protein antigen
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2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuma Sugiyama ◽  
Mitsuhiro Fujiwara ◽  
Akihiko Sakamoto ◽  
Hiromichi Tsushima ◽  
Akihiko Nishikimi ◽  
...  

Abstract Background Memory B cells are an antigen-experienced B-cell population with the ability to rapidly differentiate into antibody-producing cells by recall responses. We recently found that dedicator of cytokinesis 11 (DOCK11) contributes to the expansion of antigen-specific populations among germinal center B cells upon immunization. In comparison, limited information is available on the contribution of DOCK11 to secondary humoral immune responses. Results In this study, effects of the DOCK11 deficiency in B cells were examined on secondary immune responses to protein antigen. The lack of DOCK11 in B cells resulted in the impaired induction of antibody-producing cells upon secondary immunization with protein antigen. DOCK11 was dispensable for the recall responses of antigen-experienced B cells, as demonstrated by the comparable induction of antibody-producing cells in mice given transfer of antigen-experienced B cells with no DOCK11 expression. Instead, the lack of DOCK11 in B cells resulted in the impaired secondary immune responses in a B cell-extrinsic manner, which was recovered by the adoptive transfer of cognate T cells. Conclusions We addressed that intrinsic and extrinsic effects of DOCK11 expression in B cells may contribute to secondary humoral immune responses in manner of the induction of cognate T-cell help.


ACS Omega ◽  
2021 ◽  
Author(s):  
Marketa Svobodova ◽  
Vasso Skouridou ◽  
Miriam Jauset-Rubio ◽  
Irene Viéitez ◽  
Alberto Fernández-Villar ◽  
...  

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Timothy M. Caradonna ◽  
Aaron G. Schmidt

AbstractAntibody immunodominance refers to the preferential and asymmetric elicitation of antibodies against specific epitopes on a complex protein antigen. Traditional vaccination approaches for rapidly evolving pathogens have had limited success in part because of this phenomenon, as elicited antibodies preferentially target highly variable regions of antigens, and thus do not confer long lasting protection. While antibodies targeting functionally conserved epitopes have the potential to be broadly protective, they often make up a minority of the overall repertoire. Here, we discuss recent protein engineering strategies used to favorably alter patterns of immunodominance, and selectively focus antibody responses toward broadly protective epitopes in the pursuit of next-generation vaccines for rapidly evolving pathogens.


2021 ◽  
Vol 28 ◽  
Author(s):  
Nidia Cabral-Hipólito ◽  
Brenda Sarahí Molina-Ramírez ◽  
Irais Castillo-Maldonado ◽  
Rocío Meza-Velázquez ◽  
Rubén García-Garza ◽  
...  

Background: Immunization or vaccination is the process of inducing artificial immunity against an antigen taking advantage of the mechanisms of immunological memory. Current vaccines include substances known as adjuvants, which tend to improve the immunogenicity of the antigen, reduce the antigen quantity employed, and boost the immune response in weak responders. Unfortunately, only a few vaccine adjuvants are approved for human use. Objective: Thus, the objective of this study was to investigate the effect of Tannic acid on humoral and cell-mediated immunity against bovine serum albumin (BSA) as a protein antigen in Wistar rats. Method: In order to establish the Tannic acid concentration to test it as an adjuvant, the lethal dose 50 and maximum non-toxic dose were calculated through cytotoxicity and hemolytic assays with J774 A.1 cell line and rat erythrocytes by resazurin reduction method and UV/vis spectrophotometry. Thirty Wistar rats were divided into 5 groups that included two controls without antigen and three treatment groups of adjuvants plus BSA as a protein antigen. The rats were immunized in a 30-day scheme. Blood samples were collected for humoral immunity analysis by means of immunoglobulin quantification, isotyping and antigen-antibody precipitation inhibition analysis. Rat peritoneal macrophages and splenocytes were isolated for cell-mediated immunity analysis by means of nitric oxide quantification from adjuvant stimulated peritoneal macrophages and lymphocytes proliferation assay. Results: Tannic acid was capable of increasing the immunogenicity of the antigen; besides, it was able to stimulate cell-mediated immunity by means of increased lymphocyte proliferation. Moreover, Tannic acid improved the humoral response by means of increased specific antibodies titers. These activities may be attributed to pattern recognition receptors stimulation. Conclusion: Tannic acid was considered biocompatible when tested in vivo because the concentration tested did not show cytotoxicity or hemolytic effect, and there was no detrimental effect observed on the animals’ health. These results show Tannic acid as a promising candidate for vaccine adjuvant.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Myungjin Lee ◽  
Anita Changela ◽  
Jason Gorman ◽  
Reda Rawi ◽  
Tatsiana Bylund ◽  
...  

AbstractAntibody-Framework-to-Antigen Distance (AFAD) – the distance between the body of an antibody and a protein antigen – is an important parameter governing antibody recognition. Here, we quantify AFAD for ~2,000 non-redundant antibody-protein-antigen complexes in the Protein Data Bank. AFADs showed a gaussian distribution with mean of 16.3 Å and standard deviation (σ) of 2.4 Å. Notably, antibody-antigen complexes with extended AFADs (>3σ) were exclusively human immunodeficiency virus-type 1 (HIV-1)-neutralizing antibodies. High correlation (R2 = 0.8110) was observed between AFADs and glycan coverage, as assessed by molecular dynamics simulations of the HIV-1-envelope trimer. Especially long AFADs were observed for antibodies targeting the glycosylated trimer apex, and we tested the impact of introducing an apex-glycan hole (N160K); the cryo-EM structure of the glycan hole-targeting HIV-1-neutralizing antibody 2909 in complex with an N160K-envelope trimer revealed a substantially shorter AFAD. Overall, extended AFADs exclusively recognized densely glycosylated surfaces, with the introduction of a glycan hole enabling closer recognition.


Vaccine ◽  
2021 ◽  
Author(s):  
Wang Long ◽  
Shinji Kunitake ◽  
Shin-ichi Sawada ◽  
Kazunari Akiyoshi ◽  
Takeshi Tsubata

2021 ◽  
Vol 12 ◽  
Author(s):  
Mareike Rentzsch ◽  
Robert Wawrzinek ◽  
Claudia Zelle-Rieser ◽  
Helen Strandt ◽  
Lydia Bellmann ◽  
...  

Immune modulating therapies and vaccines are in high demand, not least to the recent global spread of SARS-CoV2. To achieve efficient activation of the immune system, professional antigen presenting cells have proven to be key coordinators of such responses. Especially targeted approaches, actively directing antigens to specialized dendritic cells, promise to be more effective and accompanied by reduced payload due to less off-target effects. Although antibody and glycan-based targeting of receptors on dendritic cells have been employed, these are often expensive and time-consuming to manufacture or lack sufficient specificity. Thus, we applied a small-molecule ligand that specifically binds Langerin, a hallmark receptor on Langerhans cells, conjugated to a model protein antigen. Via microneedle injection, this construct was intradermally administered into intact human skin explants, selectively loading Langerhans cells in the epidermis. The ligand-mediated cellular uptake outpaces protein degradation resulting in intact antigen delivery. Due to the pivotal role of Langerhans cells in induction of immune responses, this approach of antigen-targeting of tissue-resident immune cells offers a novel way to deliver highly effective vaccines with minimally invasive administration.


2021 ◽  
Vol 11 (4) ◽  
pp. 275-282
Author(s):  
In Bum Suh ◽  
Hana Kim ◽  
Chae Eun Kim ◽  
MSc ◽  
Jong-Chan Park ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254628
Author(s):  
Yasunari Haseda ◽  
Lisa Munakata ◽  
Chiyo Kimura ◽  
Yumi Kinugasa-Katayama ◽  
Yasuko Mori ◽  
...  

Most current clinical vaccines work primarily by inducing the production of neutralizing antibodies against pathogens. Vaccine adjuvants that efficiently induce T cell responses to protein antigens need to be developed. In this study, we developed a new combination adjuvant consisting of 1,2-dioleoyl-3-trimethylammonium propane (DOTAP), D35, and an aluminum salt. Among the various combinations tested, the DOTAP/D35/aluminum salt adjuvant induced strong T cell and antibody responses against the model protein antigen with a single immunization. Adjuvant component and model antigen interaction studies in vitro also revealed that the strong mutual interactions among protein antigens and other components were one of the important factors for this efficient immune induction by the novel combination adjuvant. In addition, in vivo imaging of the antigen distribution suggested that the DOTAP component in the combination adjuvant formulation elicited transient antigen accumulation at the draining lymph nodes, possibly by antigen uptake DC migration. These results indicate the potential of the new combination adjuvant as a promising vaccine adjuvant candidate to treat infectious diseases and cancers.


2021 ◽  
Vol 8 ◽  
Author(s):  
Qiaoling Deng ◽  
Guangming Ye ◽  
Yunbao Pan ◽  
Wen Xie ◽  
Gui Yang ◽  
...  

Objectives: COVID-19 emerged and rapidly spread throughout the world. Testing strategies focussing on patients with COVID-19 require assays that are high-throughput, low-risk of infection, and with small sample volumes. Antigen surveillance can be used to identify exposure to pathogens and measure acute infections.Methods: A total of 914 serum samples, collected from 309 currently infected COVID-19 patients, 48 recovered ones, and 410 non-COVID-19 patients, were used to measure N protein antigen levels by a chemilumineseent immunoassay. Diagnostic performances were analyzed in different periods after onset.Results: There was a high level of N protein antigen in COVID-19 patients (0.56 COI), comparing to the recovered patients (0.12 COI) and controls (0.19 COI). In receiver-operating characteristic curve analysis, the area under the curve of serum N protein antigen was 0.911 in the first week after onset. In this period, Sensitivity and specificity of serologic N protein antigen testing was 76.27 and 98.78%. Diagnosis performance of specific antibodies became better from the third week after onset. Subgroup analysis suggested that severe patients had higher levels of antigens than mild patients.Conclusions: High level of serum antigen suggested early infection and serious illness. Serum N protein antigen testing by chemiluminescence immunoassay is considered as a viable assay used to improve diagnostic sensitivity for current patients.


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