Peptide Vaccine Research Articles

Structural, functional, molecular docking analysis of a hypothetical protein from Talaromyces marneffei and its molecular dynamic simulation: an in-silico approach

Telaromyces marneffei (formerly Penicillium marneffei) is an endemic pathogenic fungus in Southern China and Southeast Asia. It can cause disease in patients with travel-related exposure to this organism and high morbidity and mortality in acquired immune deficiency syndrome (AIDS). In this study, we analyzed the structure and function of a hypothetical protein from T. marneffei using several bioinformatics tools and servers to unveil novel pharmacological targets and design a peptide vaccine against specific epitopes. A total of seven functional epitopes were screened on the protein, and ‘STGVDMWSV’ was the most antigenic, non-allergenic and non-toxic. Molecular docking showed stronger affinity between the CTL epitope ‘STGVDMWSV’ and the MHC I allele HLA-A*02:01, a higher docking score −234.98 kcal/mol, revealed stable interactions during a 100 ns molecular dynamic simulation. Overall, the results of this study revealed that this hypothetical protein is crucial for comprehending biochemical, physiological pathways and identifying novel therapeutic targets for human health. Communicated by Ramaswamy H. Sarma

H3K27M neoepitope vaccination in diffuse midline glioma induces B and T cell responses across diverse HLA loci of a recovered patient.

H3K27M, a driver mutation with T and B cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma with poor survival. We functionally dissect the immune response of one patient treated with an H3K27M peptide vaccine who subsequently entered complete remission. The vaccine robustly expanded class II human leukocyte antigen (HLA)-restricted peripheral H3K27M-specific T cells. Using functional assays, we characterized 34 clonally unique H3K27M-reactive T cell receptors and identified critical, conserved motifs in their complementarity-determining region 3 regions. Using detailed HLA mapping, we further demonstrate that diverse HLA-DQ and HLA-DR alleles present immunogenic H3K27M epitopes. Furthermore, we identified and profiled H3K27M-reactive B cell receptors from activated B cells in the cerebrospinal fluid. Our results uncover the breadth of the adaptive immune response against a shared clonal neoantigen across multiple HLA allelotypes and support the use of class II-restricted peptide vaccines to stimulate tumor-specific T and B cells harboring receptors with therapeutic potential.

Prediction of linear B-cell epitopes based on protein sequence features and BERT embeddings

Linear B-cell epitopes (BCEs) play a key role in the development of peptide vaccines and immunodiagnostic reagents. Therefore, the accurate identification of linear BCEs is of great importance in the prevention of infectious diseases and the diagnosis of related diseases. The experimental methods used to identify BCEs are both expensive and time-consuming and they do not meet the demand for identification of large-scale protein sequence data. As a result, there is a need to develop an efficient and accurate computational method to rapidly identify linear BCE sequences. In this work, we developed the new linear BCE prediction method LBCE-BERT. This method is based on peptide chain sequence information and natural language model BERT embedding information, using an XGBoost classifier. The models were trained on three benchmark datasets. The model was training on three benchmark datasets for hyperparameter selection and was subsequently evaluated on several test datasets. The result indicate that our proposed method outperforms others in terms of AUROC and accuracy. The LBCE-BERT model is publicly available at: https://github.com/Lfang111/LBCE-BERT.

RNA Origami Functions as a Self-Adjuvanted Nanovaccine Platform for Cancer Immunotherapy.

Peptide-based vaccines have been widely investigated in cancer immunotherapy. Despite their high specificity, safety, and low production cost, these vaccines have shown limited success in clinical studies, owing to their poor immunogenicity. Extensive efforts have been devoted to increasing the immunogenicity of peptide vaccines by mixing peptides with adjuvants and/or promoting their delivery to tumor-draining lymph nodes (TdLNs) for better antigen presentation by and maturation of dendritic cells. Among these efforts, the exploration of various nanoparticles has been at the forefront of the rational design and construction of peptide-based vaccines. Here, we present a nanovaccine platform that is built on a self-assembled RNA origami (RNA-OG) nanostructure. As previously reported, this RNA-OG nanostructure is a potent toll-like receptor (TLR)3 agonist. In addition, due to its robust synthesis and versatility in modification, RNA-OG could be readily linked to peptides of interest. Thus, these RNA-OG nanostructures function as adjuvanted nanocarriers to construct RNA-OG-peptide nanovaccines that are uniform in size, consistent in peptide loading, and highly stable. Here, we demonstrate that the assembled RNA-OG-peptide nanovaccines induced dendritic cell maturation, reduced tumor-mediated immunosuppression, and mobilized tumor-specific CD8+ T cell responses at the tumor site. Together, these actions led to the elicitation of an effective antitumor immunity that increased the survival of tumor-bearing mice. The combination of RNA-OG-based nanovaccines with the α-PD-1 immune checkpoint blockade further enhanced the immunity. Hence, our RNA-OG nanostructures represent a robust, simple, and highly effective platform to empower peptide-based vaccines for cancer immunotherapy.

A preliminary study of the immunogenic response of plant-derived multi-epitopic peptide vaccine candidate of Mycoplasma gallisepticum in chickens.

Mycoplasma gallisepticum (MG) is responsible for chronic respiratory disease in avian species, characterized by symptoms like respiratory rales and coughing. Existing vaccines for MG have limited efficacy and require multiple doses. Certain MG cytoadherence proteins (GapA, CrmA, PlpA, and Hlp3) play a crucial role in the pathogen's respiratory tract colonization and infection. Plant-based proteins and therapeutics have gained attention due to their safety and efficiency. In this study, we designed a 21.4-kDa multi-epitope peptide vaccine (MEPV) using immunogenic segments from cytoadherence proteins. The MEPV's effectiveness was verified through computational simulations. We then cloned the MEPV, introduced it into the plant expression vector pSiM24-eGFP, and expressed it in Nicotiana benthamiana leaves. The plant-produced MEPV proved to be immunogenic when administered intramuscularly to chickens. It significantly boosted the production of immunoglobulin Y (IgY)-neutralizing antibodies against cytoadherence protein epitopes in immunized chickens compared to that in the control group. This preliminary investigation demonstrates that the plant-derived MEPV is effective in triggering an immune response in chickens. To establish an efficient poultry health management system and ensure the sustainability of the poultry industry, further research is needed to develop avian vaccines using plant biotechnology.

FusionVAC22_01: A phase I clinical trial evaluating a DNAJB1-PRKACA fusion transcript-based peptide vaccine combined with immune checkpoint inhibition for fibrolamellar hepatocellular carcinoma and other tumor entities carrying the oncogenic driver fusion.

TPS580 Background: The DNAJB1-PRKACA fusion transcript is the driver of tumor pathogenesis in fibrolamellar hepatocellular carcinoma (FL-HCC) as well as in other tumor entities, e.g. oncocytic neoplasms of the pancreas and bile duct, thus representing a broad target for novel therapies in cancer. Recently, the DNAJB1-PRKACA fusion protein was identified as a source for HLA-presented neoepitopes that can be targeted by T-cell-based immunotherapy (Bauer et al. Nat. Commun., 2022). The DNAJB1-PRKACA fusion-derived neoepitope FusionVAC-22 is in silico predicted to bind to 1,290 HLA class II alleles and contains HLA class I ligands from 13 of the 20 most frequent HLA class I alleles that cover 93.8% of the world population with at least one HLA allotype, enabling the broad application of FusionVAC-22-based immunotherapies. The first application of FusionVAC-22-based peptide vaccines adjuvanted with the TLR1/2 agonist XS15 emulsified in Montanide ISA 51 VG in two FL-HCC patients was well tolerated and showed the induction of profound and long-lasting T-cell responses. Of note, T-cell responses were accompanied by progression-free survival of both patients for so far 32 months and 13 months, respectively. Methods: Based on these encouraging results, we established a Phase I open-label, multicentric clinical trial to evaluate the immunogenicity along with safety and toxicity, as well as first signs of efficacy of the FusionVAC-22 based peptide vaccine, combined with the immune checkpoint inhibitor (ICI) atezolizumab, in 20 patients with locally advanced or metastatic FL-HCC or other malignant diseases that carry the DNAJB1-PRKACA fusion transcript. Further, key eligibility criteria include the absence of autoimmune phenomena due to prior immunotherapy agents (≥ grade 3) as well as tissue or organ allografts. The FusionVAC-22-based peptide vaccine is applied twice in a 4-weekly interval with the opportunity of a booster vaccination after 11 months. Atezolizumab application starts on day 15 after first vaccination and is continued 4-weekly for 1 year, followed by a 6-month follow-up. The primary objectives of the trial are immunogenicity, in terms of induction of peptide specific T-cell responses until 28 days after second vaccination, as well as safety and toxicity of the peptide vaccine in combination with ICI. Safety assessment is based on the frequency of adverse events according to CTCAE v5.0. Clinical efficacy is determined by iRECIST assessment on imaging. Furthermore, disease control rate, quality of life as well as overall and progression free survival will be assessed. Clinical trial information: NCT05937295 .

In silico discovery of diagnostic/vaccine candidate antigenic epitopes and a multi-epitope peptide vaccine (NaeVac) design for the brain-eating amoeba Naegleria fowleri causing human meningitis

Naegleria fowleri, the brain-eating amoeba, is a free-living amoeboflagellate with three different life cycles (trophozoite, flagellated, and cyst) that lives in a variety of habitats around the world including warm freshwater and soil. It causes a disease called naegleriasis leading meningitis and primary amoebic meningoencephalitis (PAM) in humans. N. fowleri is transmitted through contaminated water sources such as insufficiently chlorinated swimming pool water or contaminated tap water, and swimmers are at risk. N. fowleri is found all over the world, and most infections were reported in both developed and developing countries with high mortality rates and serious clinical findings. Until now, there is no FDA approved vaccine and early diagnosis is urgent against this pathogen. In this study, by analyzing the N. fowleri vaccine candidate proteins (Mp2CL5, Nfa1, Nf314, proNP-A and proNP-B), it was aimed to discover diagnostic/vaccine candidate epitopes and to design a multi-epitope peptide vaccine against this pathogen. After the in silico evaluation, three prominent diagnostic/vaccine candidate epitopes (EAKDSK, LLPHIRILVY, and FYAKLLPHIRILVYS) with the highest antigenicities were discovered and a potentially highly immunogenic/antigenic multi-epitope peptide vaccine (NaeVac) was designed against the brain-eating amoeba N. fowleri causing human meningitis.

Perceptions of cancer prevention options for Lynch syndrome (LS) in a multi-national convenience sample.

77 Background: LS is among the most common cancer (CA) syndromes affecting 1:280 individuals and portends high lifetime CA risk. Clinical trials are currently evaluating whether frameshift peptide vaccination (FSPVAX) could reduce LS CA risk. FSPVAX enhances immune response to diverse FSP neoantigens in MSI-H tumors and has shown promising results in an MSH2-mutant mouse model and metastatic MSI-H CRC. However, negative public attitudes towards vaccination and evidence suggesting low uptake of ASA chemoprevention (CP) among patients with LS could undermine success of this novel therapy. Here, we benchmark attitudes towards FSPVAX for CA prevention against colonoscopy (COLO) and aspirin or NSAID chemoprevention (CP). Methods: The PREVENTLynchII survey (IRB 20-8014) was distributed electronically to 1) participants in the Fox Chase Cancer Center (FCCC) Risk Registry and 2) members of two online LS support groups. Patients were invited to complete the one-time survey after providing informed consent. Demographic and personal CA history were collected. Attitudes were measured on 9-point scales indicating low vs high agreement with belief statements: e.g. “Colonoscopy is a convenient way to lower my risk of LS-related CA.” Results: Overall 296 participants at FCCC, nationally, and internationally completed the survey. Median age was 52.6 years [23-78], 84% female, and 95% White. Affected genes included MLH1 (20.3%), MSH2/EPCAM (35.5%), MSH6 (28.7%), and PMS2 (15.5%). Use of CP was uncommon (32.1% and 5.1% respectively). Stratified analyses of COLO perceptions by sex, age, and personal history of CA showed no differences. Interestingly, US pts viewed ASA as more convenient than non-US, and with lower risk of side effects (p=0.007), but were no more likely to use or recommend CP. Compared to COLO, FSPVAX was overall viewed as more convenient, but side effect concerns were higher, and perceptions of efficacy were lower (all p<0.001), while compared to CP, FSPVAX was less convenient and fostered greater concerns about side effects, but was viewed as having higher potential preventive efficacy (all p<0.001). FSPVAX perceptions showed high variability: pts >50 (p=0.003) and CA pts (p=0.01) saw FSP as more convenient (p=0.003) than younger and unaffected pts. CA pts reported higher reassurance than unaffected (p=0.04), while those >50 were more likely to participate in an FSPVAX study (p=0.04). US pts perceived more side effect risk of FSPVAX than non-US (p=0.003). Conclusions: Concerns about ASA CP and FSPVAX convenience, side effects, and efficacy are common among US and international patients with LS. [Table: see text]

In silico evaluation of outer membrane protein S2 as a suitable vaccine candidate against Edwardsiella tarda infection of fish

AbstractObjectiveEdwardsiella tarda, the agent responsible for edwardsiellosis, is one of the primary emerging pathogens in fish aquaculture. The disease leads to significant economic loss for the farmers. Development of effective vaccines can minimize the disease burden.MethodsThe types of vaccinations that are currently at the center of the most significant research are subunit vaccines. Outer membrane proteins, which are a component of the bacteria, are very well known to be effective at stimulating immune responses in the host. In this study, the gene encoding for outer membrane protein S2 (OmpS2) of E. tarda was identified, cloned, and sequenced, followed by in silico analysis.ResultThe structure and subcellular localization of the protein were first confirmed. Homology modeling of the whole protein was performed, and the protein was checked for its eligibility as a vaccine candidate. This was followed by identifying antigenic sites, B‐cell epitopes, and cytotoxic T‐lymphocyte epitopes on OmpS2. We obtained a few distinct vaccine peptides from OmpS2. The complete genome of E. tarda was subjected to genome analysis to identify potential epitopes that would bind to the fish major histocompatibility complex molecule and elicit both humoral and cell‐mediated immune responses.ConclusionThis study provides valuable insights for consideration of OmpS2 as a potential vaccine candidate against E. tarda infection.

Construction of Peptide Vaccine Candidate Based on β-Cell Epitopes of Indonesian Monkeypox Virus (MPXV) Virulence Protein:A Reverse Vaccinology

Infection with a DNA virus called monkeypox virus (MPXV) in humans has been identified in the Congo since 1970. Antiviral drugs are not effective for preventing MPXV infection. MPXV infection cases in Indonesia are very low but MPXV has the potential to become a global pandemic so it is very important to do prevention such as vaccine development. This study aims to construct a B cell epitope-based peptide vaccine candidate in Indonesian MPXV through an in silico approach.The development of the MPXV vaccine can be performed through a computational approach for preliminary studies. In silico-based construction of vaccines using B cell epitopes, antigenicity, allergenicity, docking, and molecular dynamics analysis have been used by researchers and scientists in solving viral infection cases. We recommend Pep A and Pep D as vaccine candidates because they allow recognition by B cells, antigenic peptides, non-allergenic and non-toxin. Peptide vaccine candidate can trigger B-cell activation to produce IgM isotype-specific antibodies through BCR interaction. In summary, the results of this study can be used for an initial study of MPXV vaccine development in Indonesia.

Human serum albumin as the carrier to fabricate STING-activating peptide nanovaccine for antitumor immunotherapy

Tumor vaccines are emerging as one of the most promising therapeutic strategies for cancer treatment. With the advantages of low toxicity, convenient production and stable quality control, peptide vaccines have been widely used in preclinical and clinical trials involving various malignancies. However, when used alone, they still suffer from significant challenges including poor stability and immunogenicity as well as the low delivery efficiency, leading to limited therapeutic success. Herein, the STING-activating peptide nanovaccine based on human serum albumin (HSA) and biodegradable MnO2 was constructed, which can improve the stability and immunogenicity of antigenic peptides as well as facilitate their uptake by dendritic cells (DCs). Meanwhile, Mn2+ degraded from the nanovaccine can activate the STING pathway and further promote DCs maturation. In this way, the prepared nanovaccine can efficiently mediate T-cell immune responses, thereby exerting the effects of tumor prevention and therapy. Moreover, the prepared nanovaccine possesses the advantages of low cost, convenient preparation and good biocompatibility, showing great potential for practical applications.

Vaccine Molecule Design Based on Phage Display and Computational Modeling against Rhabdovirus.

Rhabdoviruses with rich species lead a variety of high lethality and rapid transmission diseases to plants and animals around the globe. Vaccination is one of the most effective approaches to prevent and control virus disease. However, the key antigenic epitopes of glycoprotein being used for vaccine development are unclear. In this study, fish-derived Abs are employed for a Micropterus salmoides rhabdovirus (MSRV) vaccine design by phage display and bioinformatics analysis. We constructed an anti-MSRV phage Ab library to screen Abs for glycoprotein segment 2 (G2) (G129-266). Four M13-phage-displayed Abs (Ab-5, Ab-7, Ab-8 and Ab-30) exhibited strong specificity to target Ag, and Ab-7 had the highest affinity with MSRV. Ab-7 (300 μg/ml) significantly increased grass carp ovary cell viability to 83.40% and significantly decreased the titer of MSRV. Molecular docking results showed that the key region of Ag-Ab interaction was located in 10ESQEFTTLTSH20 of G2. G2Ser11 and G2Gln12 were replaced with alanine, respectively, and molecular docking results showed that the Ag-Ab was nonbinding (ΔG > 0). Then, the peptide vaccine KLH-G210-20 was immunized to M. salmoides via i.p. injection. ELISA result showed that the serum Ab potency level increased significantly (p < 0.01). More importantly, the challenge test demonstrated that the peptide vaccine elicited robust protection against MSRV invasion, and the relative percentage survival reached 62.07%. Overall, this study proposed an approach for screening key epitope by combining phage display technology and bioinformatics tools to provide a reliable theoretical reference for the prevention and control of viral diseases.

Transplantable Murine Tumors in the Studies of Peptide Antitumor Vaccines.

Numerous studies have shown that antitumor vaccines based on synthetic peptides are safe and can induce both CD8+ and CD4+ tumor-specific T cell responses. However, clinical results are still scarce, and such approach to antitumor treatment has not gained a wide implication, yet. Recently, particular advances have been achieved due to tumor sequencing and the search for immunogenic neoantigens caused by mutations. One of the most important issues for peptide vaccines, along with the choice of optimal adjuvants and vaccination regimens, is the search for effective target antigens. Extensive studies of peptide vaccines, including those on murine models, are required to reveal the effective vaccine constructs. The review presents transplantable murine tumors with the detected peptides that showed antitumor efficacy as a vaccine compound.

Novel toxin-based mRNA vaccine against Clostridium perfringens using in silico approaches

Clostridium perfringens is a bacterium that causes gastrointestinal diseases in humans and animals. The several powerful toxins such as alpha toxin (CPA), beta toxin (CPB), enterotoxin (CPE), Epsilon toxin (ETX), and theta toxin, play a major role in its pathogenesis. Traditional vaccine development methods are time-consuming and costly. In silico approaches offer an alternative strategy for designing vaccines by analyzing biological data and predicting immunogenic peptides. In this study, computational tools were utilized to design a RNA vaccine targeting C. perfringens toxins. Toxin protein sequences were retrieved and their linear B-cell, MHCI, and MHCII binding epitopes were predicted. Allergenicity, toxigenicity, and IFN-γ induction were assessed to select non-allergenic, non-toxic, and IFN-γ-inducing epitopes. Molecular docking was performed to identify epitopes that fit within the binding cleft of MHC alleles. A final peptide vaccine construct was designed with selected epitopes separated by a linker sequence. The antigenicity and physicochemical properties of the vaccine were evaluated. Immune response simulation showed enhanced secondary and tertiary immune responses, increased levels of immunoglobulins, cytotoxic T lymphocytes, helper T lymphocytes, macrophage activity, and elevated levels IFN-γ and interleukin-2. Docking analysis was done to assess interactions between the vaccine structure and Toll-like receptors. Codon optimization was performed, and a final RNA vaccine construct was designed. The secondary structure of the RNA vaccine was predicted and validated. Overall, this study demonstrates the potential of in silico approaches for designing an RNA vaccine against C. perfringens toxins, contributing to improved prevention and control of associated diseases.

A novel intranasal peptide vaccine inhibits non-small cell lung cancer with KRAS mutation.

KRAS mutations occur commonly in the lung and can lead to the development of non-small cell lung cancer (NSCLC). While the mutated KRAS protein is a neoantigen, it usually does not generate an effective anti-tumor immune response on mucosal/epithelial surfaces. Despite this, mutated KRAS remains a potential target for immunotherapy since immune targeting of this protein in animal models has been effective at eliminating tumor cells. We attempted to develop a KRAS vaccine using mutated and wild-type KRAS peptides in combination with a nanoemulsion (NE) adjuvant. The efficacy of this approach was tested in an inducible mutant KRAS-mouse lung tumor model. Animals were immunized intranasally using NE with KRAS peptides. These animals had decreased CD4+FoxP3+ T cells in both lymph nodes and spleen. Immunized animals also showed higher IFN-γ and IL-17a levels to mutated KRAS that were produced by CD8+ T cells and enhancement in KRAS-specific Th1 and Th17 responses that persisted for 3 months after the last vaccination. Importantly, the immunized animals had significantly decreased tumor incidence compared to control animals. In conclusion, a mucosal approach to KRAS vaccination demonstrated the ability to induce local KRAS-specific immune responses in the lung and resulted in reduced tumor incidence.

Immunotherapy against gliomas

Gliomas represent the most frequent malignant primary brain tumors in adults. Despite multimodal treatment concepts involving surgery, irradiation and chemotherapy, the prognosis remains poor and they are incurable. Recent insights into the interactions between the immune system and the central nervous system as well as breakthroughs in the results of other cancer types have led to the fact that various immunotherapeutic approaches against gliomas have also been investigated and in some cases specifically developed. This article provides an overview of the current status of different immunotherapeutic concepts against gliomas, highlighting the advantages, disadvantages, and challenges. Additionally, it provides an overview of currently ongoing immunotherapeutic clinical trials in Germany and neighboring countries. Previous randomized studies on antibodies against programmed cell death protein1 (anti-PD1) immune checkpoint inhibition, viral treatment and peptide vaccination targeting the variantIII of the epidermal growth factor receptor (EGFRvIII) in glioblastomas were negative with respect to survival benefits. Conversely, other immunotherapeutic approaches, such as multivalent or driver mutation-based vaccinations, cytokine-based therapy and cell therapy, demonstrated arobust scientific foundation, with at least early studies showing promising safety and pharmacodynamic effects on the tumors. Currently, immunotherapies against gliomas should only be applied within the framework of well-designed clinical studies. There are still many knowledge gaps regarding the mechanisms of action and resistance of various immunotherapies. Accompanying translational research is essential to address these gaps and develop more effective therapies.

Prediction of the 3D conformation of a small peptide vaccine targeting Aβ42 oligomers.

The original etiology of Alzheimer's disease (AD) is the deposition of amyloid-beta (Aβ) proteins, which starts from the aggregation of the Aβ oligomers. The optimal therapeutic strategy targeting Aβ oligomer aggregation is the development of AD vaccines. Despite the fact that positive progress has been made for experimental attempts at AD vaccines, the physicochemical and even structural properties of these AD vaccines remain unclear. In this study, through immunoinformatic and molecular dynamics (MD) simulations, we first designed and simulated an alternative of vaccine TAPAS and found that the structure of the alternative can reproduce the 3D conformation of TAPAS determined experimentally. Meanwhile, immunoinformatic methods were used to analyze the physicochemical properties of TAPAS, including immunogenicity, antigenicity, thermal stability, and solubility, which confirm well the efficacy and safety of the vaccine, and validate the scheme reliability of immunoinformatic and MD simulations in designing and simulating the TAPAS vaccine. Using the same scheme, we predicted the 3D conformation of the optimized ACI-24 peptide vaccine, an Aβ peptide with the first 15 residues of Aβ42 (Aβ1-15). The vaccine was verified once to be effective against both full-length Aβ1-42 and truncated Aβ4-42 aggregates, but an experimental 3D structure was absent. We have also explored the immune mechanism of the vaccine at the molecular level and found that the optimized ACI-24 and its analogues can block the growth of either full-length Aβ1-42 or truncated Aβ4-42 pentamer by contacting the hydrophobic residues within the N-terminus and β1 region on the contact surface of either pentamer. Additionally, residues (D1, D7, S8, H13, and Q15) were identified as the key residues of the vaccine to contact either of the two Aβ oligomers. This work provides a feasible implementation scheme of immunoinformatic and MD simulations for the development of AD small peptide vaccines, validating the power of the scheme as a parallel tool to the experimental approaches and injecting molecular-level information into the understanding and design of anti-AD vaccines.

Humanized mouse model for vaccine evaluation: an overview.

Animal models are essential in medical research for testing drugs and vaccines. These models differ from humans in various respects, so their results are not directly translatable in humans. To address this issue, humanized mice engrafted with functional human cells or tissue can be helpful. We propose using humanized mice that support the engraftment of human hematopoietic stem cells (HSCs) without irradiation to evaluate vaccines that influence patient immunity. For infectious diseases, several types of antigens and adjuvants have been developed and evaluated for vaccination. Peptide vaccines are generally used for their capability to fight cancer and infectious diseases. Evaluation of adjuvants is necessary as they induce inflammation, which is effective for an enhanced immune response but causes adverse effects in some individuals. A trial can be done on humanized mice to check the immunogenicity of a particular adjuvant and peptide combination. Messenger RNA has also emerged as a potential vaccine against viruses. These vaccines need to be tested with human immune cells because they work by producing a particular peptide of the pathogen. Humanized mice with human HSCs that can produce both myeloid and lymphoid cells show a similar immune response that these vaccines will produce in a patient.

Immunomodulatory nanoparticles activate cytotoxic T cells for enhancement of the effect of cancer immunotherapy.

Cancer immunotherapy represents a promising targeted treatment by leveraging the patient's immune system or adoptive transfer of active immune cells to selectively eliminate cancer cells. Despite notable clinical successes, conventional immunotherapies face significant challenges stemming from the poor infiltration of endogenous or adoptively transferred cytotoxic T cells in tumors, immunosuppressive tumor microenvironment and the immune evasion capability of cancer cells, leading to limited efficacy in many types of solid tumors. Overcoming these hurdles is essential to broaden the applicability of immunotherapies. Recent advances in nanotherapeutics have emerged as an innovative tool to overcome these challenges and enhance the therapeutic potential of tumor immunotherapy. The unique biochemical and biophysical properties of nanomaterials offer advantages in activation of immune cells in vitro for cell therapy, targeted delivery, and controlled release of immunomodulatory agents in vivo. Nanoparticles are excellent carriers for tumor associated antigens or neoantigen peptides for tumor vaccine, empowering activation of tumor specific T cell responses. By precisely delivering immunomodulatory agents to the tumor site, immunoactivating nanoparticles can promote tumor infiltration of endogenous T cells or adoptively transferred T cells into tumors, to overcoming delivery and biological barriers in the tumor microenvironment, augmenting the immune system's ability to recognize and eliminate cancer cells. This review provides an overview of the current advances in immunotherapeutic approaches utilizing nanotechnology. With a focus on discussions concerning strategies to enhance activity and efficacy of cytotoxic T cells and explore the intersection of engineering nanoparticles and immunomodulation aimed at bolstering T cell-mediated immune responses, we introduce various nanoparticle formulations designed to deliver therapeutic payloads, tumor antigens and immunomodulatory agents for T cell activation. Diverse mechanisms through which nanoparticle-based approaches influence T cell responses by improving antigen presentation, promoting immune cell trafficking, and reprogramming immunosuppressive tumor microenvironments to potentiate anti-tumor immunity are examined. Additionally, the synergistic potential of combining nanotherapeutics with existing immunotherapies, such as immune checkpoint inhibitors and adoptive T cell therapies is explored. In conclusion, this review highlights emerging research advances on activation of cytotoxic T cells using nanoparticle agents to support the promises and potential applications of nanoparticle-based immunomodulatory agents for cancer immunotherapy.

Prediction of promiscuous multiepitope-based peptide vaccine against RdRp of rotavirus using immunoinformatics studies.

Rotavirus, a dsRNA virus in the Reoviridae family, shows a segmented genome. The VP1 gene encodes the RNA-dependent RNA polymerase (RdRp). This study aims to develop a multiepitope-based vaccine targeting RdRp using immunoinformatic approaches. In this study, 100 available nucleotide sequences of VP1-Rotavirus belonging to different strains across the world were retrieved from NCBI database. The selected sequences were aligned, and a global consensus sequence was developed by using CLC work bench. The study involved immunoinformatic approaches and molecular docking studies to reveal the promiscuous epitopes that can be eventually used as active vaccine candidates for Rotavirus. In total, 27 highly immunogenic, antigenic, and non-allergenic T-cell and B-cell epitopes were predicted for the Multiepitope vaccine (MEV) against rotavirus. It was also observed that MEV can prove to be effective worldwide due to its high population coverage, demonstrating the consistency of this vaccine. Moreover, there is a high docking interaction and immunological response with a binding score of -50.2 kcal/mol, suggesting the vaccine's efficacy. Toll-like receptors (TLRs) also suggest that the vaccine is physiologically and immunologically effective. Collectively, our data point to an effective MEV against rotavirus that can effectively reduce viral infections and improve the health status worldwide.