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1.
Biomed Res Int ; 2022: 4302625, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105928

RESUMO

Background: Worldwide, Neisseria gonorrhoeae-related sexually transmitted infections (STIs) continue to be of significant public health concern. This obligate-human pathogen has developed a number of defenses against both innate and adaptive immune responses during infection, some of which are mediated by the pathogen's proteins. Hence, the uncharacterized proteins of N. gonorrhoeae can be annotated to get insight into the unique functions of this organism related to its pathogenicity and to find a more efficient therapeutic target. Methods: In this study, a hypothetical protein (HP) of N. gonorrhoeae was chosen for analysis and an in-silico approach was used to explore various properties such as physicochemical characteristics, subcellular localization, secondary structure, 3D structures, and functional annotation of that HP. Finally, a molecular docking analysis was performed to design an epitope-based vaccine against that HP. Results: This study has identified the potential role of the chosen HP of N. gonorrhoeae in plasmid transfer, cell cycle control, cell division, and chromosome partitioning. Acidic nature, thermal stability, cytoplasmic localization of the protein, and some of its other physicochemical properties have also been identified through this study. Molecular docking analysis has demonstrated that one of the T cell epitopes of the protein has a significant binding affinity with the human leukocyte antigen HLA-B∗15 : 01. Conclusions: The in-silico characterization of this protein will help us understand molecular mechanism of action of N. gonorrhoeae and get an insight into novel therapeutic identification processes. This research will, therefore, enhance our knowledge to find new medications to tackle this potential threat to humankind.


Assuntos
Gonorreia , Neisseria gonorrhoeae , Epitopos de Linfócito T , Gonorreia/tratamento farmacológico , Humanos , Imunidade Humoral , Simulação de Acoplamento Molecular , Neisseria gonorrhoeae/genética
2.
Front Immunol ; 13: 981350, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059485

RESUMO

Background: SARS-CoV-2 vaccination has proven the most effective measure to control the COVID-19 pandemic. Booster doses are being administered with limited knowledge on their need and effect on immunity. Objective: To determine the duration of specific T cells, antibodies and neutralization after 2-dose vaccination, to assess the effect of a third dose on adaptive immunity and to explore correlates of protection against breakthrough infection. Methods: 12-month longitudinal assessment of SARS-CoV-2-specific T cells, IgG and neutralizing antibodies triggered by 2 BNT162b2 doses followed by a third mRNA-1273 dose in a cohort of 77 healthcare workers: 17 with SARS-CoV-2 infection prior to vaccination (recovered) and 60 naïve. Results: Peak levels of cellular and humoral response were achieved 2 weeks after the second dose. Antibodies declined thereafter while T cells reached a plateau 3 months after vaccination. The decline in neutralization was specially marked in naïve individuals and it was this group who benefited most from the third dose, which resulted in a 20.9-fold increase in neutralization. Overall, recovered individuals maintained higher levels of T cells, antibodies and neutralization 1 to 6 months post-vaccination than naïve. Seventeen asymptomatic or mild SARS-CoV-2 breakthrough infections were reported during follow-up, only in naïve individuals. This viral exposure boosted adaptive immunity. High peak levels of T cells and neutralizing antibodies 15 days post-vaccination associated with protection from breakthrough infections. Conclusion: Booster vaccination in naïve individuals and the inclusion of viral antigens other than spike in future vaccine formulations could be useful strategies to prevent SARS-CoV-2 breakthrough infections.


Assuntos
COVID-19 , Vacinas Virais , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Imunidade Humoral , Pandemias , SARS-CoV-2 , Vacinas Sintéticas , Vacinas de mRNA
3.
PLoS Pathog ; 18(9): e1010830, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36054264

RESUMO

Hundreds of millions of SARS-CoV-2 mRNA-LNP vaccine doses have already been administered to humans. However, we lack a comprehensive understanding of the immune effects of this platform. The mRNA-LNP-based SARS-CoV-2 vaccine is highly inflammatory, and its synthetic ionizable lipid component responsible for the induction of inflammation has a long in vivo half-life. Since chronic inflammation can lead to immune exhaustion and non-responsiveness, we sought to determine the effects of pre-exposure to the mRNA-LNP on adaptive immune responses and innate immune fitness. We found that pre-exposure to mRNA-LNPs or LNP alone led to long-term inhibition of the adaptive immune response, which could be overcome using standard adjuvants. On the other hand, we report that after pre-exposure to mRNA-LNPs, the resistance of mice to heterologous infections with influenza virus increased while resistance to Candida albicans decreased. The diminished resistance to Candida albicans correlated with a general decrease in blood neutrophil percentages. Interestingly, mice pre-exposed to the mRNA-LNP platform can pass down the acquired immune traits to their offspring, providing better protection against influenza. In summary, the mRNA-LNP vaccine platform induces long-term unexpected immunological changes affecting both adaptive immune responses and heterologous protection against infections. Thus, our studies highlight the need for more research to determine this platform's true impact on human health.


Assuntos
COVID-19 , Nanopartículas , Animais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Imunidade Humoral , Imunidade Inata , Inflamação , Lipídeos , Camundongos , RNA Mensageiro/genética , SARS-CoV-2
4.
BMC Infect Dis ; 22(1): 721, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36057544

RESUMO

BACKGROUND: Understanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and control strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months. METHODS: We established a cohort of 769 healthcare workers including healthy and infected with SARS-CoV-2 in northern Barcelona to determine the kinetics of the IgM against the nucleocapsid (N) and the IgG against the N and spike (S) of SARS-CoV-2 in infected healthcare workers. The study period was from 5 May 2020 to 11 November 2021.We used non-linear mixed models to investigate the kinetics of IgG and IgM measured at nine time points over 17 months from the date of diagnosis. The model included factors of time, gender, and disease severity (asymptomatic, mild-moderate, severe-critical) to assess their effects and their interactions. FINDINGS: 474 of the 769 participants (61.6%) became infected with SARS-CoV-2. Significant effects of gender and disease severity were found for the levels of all three antibodies. Median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease at day 270 after the diagnosis, while IgG(N and S) levels remained positive at least until days 450 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay with a rate depending on disease severity. IgG(S) levels remained relatively constant from day 15 over time. INTERPRETATION: IgM(N) and IgG(N, S) SARS-CoV-2 antibodies showed a heterogeneous kinetics over the 17 months. Only the IgG(S) showed a stable increase, and the levels and the kinetics of antibodies varied according to disease severity. The kinetics of IgM and IgG observed over a year also varied by clinical spectrum can be very useful for public health policies around vaccination criteria in adult population. FUNDING: Regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478).


Assuntos
COVID-19 , Adulto , Anticorpos Antivirais , COVID-19/epidemiologia , Pessoal de Saúde , Humanos , Imunidade Humoral , Imunoglobulina G , Imunoglobulina M , Pandemias , SARS-CoV-2 , Espanha/epidemiologia
5.
Sci Rep ; 12(1): 15447, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104370

RESUMO

The humoral and cellular immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon the coronavirus disease 2019 (COVID-19) vaccination remain to be clarified. Hence, we aimed to investigate the long-term chronological changes in SARS-CoV-2 specific IgG antibody, neutralizing antibody, and T cell responses during and after receiving the BNT162b2 vaccine. We performed serological, neutralization, and T cell assays among 100 hospital workers aged 22-73 years who received the vaccine. We conducted seven surveys up to 8 months after the second vaccination dose. SARS-CoV-2 spike protein-specific IgG (IgG-S) titers and T cell responses increased significantly following the first vaccination dose. The highest titers were observed on day 29 and decreased gradually until the end of the follow-up period. There was no correlation between IgG-S and T cell responses. Notably, T cell responses were detected on day 15, earlier than the onset of neutralizing activity. This study demonstrated that both IgG-S and T cell responses were detected before acquiring sufficient levels of SARS-CoV-2 neutralizing antibodies. These immune responses are sustained for approximately 6 to 10 weeks but not for 7 months or later following the second vaccination, indicating the need for the booster dose (i.e., third vaccination).


Assuntos
COVID-19 , Vacinas Virais , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Humanos , Imunidade Humoral , Imunoglobulina G , Estudos Longitudinais , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Linfócitos T , Vacinação
7.
Front Immunol ; 13: 941385, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091071

RESUMO

T follicular helper (Tfh) cells drive humoral immunity by facilitating B cell responses at the initial and recall phases. Recent studies have indicated the possible involvement of Tfh cells in the process of chronic inflammation. However, the functional role of Tfh cells in persistent immune settings remains unclear. Here, we report that CD4+CD8+ (double-positive, DP; CD3+CD4+CD8+CXCR5hiPD-1hi) Tfh cells, a subset of germinal-center-type Tfh cells, were abundantly present in the fibroinflammatory lesions of patients with immunoglobulin G4-related disease (IgG4-RD). Transcriptome analyses showed that these DP-Tfh cells in the lesions of IgG4-RD preferentially expressed signature genes characteristic of cytotoxic CD8+ T cells, such as Eomes, CRTAM, GPR56, and granzymes, in addition to CD70. Scatter diagram analyses to examine the relationships between tissue-resident lymphocytes and various clinical parameters revealed that the levels of DP-Tfh cells were inversely correlated to the levels of serum IgG4 and local IgG4-expressing (IgG4+) memory B cells (CD19+CD27+IgD-) in patients with IgG4-RD. Cell culture experiments using autologous tonsillar lymphocytes further suggested that DP-Tfh cells possess a poor B-cell helper function and instead regulate memory B cells. Since CD4+ (single positive, SP; CD3+CD4+CD8-CXCR5hiPD-1hi) Tfh cells differentiated into DP-Tfh cells under stimulation with IL-2 and IL-7 as assessed by in vitro experiments, these data imply that SP-Tfh cells are a possible origin of DP-Tfh cells under persistent inflammation. These findings highlight the potential feedback loop mechanism of Tfh cells in immune tolerance under chronic inflammatory conditions. Further studies on DP-Tfh cells may facilitate control of unresolved humoral responses in IgG4-RD pathological inflammation.


Assuntos
Doença Enxerto-Hospedeiro , Doença Relacionada a Imunoglobulina G4 , Linfócitos T CD8-Positivos , Humanos , Imunidade Humoral , Imunoglobulina G , Inflamação , Receptor de Morte Celular Programada 1 , Receptores CXCR5 , Células T Auxiliares Foliculares , Linfócitos T Auxiliares-Indutores
8.
Sci Rep ; 12(1): 15733, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36131132

RESUMO

Recent outbreaks of Zika virus (ZIKV) infection have highlighted the need for a better understanding of ZIKV-specific immune responses. The ZIKV envelope glycoprotein (EZIKV) is the most abundant protein on the virus surface and it is the main target of the protective immune response. EZIKV protein contains the central domain (EDI), a dimerization domain containing the fusion peptide (EDII), and a domain that binds to the cell surface receptor (EDIII). In this study, we performed a systematic comparison of the specific immune response induced by different EZIKV recombinant proteins (EZIKV, EDI/IIZIKV or EDIIIZIKV) in two mice strains. Immunization induced high titers of E-specific antibodies which recognized ZIKV-infected cells and neutralized the virus. Furthermore, immunization with EZIKV, EDI/IIZIKV and EDIIIZIKV proteins induced specific IFNγ-producing cells and polyfunctional CD4+ and CD8+ T cells. Finally, we identified 4 peptides present in the envelope protein (E1-20, E51-70, E351-370 and E361-380), capable of inducing a cellular immune response to the H-2Kd and H-2Kb haplotypes. In summary, our work provides a detailed assessment of the immune responses induced after immunization with different regions of the ZIKV envelope protein.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Linfócitos T CD8-Positivos/metabolismo , Imunidade Celular , Imunidade Humoral , Camundongos , Proteínas Recombinantes , Proteínas do Envelope Viral
9.
Front Immunol ; 13: 987984, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119111

RESUMO

The high genetic and antigenic variability of influenza virus and the repeated exposures of individuals to the virus over time account for the human immune responses toward this pathogen to continuously evolve during the lifespan of an individual. Influenza-specific immune memory to past strains has been shown to affect the immune responses to subsequent influenza strains and in turn to be changed itself through the new virus encounter. However, exactly how and to what extent this happens remains unclear. Here we studied pre-existing immunity against influenza A virus (IAV) by assessing IAV binding (IgG), neutralizing, and neuraminidase-specific antibodies to 5 different IAV strains in 180 subjects from 3 different age cohorts, adolescents, adults, and elderly, over a 5-year time span. In each age cohort, the highest neutralizing antibody titers were seen for a virus strain that circulated early in their life but the highest increase in titer was found for the most recent virus strains. In contrast, the highest IgG titers were seen against recent virus strains but the biggest increase in titer occurred against older strains. Significant increases in neutralizing antibody titers against a newly encountered virus strain were observed in all age cohorts demonstrating that pre-existing immunity did not hamper antibody induction. Our results indicate that the evolution of influenza-specific humoral immunity differs for rather cross-reactive virus-binding antibodies and more strain-specific neutralizing antibodies. Nevertheless, in general, our observations lend support to the antigenic seniority theory according to which the antibody response to influenza is broadened with each virus encounter, with the earliest encountered strain taking in the most senior and thus dominant position.


Assuntos
Vírus da Influenza A , Influenza Humana , Adolescente , Adulto , Idoso , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , Imunidade Humoral , Imunoglobulina G , Neuraminidase
10.
J Virol ; 96(17): e0097622, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-35938870

RESUMO

Humoral immune perturbations contribute to pathogenic outcomes in persons with HIV-1 infection (PWH). Gut barrier dysfunction in PWH is associated with microbial translocation and alterations in microbial communities (dysbiosis), and IgA, the most abundant immunoglobulin (Ig) isotype in the gut, is involved in gut homeostasis by interacting with the microbiome. We determined the impact of HIV-1 infection on the antibody repertoire in the gastrointestinal tract by comparing Ig gene utilization and somatic hypermutation (SHM) in colon biopsies from PWH (n = 19) versus age and sex-matched controls (n = 13). We correlated these Ig parameters with clinical, immunological, microbiome and virological data. Gene signatures of enhanced B cell activation were accompanied by skewed frequencies of multiple Ig Variable genes in PWH. PWH showed decreased frequencies of SHM in IgA and possibly IgG, with a substantial loss of highly mutated IgA sequences. The decline in IgA SHM in PWH correlated with gut CD4+ T cell loss and inversely correlated with mucosal inflammation and microbial translocation. Diminished gut IgA SHM in PWH was driven by transversion mutations at A or T deoxynucleotides, suggesting a defect not at the AID/APOBEC3 deamination step but at later stages of IgA SHM. These results expand our understanding of humoral immune perturbations in PWH that could have important implications in understanding mucosal immune defects in individuals with chronic HIV-1 infection. IMPORTANCE The gut is a major site of early HIV-1 replication and pathogenesis. Extensive CD4+ T cell depletion in this compartment results in a compromised epithelial barrier that facilitates the translocation of microbes into the underlying lamina propria and systemic circulation, resulting in chronic immune activation. To date, the consequences of microbial translocation on the mucosal humoral immune response (or vice versa) remains poorly integrated into the panoply of mucosal immune defects in PWH. We utilized next-generation sequencing approaches to profile the Ab repertoire and ascertain frequencies of somatic hypermutation in colon biopsies from antiretroviral therapy-naive PWH versus controls. Our findings identify perturbations in the Ab repertoire of PWH that could contribute to development or maintenance of dysbiosis. Moreover, IgA mutations significantly decreased in PWH and this was associated with adverse clinical outcomes. These data may provide insight into the mechanisms underlying impaired Ab-dependent gut homeostasis during chronic HIV-1 infection.


Assuntos
Trato Gastrointestinal , Infecções por HIV , Imunoglobulina A , Hipermutação Somática de Imunoglobulina , Disbiose , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/virologia , Infecções por HIV/genética , Infecções por HIV/imunologia , HIV-1 , Humanos , Imunidade Humoral , Imunoglobulina A/genética
11.
Virulence ; 13(1): 1446-1454, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35999776

RESUMO

Rabies is an important zoonotic disease caused by the rabies virus (RABV). Currently, no effective treatment is available for this condition. The prevention and control of rabies mainly depend on effective vaccination. Therefore, it is crucial to enhance the immune responses induced by the rabies vaccine. Virus neutralizing antibodies (VNA) induced by rabies vaccines are important for the clearance of RABV. Interleukin-25 (IL-25) has been demonstrated to activate T helper type 2 cells that contribute to humoral immune responses. The IL-25 gene was inserted into the genome of RABV, and the immunogenicity of recombinant RABV with IL-25 gene was investigated to develop more efficient rabies vaccines. Here, we found that the expression of IL-25 did not affect RABV production in vitro and pathogenicity in vivo. However, recombinant RABV expression of IL-25 induced a better VNA level than the parental virus in mice. In addition, expression of IL-25 enhanced the IgG1 level induced by RABV. Furthermore, mice immunized with recombinant RABV showed a higher survival rate and milder clinical signs than those immunized with the parent strain after challenge with CVS-11. Thus, these results showed that IL-25 could enhance the humoral immune responses induced by RABV, suggesting that IL-25 can be used as a viral vaccine adjuvant.


Assuntos
Vacinas Antirrábicas , Vírus da Raiva , Raiva , Animais , Anticorpos Antivirais , Imunidade Humoral , Interleucina-17/genética , Camundongos , Raiva/prevenção & controle , Vacinas Antirrábicas/genética , Vírus da Raiva/genética
12.
Immunity ; 55(9): 1732-1746.e5, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-35961317

RESUMO

Many immunocompromised patients mount suboptimal humoral immunity after SARS-CoV-2 mRNA vaccination. Here, we assessed the single-cell profile of SARS-CoV-2-specific T cells post-mRNA vaccination in healthy individuals and patients with various forms of immunodeficiencies. Impaired vaccine-induced cell-mediated immunity was observed in many immunocompromised patients, particularly in solid-organ transplant and chronic lymphocytic leukemia patients. Notably, individuals with an inherited lack of mature B cells, i.e., X-linked agammaglobulinemia (XLA) displayed highly functional spike-specific T cell responses. Single-cell RNA-sequencing further revealed that mRNA vaccination induced a broad functional spectrum of spike-specific CD4+ and CD8+ T cells in healthy individuals and patients with XLA. These responses were founded on polyclonal repertoires of CD4+ T cells and robust expansions of oligoclonal effector-memory CD45RA+ CD8+ T cells with stem-like characteristics. Collectively, our data provide the functional continuum of SARS-CoV-2-specific T cell responses post-mRNA vaccination, highlighting that cell-mediated immunity is of variable functional quality across immunodeficiency syndromes.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Linfócitos T CD8-Positivos , COVID-19/prevenção & controle , Humanos , Imunidade Humoral , RNA Mensageiro/genética , Síndrome , Vacinação , Proteínas do Envelope Viral
13.
J Exp Med ; 219(10)2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36006380

RESUMO

The SARS-CoV-2 pandemic prompted a global vaccination effort and the development of numerous COVID-19 vaccines at an unprecedented scale and pace. As a result, current COVID-19 vaccination regimens comprise diverse vaccine modalities, immunogen combinations, and dosing intervals. Here, we compare vaccine-specific antibody and memory B cell responses following two-dose mRNA, single-dose Ad26.COV.2S, and two-dose ChAdOx1, or combination ChAdOx1/mRNA vaccination. Plasma-neutralizing activity, as well as the magnitude, clonal composition, and antibody maturation of the RBD-specific memory B cell compartments, showed substantial differences between the vaccination regimens. While individual monoclonal antibodies derived from memory B cells exhibited similar binding affinities and neutralizing potency against Wuhan-Hu-1 SARS-CoV-2, there were significant differences in epitope specificity and neutralizing breadth against viral variants of concern. Although the ChAdOx1 vaccine was inferior to mRNA and Ad26.COV.2S in several respects, biochemical and structural analyses revealed enrichment in a subgroup of memory B cell neutralizing antibodies with distinct RBD-binding properties resulting in remarkable potency and breadth.


Assuntos
COVID-19 , Vacinas Virais , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Imunidade Humoral , RNA Mensageiro , SARS-CoV-2 , Vacinação
14.
Colloids Surf B Biointerfaces ; 218: 112746, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35961114

RESUMO

As an important ingredient of Chinese yam, Chinese yam polysaccharides have received wide attention for their remarkable adjuvant activity. Pickering emulsion is an attractive platform for the delivery of vaccines. Our previous study has demonstrated that the Chinese yam polysaccharides PLGA-stabilized Pickering emulsion (CYP-PPAS) is a potentially safe and efficient adjuvant to improve the immune response. In this work, we further investigate the adjuvant activity of CYP-PPAS on cellular immunity. In vitro, the CYP-PPAS increased antigen uptake efficiency by DCs. In vivo, CYP-PPAS triggered the recruitment of DCs and macrophages and subsequently facilitated DCs maturation and antigen migration to lymph nodes. Furthermore, CYP-PPAS induced a robust humoral response and Th1/Th2 immune response, enhanced the activation of CD4+ and CD8+ T lymphocyte subpopulations, and also promoted the activation of cytotoxic T lymphocyte response. As a result, the CYP-PPAS serves as a promising vaccine delivery system to induce robust humoral and cellular immunities against diseases.


Assuntos
Dioscorea , Vacinas , Adjuvantes Imunológicos/farmacologia , Animais , Antígenos , Emulsões , Imunidade Celular , Imunidade Humoral , Camundongos , Camundongos Endogâmicos BALB C , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polissacarídeos
15.
Sci Rep ; 12(1): 14275, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-35995986

RESUMO

Norovirus is a leading cause of epidemic acute gastroenteritis. More than 30 genotypes circulate in humans, some are common, and others are only sporadically detected. Here, we investigated whether serology can be used to determine which genotypes infect children. We established a multiplex protein microarray with structural and non-structural norovirus antigens that allowed simultaneous antibody testing against 30 human GI and GII genotypes. Antibody responses of sera obtained from 287 children aged < 1 month to 5.5 years were profiled. Most specific IgG and IgA responses were directed against the GII.2, GII.3, GII.4, and GII.6 capsid genotypes. While we detected antibody responses against rare genotypes, we found no evidence for wide circulation. We also detected genotype-specific antibodies against the non-structural proteins p48 and p22 in sera of older children. In this study, we show the age-dependent antibody responses to a broad range of norovirus capsid and polymerase genotypes, which will aid in the development of vaccines.


Assuntos
Infecções por Caliciviridae , Gastroenterite , Imunidade Humoral , Norovirus , Infecções por Caliciviridae/imunologia , Proteínas do Capsídeo/genética , Pré-Escolar , Europa (Continente) , Gastroenterite/imunologia , Gastroenterite/virologia , Genótipo , Humanos , Lactente , Norovirus/genética , Filogenia
16.
Int J Mol Sci ; 23(16)2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-36012556

RESUMO

This study aims to assess the potential association of MBL2 gene single nucleotide polymorphisms (SNPs) to Chlamydia trachomatis infection. We analysed a selected sample of 492 DNA and serum specimens from Dutch Caucasian women. Women were categorized into four groups of infection status based on the results of DNA and antibody tests for C. trachomatis: Ct-DNA+/IgG+, Ct-DNA+/IgG-, Ct-DNA-/IgG+, and Ct-DNA-/IgG-. We compared six MBL2 SNPs (-619G > C (H/L), -290G > C (Y/X), -66C > T (P/Q), +154C > T (A/D), +161A > G (A/B), and +170A > G (A/C)) and their respective haplotypes in relation to these different subgroups. The -619C (L) allele was less present within the Ct-DNA-/IgG+ group compared with the Ct-DNA-/IgG- group (OR = 0.49; 95% CI: 0.28-0.83), while the +170G (C) allele was observed more in the Ct-DNA+/IgG+ group as compared with the Ct-DNA-/IgG- group (OR = 2.4; 95% CI: 1.1-5.4). The HYA/HYA haplotype was more often present in the Ct-DNA-/IgG- group compared with the Ct-DNA+/IgG+ group (OR = 0.37; 95% CI: 0.16-0.87). The +170G (C) allele was associated with increased IgG production (p = 0.048) in C. trachomatis PCR-positive women. This study shows associations for MBL in immune reactions to C. trachomatis. We showed clear associations between MBL2 genotypes, haplotypes, and individuals' stages of C. trachomatis DNA and IgG positivity.


Assuntos
Infecções por Chlamydia , Imunidade Humoral , Lectina de Ligação a Manose , Anticorpos Antibacterianos , Infecções por Chlamydia/genética , Infecções por Chlamydia/imunologia , Chlamydia trachomatis , Feminino , Haplótipos , Humanos , Imunoglobulina G , Lectina de Ligação a Manose/genética , Países Baixos , Polimorfismo de Nucleotídeo Único
17.
Front Immunol ; 13: 904415, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990686

RESUMO

The neonatal immune system is distinct from the immune system of older individuals rendering neonates vulnerable to infections and poor responders to vaccination. Adjuvants can be used as tools to enhance immune responses to co-administered antigens. Antibody (Ab) persistence is mediated by long-lived plasma cells that reside in specialized survival niches in the bone marrow, and transient Ab responses in early life have been associated with decreased survival of plasma cells, possibly due to lack of survival factors. Various cells can secrete these factors and which cells are the main producers is still up for debate, especially in early life where this has not been fully addressed. The receptor BCMA and its ligand APRIL have been shown to be important in the maintenance of plasma cells and Abs. Herein, we assessed age-dependent maturation of a broad range of bone marrow accessory cells and their expression of the survival factors APRIL and IL-6. Furthermore, we performed a comparative analysis of the potential of 5 different adjuvants; LT-K63, mmCT, MF59, IC31 and alum, to enhance expression of survival factors and BCMA following immunization of neonatal mice with tetanus toxoid (TT) vaccine. We found that APRIL expression was reduced in the bone marrow of young mice whereas IL-6 expression was higher. Eosinophils, macrophages, megakaryocytes, monocytes and lymphocytes were important secretors of survival factors in early life but undefined cells also constituted a large fraction of secretors. Immunization and adjuvants enhanced APRIL expression but decreased IL-6 expression in bone marrow cells early after immunization. Furthermore, neonatal immunization with adjuvants enhanced the proportion of plasmablasts and plasma cells that expressed BCMA both in spleen and bone marrow. Enhanced BCMA expression correlated with enhanced vaccine-specific humoral responses, even though the effect of alum on BCMA was less pronounced than those of the other adjuvants at later time points. We propose that low APRIL expression in bone marrow as well as low BCMA expression of plasmablasts/plasma cells in early life together cause transient Ab responses and could represent targets to be triggered by vaccine adjuvants to induce persistent humoral immune responses in this age group.


Assuntos
Vacinas contra a Tuberculose , Tuberculose , Adjuvantes Imunológicos , Adjuvantes Farmacêuticos/metabolismo , Animais , Antígeno de Maturação de Linfócitos B/metabolismo , Medula Óssea , Sobrevivência Celular , Imunidade Humoral , Interleucina-6/metabolismo , Camundongos , Oligodesoxirribonucleotídeos/metabolismo , Plasmócitos , Toxoide Tetânico , Tuberculose/metabolismo
18.
Transpl Int ; 35: 10677, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35992746

RESUMO

Protection of adult kidney transplant recipients against SARS-CoV2 was shown to be strongly impaired owing to low reactogenicity of available vaccines. So far, data on vaccination outcomes in adolescents are scarce due to later vaccination approval for this age group. We therefore comprehensively analyzed vaccination-specific humoral-, T- and B-cell responses in kidney transplanted adolescents aged 12-18 years in comparison to healthy controls 6 weeks after standard two-dose BNT162b2 ("Comirnaty"; Pfizer/BioNTech) vaccination. Importantly, 90% (18/20) of transplanted adolescents showed IgG seroconversion with 75% (15/20) developing neutralizing titers. Still, both features were significantly diminished in magnitude compared to controls. Correspondingly, spike-specific B cells were quantitatively reduced and enriched for non-isotype-class-switched IgD+27+ memory cells in patients. Whereas spike specific CD4+ T cell frequencies were similar in both groups, cytokine production and memory differentiation were significantly impaired in transplant recipients. Although our data identify limitations in all arms of vaccine-specific immunity, the majority of our adolescent patients showed robust humoral responses despite antimetabolite-based treatment being associated with poor vaccination outcomes in adults.


Assuntos
COVID-19 , Transplante de Rim , Adolescente , Adulto , Anticorpos Antivirais , Vacina BNT162/administração & dosagem , Vacina BNT162/efeitos adversos , COVID-19/prevenção & controle , Humanos , Imunidade Humoral , Transplante de Rim/efeitos adversos , RNA Viral , SARS-CoV-2 , Vacinação , Vacinas Sintéticas , Vacinas de mRNA
19.
Front Immunol ; 13: 941243, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35935966

RESUMO

Despite the availability of improved antiviral therapies, infection with Hepatitis B virus (HBV) remains a3 significant health issue, as a curable treatment is yet to be discovered. Current HBV vaccines relaying on the efficient expression of the small (S) envelope protein in yeast and the implementation of mass vaccination programs have clearly contributed to containment of the disease. However, the lack of an efficient immune response in up to 10% of vaccinated adults, the controversies regarding the seroprotection persistence in vaccine responders and the emergence of vaccine escape virus mutations urge for the development of better HBV immunogens. Due to the critical role played by the preS1 domain of the large (L) envelope protein in HBV infection and its ability to trigger virus neutralizing antibodies, including this protein in novel vaccine formulations has been considered a promising strategy to overcome the limitations of S only-based vaccines. In this work we aimed to combine relevant L and S epitopes in chimeric antigens, by inserting preS1 sequences within the external antigenic loop of S, followed by production in mammalian cells and detailed analysis of their antigenic and immunogenic properties. Of the newly designed antigens, the S/preS116-42 protein assembled in subviral particles (SVP) showed the highest expression and secretion levels, therefore, it was selected for further studies in vivo. Analysis of the immune response induced in mice vaccinated with S/preS116-42- and S-SVPs, respectively, demonstrated enhanced immunogenicity of the former and its ability to activate both humoral and cellular immune responses. This combined activation resulted in production of neutralizing antibodies against both wild-type and vaccine-escape HBV variants. Our results validate the design of chimeric HBV antigens and promote the novel S/preS1 protein as a potential vaccine candidate for administration in poor-responders to current HBV vaccines.


Assuntos
Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Animais , Anticorpos Bloqueadores , Anticorpos Neutralizantes , Vacinas contra Hepatite B , Imunidade Humoral , Mamíferos , Camundongos , Camundongos Endogâmicos BALB C , Vacinas Sintéticas
20.
Int J Pharm ; 625: 122083, 2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-35934167

RESUMO

Maintaining structural integrity and enhancing stability of inactivated foot-and-mouth disease virus (iFMDV) antigen in adjuvants is crucial to ensure the vaccine potency. Unfortunately, formulation with most reported adjuvants leads to the accelerated dissociation of iFMDV into inactive pentamers. Here, an ionic liquid, i.e., choline and niacin ([Cho][Nic]), which was found to stabilize iFMDV against the acid- and thermo- induced dissociation in buffer solution, was applied to construct a novel oil-in-ionic liquid (o/IL) nanoemulsion adjuvant composed of [Cho][Nic], squalene, and Tween 80. The o/IL nanoemulsion formulated with iFMDV has a monodisperse diameter of 135.8 ± 40.4 nm. The thermostability and long-term stability of iFMDV were remarkably enhanced in o/IL nanoemulsion compared with that in the o/w emulsion without [Cho][Nic] and in the commercial Montanide ISA 206 adjuvant. The o/IL nanoemulsion exerted its adjuvant effects by improving the humoral immune responses. Immunization of o/IL nanoemulsion adjuvanted iFMDV induced specific IgG titers similar to that adjuvanted by Montanide ISA 206 and about 4-fold higher than the un-adjuvanted iFMDV, also promoted the activation of B lymphocytes and the secretion of interleukin-4 in the mice model. This [Cho][Nic]-based o/IL nanoemulsion can serve as a promising adjuvant platform for the foot-and-mouth disease vaccine.


Assuntos
Vírus da Febre Aftosa , Líquidos Iônicos , Vacinas Virais , Adjuvantes Imunológicos/química , Adjuvantes Farmacêuticos , Animais , Anticorpos Antivirais , Antígenos Virais , Imunidade Humoral , Camundongos , Óleo Mineral
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