Doxorubicin-loaded Black Phosphorus Multifunctional Nanodelivery System Combined With Photothermal Therapy Promotes Immunogenic Death of Prostate Cancer PC-3 cells.

Prostate cancer is the second most harmful malignant tumor in men because of its insidious onset, easy metastasis, and easy development into castration-resistant prostate cancer even after treatment. Due to its high immunogenicity and a small number of specific infiltrating T cells with tumor-associated antigens in the tissue, it is difficult to obtain a good therapeutic effect with immune checkpoint blocking therapy alone. Therefore, in the current study, we developed a platform carrying Doxorubicin (DOX)-loaded black phosphate nanometer combined with photothermal therapy (PTT) and found this drug combination stimulated the immungentic cell death (ICD) process in PC-3 cells and DC maturation, allowing the DCs to present the related antigens and stimulate the body to produce more of CD8+ T cells, leading to a stronger immune response.More importantly, the introduction of Zn2+ and Aptamer (Apt) improved the prostate cancer cell killing ability of the nanosystem.

Generative Language Modeling for Antibody Design

Successful development of monoclonal antibodies (mAbs) for therapeutic applications is hindered by developability issues such as low solubility, low thermal stability, high aggregation, and high immunogenicity. The discovery of more developable mAb candidates relies on high-quality antibody libraries for isolating candidates with desirable properties. We present Immunoglobulin Language Model (IgLM), a deep generative language model for generating synthetic libraries by re-designing variable-length spans of antibody sequences. IgLM formulates antibody design as an autoregressive sequence generation task based on text-infilling in natural language. We trained IgLM on approximately 558M antibody heavy- and light-chain variable sequences, conditioning on each sequence's chain type and species-of-origin. We demonstrate that IgLM can be applied to generate synthetic libraries that may accelerate the discovery of therapeutic antibody candidates

Cross-Reactivity Conferred by Homologous and Heterologous Prime-Boost A/H5 Influenza Vaccination Strategies in Humans: A Literature Review

Avian influenza viruses from the A/H5 A/goose/Guangdong/1/1996 (GsGd) lineage pose a continuing threat to animal and human health. Since their emergence in 1997, these viruses have spread across multiple continents and have become enzootic in poultry. Additionally, over 800 cases of human infection with A/H5 GsGd viruses have been reported to date, which raises concerns about the potential for a new influenza virus pandemic. The continuous circulation of A/H5 GsGd viruses for over 20 years has resulted in the genetic and antigenic diversification of their hemagglutinin (HA) surface glycoprotein, which poses a serious challenge to pandemic preparedness and vaccine design. In the present article, clinical studies on A/H5 influenza vaccination strategies were reviewed to evaluate the breadth of antibody responses induced upon homologous and heterologous prime-boost vaccination strategies. Clinical data on immunological endpoints were extracted from studies and compiled into a dataset, which was used for the visualization and analysis of the height and breadth of humoral immune responses. Several aspects leading to high immunogenicity and/or cross-reactivity were identified, although the analysis was limited by the heterogeneity in study design and vaccine type used in the included studies. Consequently, crucial questions remain to be addressed in future studies on A/H5 GsGd vaccination strategies.

An Anhydrous Sodium Chloride Skin Preservation Model for Studies on Keratinocytes Grafting into the Wounds

Background. Human skin is needed for covering large body areas lost by trauma. The shortcomings of contemporary methods of skin storage are limited preservation time and high immunogenicity if allogeneic. Methods. We investigated whether long-lasting skin preservation in anhydrous sodium chloride (NaCl) may be the source of keratinocytes (KCs) for transplantation. Dehydrated skin fragments were preserved for a time frame from 1 week to 12 months. Then, skin fragments were rehydrated, and KCs were isolated. The viability of KCs was assessed in viability/cytotoxicity test. NaCl-preserved KCs were cultured for 7 days and transplanted to the dorsum of SCID mice. Results. The morphology of NaCl-preserved KCs was unaltered. KCs from all epidermal layers could be identified. All grafts were accepted by the recipients. Transplanted KCs: synthesized keratins 10 and 16 expressed antigens specific for stem cells and transient-amplifying cells, and remained HLA-I-positive. Moreover, they expressed the proliferative marker PCNA. Cells isolated from transplants remained viable and produced enzymes. Conclusions. Transplantation of KCs obtained from human skin and stored in anhydrous NaCl may be considered for the closure of extensive skin wounds. The originality of this method consists of an effective storage procedure and easy preparation of keratinocytes for transplantation.

Combined effects of glycan chain length and linkage type on the immunogenicity of glycoconjugate vaccines

The development and use of antibacterial glycoconjugate vaccines have significantly reduced the occurrence of potentially fatal childhood and adult diseases such as bacteremia, bacterial meningitis, and pneumonia. In these vaccines, the covalent linkage of bacterial glycans to carrier proteins augments the immunogenicity of saccharide antigens by triggering T cell-dependent B cell responses, leading to high-affinity antibodies and durable protection. Licensed glycoconjugate vaccines either contain long-chain bacterial polysaccharides, medium-sized oligosaccharides, or short synthetic glycans. Here, we discuss factors that affect the glycan chain length in vaccines and review the available literature discussing the impact of glycan chain length on vaccine efficacy. Furthermore, we evaluate the available clinical data on licensed glycoconjugate vaccine preparations with varying chain lengths against two bacterial pathogens, Haemophilus influenzae type b and Neisseria meningitidis group C, regarding a possible correlation of glycan chain length with their efficacy. We find that long-chain glycans cross-linked to carrier proteins and medium-sized oligosaccharides end-linked to carriers both achieve high immunogenicity and efficacy. However, end-linked glycoconjugates that contain long untethered stretches of native glycan chains may induce hyporesponsiveness by T cell-independent activation of B cells, while cross-linked medium-sized oligosaccharides may suffer from suboptimal saccharide epitope accessibility.

Evaluation of antibody response to BNT162b2 mRNA COVID-19 vaccine in patients affected by immune-mediated inflammatory diseases up to 5 months after vaccination

SARS-CoV-2 vaccination with mRNA product BNT162b2 elicited high immunogenicity in healthy subjects in trials. This study aims to better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs). We enrolled patients and healthy healthcare workers control group (HCW) that underwent mRNA BNT162b2 vaccination and measured the serum IgG anti-S-RBD response at booster dose (T1), one month after booster dose (T2) and up to 5 months (T3). Demographic, disease-specific and vaccination data were recorded. Vaccination response of 551 participants naïve to SARS-CoV-2 infection were included in HCW and 102 in the IMID group, analyzing separately those on anti-CD20. At T2 all naïve HCW developed anti-S-RBD-IgG, while 94% of IMID responded (p < 0.001). IMID patients had a significantly different level of IgG than HCW at both T1 (p = 0.031), T2 (p < 0.001), while there was no significant difference at T3. There were no statistically significant differences according to the IMID type or to ongoing treatment with immunosuppressants, corticosteroids or biological drugs other than anti-CD20. The proportion and magnitude of response was significantly lower in IMID treated with anti-CD20 drugs. There was a correlation with age at T1 and at T2 but not at T3, stronger in patients than in HCW. Immune response close after BNT162b2 vaccination is reduced in patients with IMID, but there is no significant difference at 5 months. The measured reduction is related to age and the disease itself rather than treatments, with the exception of anti-CD20 drugs.

Immunogenicity of a third dose viral-vectored COVID-19 vaccine after receiving two-dose inactivated vaccines in healthy adults

In June 2021, Thailand was hit by the delta variant of SARS-CoV-2 resulting in the biggest wave of COVID-19. Due to the widespread delta variant, more than 600 healthcare workers had COVID-19 despite completion of two-dose CoronaVac. The Ministry of Public Health recommended that healthcare workers received a third dose of AZD1222 to increase level of protection against SARS-CoV-2. However, immune response after the third vaccination with AZD1222 are limited. In this study, sera from those who received a booster of AZD1222 in June-July 2021 were tested for SARS-CoV-2 spike receptor-binding-domain (RBD) IgG, anti-RBD total immunoglobulins and anti-spike protein 1 (S1) IgA. The neutralizing activities in a subset of serum samples were tested against the wild type and variants of concern (B.1.1.7, B.1.617.2, and B.1.351) using an enzyme-linked immunosorbent assay-based surrogate virus neutralization test. Participants who received the booster of AZD1222 possessed higher levels of spike RBD-specific IgG, total immunoglobulins, and anti-S1 IgA than that two-dose vaccines (p < 0.001). They also elicited higher neutralizing activity against the wild type and all variants of concern than those in the recipients of the two-dose vaccines. This study demonstrated a high immunogenicity of the AZD1222 booster who completed the two-dose inactivated vaccines.

Prediction of protein venom epitope (kistomin) from Calloselasma rhodostoma using immunoinformatics to design vaccine based on epitope

accines based on epitope are alternative treatments for snakebite aside from anti-venom immunoglobulin, which is specific and not cross-reaction. However, the potential kistomin epitope has not been known. This study identified the region of T cells epitope and evaluated their immunogenicity to induce an immune response by in-silico. Sequences of kistomin were collected from Swiss-Prot with ID P0CB14. The physico-chemical and conserved domain of kistomin were predicted by using ProtParam and the NCBI database. The T cell epitope was predicted by using the Artificial Neural Network (ANN) method on the IEDB website. Epitopes with MHC-IC50 values more than 250 nM were further analyzed for conservation and immunogenicity on the IEDB website as well. After that, the candidate 9-mer epitope was interacted by simulated docking with four Major Histocompatibility Complex (MHC) molecules (5ENW, 6VB0, 3PGD, 6DIG). The conserved 9-mer epitope candidates with high immunogenicity and having similarities with the 15-mer epitope candidates are 4-VLLVTICLA-12 and 27-NVNDYEVVY-35. The 4-VLLVTICLA-12 candidate epitope interacted at β-sheet structure of four MHC. In contrast, The 27-NVNDYEVVY-35 candidate epitope interacted at α-helix and β-sheet structures of HLA-B*15:02 MHC. This study suggested 27-NVNDYEVVY-35 is potentially used as vaccine from envenomation Calloselasma rhodhostoma. In future studies, other alelles can be used to predict epitope from metalloproteinase domain in kistomin.

Comparative Immunogenicity of BNT162b2 mRNA Vaccine with Natural SARS-CoV-2 Infection

BNT162b2 has proven to be highly effective, but there is a paucity of data regarding immunogenicity factors and comparison between response to vaccination and natural infection. This study included 871 vaccinated healthcare workers (HCW) and 181 patients with natural infection. Immunogenicity was assessed by measuring anti-SARS-CoV-2 against the RBD domain of the spike protein (anti-RBD). Samples were collected 1–2 weeks after vaccination or 15–59 days post-onset of symptoms. Post-vaccine anti-RBD concentrations were associated with age, gender, vaccination side-effects (VSE) and prior infection (Pr-CoV). Anti-RBD median levels (95%CI) were lower by 2466 (651–5583), 6228 (3254–9203) and 7651 (4479–10,823) AU/mL in 35–44, 45–54, 55–70 yrs, respectively, compared with the 18–34 yrs group. In females, the median levels were higher by 2823 (859–4787), 5024 (3122–6926) in individuals with VSE, and 9971 (5158–14,783) AU/mL in HCWs with Pr-CoV. The ratio of anti-RBD in vaccinated individuals versus those with natural infection varied from 1.0 to 19.4. The high immunogenicity of BNT162b2 is verified, although its sustainability has yet to be elucidated. The use of comparative data from natural infection serological panels, expressing the clinical heterogeneity of natural infection, may facilitate early decisions for candidate vaccines to be evaluated in clinical trials.

Nanobodies Enhancing Cancer Visualization, Diagnosis and Therapeutics

Worldwide, cancer is a serious health concern due to the increasing rates of incidence and mortality. Conventional cancer imaging, diagnosis and treatment practices continue to substantially contribute to the fight against cancer. However, these practices do have some risks, adverse effects and limitations, which can affect patient outcomes. Although antibodies have been developed, successfully used and proven beneficial in various oncology practices, the use of antibodies also comes with certain challenges and limitations (large in size, poor tumor penetration, high immunogenicity and a long half-life). Therefore, it is vital to develop new ways to visualize, diagnose and treat cancer. Nanobodies are novel antigen-binding fragments that possess many advantageous properties (small in size, low immunogenicity and a short half-life). Thus, the use of nanobodies in cancer practices may overcome the challenges experienced with using traditional antibodies. In this review, we discuss (1) the challenges with antibody usage and the superior qualities of nanobodies; (2) the use of antibodies and nanobodies in cancer imaging, diagnosis, drug delivery and therapy (surgery, radiotherapy, chemotherapy and immunotherapy); and (3) the potential improvements in oncology practices due to the use of nanobodies as compared to antibodies.