença de Chagas/prevenção & controle , Cólera/imunologia , Cólera/prevenção & controle , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Humanos , Malária Falciparum/imunologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/imunologia , Vacinas Protozoárias/imunologia , Trypanosoma cruzi/imunologia , Vibrio cholerae/imunologia
13.
Front Immunol ; 12: 711565, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335627

RESUMO

Extracellular vesicles (EVs) are released by most cell types as part of an intracellular communication system in crucial processes such as inflammation, cell proliferation, and immune response. However, EVs have also been implicated in the pathogenesis of several diseases, such as cancer and numerous infectious diseases. An important feature of EVs is their ability to deliver a wide range of molecules to nearby targets or over long distances, which allows the mediation of different biological functions. This delivery mechanism can be utilized for the development of therapeutic strategies, such as vaccination. Here, we have highlighted several studies from a historical perspective, with respect to current investigations on EV-based vaccines. For example, vaccines based on exosomes derived from dendritic cells proved to be simpler in terms of management and cost-effectiveness than dendritic cell vaccines. Recent evidence suggests that EVs derived from cancer cells can be leveraged for therapeutics to induce strong anti-tumor immune responses. Moreover, EV-based vaccines have shown exciting and promising results against different types of infectious diseases. We have also summarized the results obtained from completed clinical trials conducted on the usage of exosome-based vaccines in the treatment of cancer, and more recently, coronavirus disease.


Assuntos
COVID-19/imunologia , Vacinas Anticâncer/imunologia , Exossomos/imunologia , Vesículas Extracelulares/imunologia , Neoplasias/imunologia , SARS-CoV-2/fisiologia , Vacinas/imunologia , Animais , Ensaios Clínicos como Assunto , Humanos , Imunidade , Imunização
14.
Malays J Pathol ; 43(2): 203-217, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34448786

RESUMO

The coronavirus disease 2019 (COVID-19) is one of the biggest public health threats in the 21st century. Nearly every country in the world has been affected by COVID-19. The magnitude of the problem, with over 179 million confirmed cases and 3.8 million deaths worldwide, has driven researchers to search for vaccines to combat the disease. The discovery and development of a new vaccine, from the initial stage to the vaccine finally reaching the patients, usually take many years. However, given the urgency of the situation, many clinical trials on the COVID-19 vaccines have been conducted at extraordinary speed, whereas several vaccines against SARS-CoV-2 are being administered worldwide. This article gives an overview of the different types of COVID-19 vaccines, with a focus on those with promising results and are commonly used worldwide. It also gives an overview of herd immunity and discusses the challenges in achieving herd immunity through the global vaccination campaigns. Last but not least, some strategies that may be used to address these challenges are discussed.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Imunidade Coletiva/imunologia , Saúde Pública/estatística & dados numéricos , Vacinas/imunologia , Humanos , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Vacinas/farmacologia
15.
BMC Vet Res ; 17(1): 267, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372835

RESUMO

BACKGROUND: Vaccination plays an important role in feline healthcare as it is the most effective measure for prevention against feline infectious diseases. Therefore, it is important to know owners' opinion towards cats' vaccination and current veterinary practices in order to advice owners on the use of the correct vaccination protocol. This study aimed to investigate the proportion of cats regularly vaccinated and identify the main factors motivating cat owners' decisions related to vaccination in Italy. A questionnaire was disseminated online (mainly via social networks) to collect data regarding Italian cat owners' demographics, information about cats, factors regarding cats' vaccination, and veterinary-owner relationship. RESULTS: A total of 1264 owners participated in the survey and 1247 questionnaires were completed and statistically analyzed. The majority (91%; n = 1131) of cats were vaccinated and 80% (n = 998) had been vaccinated within the last 3 years. Age of 2-4 years old cats and the acquisition from a breeder or cat shop were significantly associated with vaccination within the last 3 years. Cats vaccinated but not within the last 3 years were significantly associated with cat's indoor lifestyle, cats' age ≥ 5 years old and low annual household income. Importance of vaccination cost, low annual household income and owners' job not related to healthcare was statistically associated with the lack of cat's vaccination. In addition, 86% of the owners took their cat regularly to veterinary clinics. Veterinarians play a significant role in owners' decision, and they are considered the most useful source of information about vaccination by 97% of owners. CONCLUSIONS: The high number of recently vaccinated cats suggests owner's attention towards feline vaccination and cat's health. The importance of veterinarian's advice along with the knowledge of factors associated to the unvaccinated status of cats may help veterinarians to grow owner's confidence and increase prevention of feline infectious diseases. However further investigations based on a more comprehensive sample of the general population are needed to confirm the results of this survey.


Assuntos
Doenças do Gato/prevenção & controle , Vacinação/veterinária , Vacinas/imunologia , Adulto , Animais , Gatos , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Internet , Itália , Masculino , Pessoa de Meia-Idade , Motivação , Propriedade , Inquéritos e Questionários , Vacinação/psicologia , Adulto Jovem
16.
Cells ; 10(7)2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34359911

RESUMO

Extracellular vesicles (EVs), comprising large microvesicles (MVs) and exosomes (EXs), play a key role in intercellular communication, both in physiological and in a wide variety of pathological conditions. However, the education of EV target cells has so far mainly been investigated as a function of EX cargo, while few studies have focused on the characterization of EV surface membrane molecules and the mechanisms that mediate the addressability of specific EVs to different cell types and tissues. Identifying these mechanisms will help fulfill the diagnostic, prognostic, and therapeutic promises fueled by our growing knowledge of EVs. In this review, we first discuss published studies on the presumed EV "delivery code" and on the combinations of the hypothesized EV surface membrane "sender" and "recipient" molecules that may mediate EV targeting in intercellular communication. Then we briefly review the main experimental approaches and techniques, and the bioinformatic tools that can be used to identify and characterize the structure and functional role of EV surface membrane molecules. In the final part, we present innovative techniques and directions for future research that would improve and deepen our understandings of EV-cell targeting.


Assuntos
Vesículas Extracelulares/metabolismo , Animais , Biomarcadores/metabolismo , Glicômica , Humanos , Modelos Biológicos , Proteômica , Vacinas/imunologia
17.
PLoS Pathog ; 17(7): e1009752, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34288976

RESUMO

Highly immunogenic exotoxins are used as carrier proteins because they efficiently improve the immunogenicity of polysaccharides. However, their efficiency with protein antigens remains unclear. In the current study, the candidate antigen PA0833 from Pseudomonas aeruginosa was fused to the α-hemolysin mutant HlaH35A from Staphylococcus aureus to form a HlaH35A-PA0833 fusion protein (HPF). Immunization with HPF resulted in increased PA0833-specific antibody titers, higher protective efficacy, and decreased bacterial burden and pro-inflammatory cytokine secretion compared with PA0833 immunization alone. Using fluorescently labeled antigens to track antigen uptake and delivery, we found that HlaH35A fusion significantly improved antigen uptake in injected muscles and antigen delivery to draining lymph nodes. Both in vivo and in vitro studies demonstrated that the increased antigen uptake after immunization with HPF was mainly due to monocyte- and macrophage-dependent macropinocytosis, which was probably the result of HPF binding to ADAM10, the Hla host receptor. Furthermore, a transcriptome analysis showed that several immune signaling pathways were activated by HPF, shedding light on the mechanism whereby HlaH35A fusion improves immunogenicity. Finally, the improvement in immunogenicity by HlaH35A fusion was also confirmed with two other antigens, GlnH from Klebsiella pneumoniae and the model antigen OVA, indicating that HlaH35A could serve as a universal carrier protein to improve the immunogenicity of protein antigens.


Assuntos
Antígenos de Bactérias/imunologia , Proteínas Hemolisinas/imunologia , Vacinas/imunologia , Células A549 , Animais , Exotoxinas/imunologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Células RAW 264.7 , Proteínas Recombinantes de Fusão/imunologia
18.
Front Immunol ; 12: 681328, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305913

RESUMO

Inducing antigen-specific tolerance is a promising treatment for preventing or reversing Type 1 diabetes (T1D). In contrast to a vaccine that induces immune responses against pathogens, a tolerogenic vaccine can suppress immunity against antigens causing diseases by administrating a mixture of self-antigens with an adjuvant that decreases the strength of antigen-specific response. Kynurenine (Kyn) is an endogenous substance that can inhibit the natural killer cell and T cell proliferation and promote the differentiation of naïve T cells into regulatory T cells (Tregs). In this study, we evaluated the efficacy of Kyn as a novel suppressive adjuvant. Kyn was co-immunized with GAD65 phage vaccine to induce Treg cells and tolerogenic responses for the prevention of T1D in NOD mouse model. Mice were subcutaneously immunized two times with 1011 Pfu (100µL,1012 Pfu/ml) GAD65 phage vaccine doses mixed with 200 µg of Kyn. Serum antibodies and cytokines were detected by ELISA and electrochemiluminescence, respectively. Flow cytometry assay was used to analyze DC and Treg. MTS was used for the analysis of spleen lymphocyte proliferation. RNA sequencing was used to investigate mRNA and miRNA expression profiles in spleen lymphocytes. Compared to GAD65 phage vaccine alone, co-immunization of Kyn and GAD65 phage vaccine resulted in the prevention of hyperglycemia in 60% of mice for at least one month. Further, Kyn enhances GAD65-specific Th2-mediated immune responses; regulates the Th1/Th2 imbalance and increases the secretion of Th2 cytokines and the number of CD4+CD25+Foxp3+T cells; suppresses DC maturation and GAD65-specific T lymphocyte proliferation. Moreover, we integrated Kyn related miRNA and mRNA expression profiles obtained from the spleen lymphocyte RNA-sequencing which was stimulated by Kyn in vitro. These data provide an important basis for understanding the mechanisms underlying Kyn as an immunosuppressive adjuvant which regulated the immune response. These findings suggest that Kyn can serve as an effective suppressive adjuvant candidate for Type 1 diabetes vaccines.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/prevenção & controle , Cinurenina/administração & dosagem , Vacinas/imunologia , Animais , Anticorpos/sangue , Anticorpos/imunologia , Biologia Computacional/métodos , Citocinas/metabolismo , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Imunização , Imunomodulação , Ativação Linfocitária , Contagem de Linfócitos , Camundongos , Vacinas/administração & dosagem
19.
J Immunol ; 207(2): 735-744, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34244296

RESUMO

Characterization of germinal center B and T cell responses yields critical insights into vaccine immunogenicity. Nonhuman primates are a key preclinical animal model for human vaccine development, allowing both lymph node (LN) and circulating immune responses to be longitudinally sampled for correlates of vaccine efficacy. However, patterns of vaccine Ag drainage via the lymphatics after i.m. immunization can be stochastic, driving uneven deposition between lymphoid sites and between individual LN within larger clusters. To improve the accurate isolation of Ag-exposed LN during biopsies and necropsies, we developed and validated a method for coformulating candidate vaccines with tattoo ink in both mice and pigtail macaques. This method allowed for direct visual identification of vaccine-draining LN and evaluation of relevant Ag-specific B and T cell responses by flow cytometry. This approach is a significant advancement in improving the assessment of vaccine-induced immunity in highly relevant nonhuman primate models.


Assuntos
Imunogenicidade da Vacina/imunologia , Linfonodos/imunologia , Vacinas/imunologia , Animais , Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Células Cultivadas , Feminino , Centro Germinativo/imunologia , Humanos , Imunização/métodos , Tinta , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tatuagem/métodos , Vacinação/métodos
20.
Acta Trop ; 222: 106033, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34224719

RESUMO

Sm28GST is one of the candidate antigens for Schistosoma mansoni vaccine. Already Sm28GST vaccine formulations have shown to be protective against S. mansoni infection. Currently, efforts have been put into finding an adjuvant to enhance the immunity induced by Sm28GST. In the present work, we investigated whether heat-killed Propionibacterium acnes can be served as a potential adjuvant for recombinant Sm28GST (rSm28GST) antigen. As the results showed, P. acnes successfully modulated the Th1 humoral immune response induced by rSm28GST. Stronger Th1 cytokines responses were also observed in mice immunized with P. acnes-adjuvanted rSm28GST. Immunization of mice with P. acnes-adjuvanted rSm28GST was able to reduce worm burden and hepatic egg burden by 54.20 and 73.61%. Reduced granuloma size and count, as well as improved liver histology, were seen in P. acnes-adjuvanted rSm28GST immunized mice. These data suggest that P. acnes may evoke a stronger rSm28GST-induced immune response, higher resistance to S. mansoni infection, and more profound protection against S. mansoni-induced liver damages.


Assuntos
Antígenos de Helmintos/imunologia , Glutationa Transferase/imunologia , Propionibacterium acnes , Esquistossomose mansoni , Vacinas/imunologia , Adjuvantes Imunológicos , Animais , Anticorpos Anti-Helmínticos , Temperatura Alta , Camundongos , Schistosoma mansoni/imunologia , Esquistossomose mansoni/prevenção & controle , Células Th1/imunologia
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