Leveraging artificial intelligence in vaccine development: A narrative review.

Vaccine development stands as a cornerstone of public health efforts, pivotal in curbing infectious diseases and reducing global morbidity and mortality. However, traditional vaccine development methods are often time-consuming, costly, and inefficient. The advent of artificial intelligence (AI) has ushered in a new era in vaccine design, offering unprecedented opportunities to expedite the process. This narrative review explores the role of AI in vaccine development, focusing on antigen selection, epitope prediction, adjuvant identification, and optimization strategies. AI algorithms, including machine learning and deep learning, leverage genomic data, protein structures, and immune system interactions to predict antigenic epitopes, assess immunogenicity, and prioritize antigens for experimentation. Furthermore, AI-driven approaches facilitate the rational design of immunogens and the identification of novel adjuvant candidates with optimal safety and efficacy profiles. Challenges such as data heterogeneity, model interpretability, and regulatory considerations must be addressed to realize the full potential of AI in vaccine development. Integrating emerging technologies, such as single-cell omics and synthetic biology, promises to enhance vaccine design precision and scalability. This review underscores the transformative impact of AI on vaccine development and highlights the need for interdisciplinary collaborations and regulatory harmonization to accelerate the delivery of safe and effective vaccines against infectious diseases. [Abstract copyright: Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.

Leveraging artificial intelligence in vaccine development: A narrative review

Vaccine development stands as a cornerstone of public health efforts, pivotal in curbing infectious diseases and reducing global morbidity and mortality. However, traditional vaccine development methods are often time-consuming, costly, and inefficient. The advent of artificial intelligence (AI) has ushered in a new era in vaccine design, offering unprecedented opportunities to expedite the process. This narrative review explores the role of AI in vaccine development, focusing on antigen selection, epitope prediction, adjuvant identification, and optimization strategies. AI algorithms, including machine learning and deep learning, leverage genomic data, protein structures, and immune system interactions to predict antigenic epitopes, assess immunogenicity, and prioritize antigens for experimentation. Furthermore, AI-driven approaches facilitate the rational design of immunogens and the identification of novel adjuvant candidates with optimal safety and efficacy profiles. Challenges such as data heterogeneity, model interpretability, and regulatory considerations must be addressed to realize the full potential of AI in vaccine development. Integrating emerging technologies, such as single-cell omics and synthetic biology, promises to enhance vaccine design precision and scalability. This review underscores the transformative impact of AI on vaccine development and highlights the need for interdisciplinary collaborations and regulatory harmonization to accelerate the delivery of safe and effective vaccines against infectious diseases

Enterovirus specific anti-peptide antibodies

Enterovirus 71 (EV-71) is the main causative agent of hand, foot, and mouth disease (HFMD) which is generally regarded as a mild childhood disease. In recent years, EV71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in Asia. A formalin-inactivated EV71 whole virus vaccine has completed phase III trial in China but is currently unavailable clinically. The high cost of manufacturing and supply problems may limit practical implementations in developing countries. Synthetic peptides representing the native primary structure of the viral immunogen which is able to elicit neutralizing antibodies can be made readily and is cost effective. However, it is necessary to conjugate short synthetic peptides to carrier proteins to enhance their immunogenicity. This review describes the production of cross-neutralizing anti-peptide antibodies in response to immunization with synthetic peptides selected from in silico analysis, generation of B-cell epitopes of EV71 conjugated to a promiscuous T-cell epitope from Poliovirus, and evaluation of the neutralizing activities of the anti-peptide antibodies. Besides neutralizing EV71 in vitro, the neutralizing antibodies were cross-reactive against several Enteroviruses including CVA16, CVB4, CVB6, and ECHO13

POPISK: T-cell reactivity prediction using support vector machines and string kernels

BACKGROUND: Accurate prediction of peptide immunogenicity and characterization of relation between peptide sequences and peptide immunogenicity will be greatly helpful for vaccine designs and understanding of the immune system. In contrast to the prediction of antigen processing and presentation pathway, the prediction of subsequent T-cell reactivity is a much harder topic. Previous studies of identifying T-cell receptor (TCR) recognition positions were based on small-scale analyses using only a few peptides and concluded different recognition positions such as positions 4, 6 and 8 of peptides with length 9. Large-scale analyses are necessary to better characterize the effect of peptide sequence variations on T-cell reactivity and design predictors of a peptide's T-cell reactivity (and thus immunogenicity). The identification and characterization of important positions influencing T-cell reactivity will provide insights into the underlying mechanism of immunogenicity. RESULTS: This work establishes a large dataset by collecting immunogenicity data from three major immunology databases. In order to consider the effect of MHC restriction, peptides are classified by their associated MHC alleles. Subsequently, a computational method (named POPISK) using support vector machine with a weighted degree string kernel is proposed to predict T-cell reactivity and identify important recognition positions. POPISK yields a mean 10-fold cross-validation accuracy of 68% in predicting T-cell reactivity of HLA-A2-binding peptides. POPISK is capable of predicting immunogenicity with scores that can also correctly predict the change in T-cell reactivity related to point mutations in epitopes reported in previous studies using crystal structures. Thorough analyses of the prediction results identify the important positions 4, 6, 8 and 9, and yield insights into the molecular basis for TCR recognition. Finally, we relate this finding to physicochemical properties and structural features of the MHC-peptide-TCR interaction. CONCLUSIONS: A computational method POPISK is proposed to predict immunogenicity with scores which are useful for predicting immunogenicity changes made by single-residue modifications. The web server of POPISK is freely available at http://iclab.life.nctu.edu.tw/POPISK

Immunoinformatic identification of CD8+ T-cell epitopes

Antigen-specific T-cells play a crucial role in the adaptive immune response by providing a defence mechanism against pathogens and maintaining tolerance against self-antigens. This sparked interest in the development of epitope-based vaccines and immunotherapies that elicit antigen-specific T-cell responses. However, screening the antigens driving the response is currently labour-intensive, low-throughput and costly. Due to the limitations of experimental approaches, computational methods for predicting CD8+ T-cells have started to emerge. However, predicting the T-cell recognition potential of MHC-presented peptides has shown to be more challenging than predicting MHC ligands, and the full spectrum of features underlying peptide immunogenicity remains to be explored. Hence, this thesis presents a systems biology approach to study features of peptide immunogenicity and accurately predict CD8+ T-cell epitopes from HLA-I presented pathogenic or cancer peptides. The thesis begins with an immunoinformatic analysis of antigen-specific T-cell profiles in the contexts of autoinflammatory and infectious diseases. In autoinflammatory disease, the multi-modal single-cell sequencing of ulcerative colitis and checkpoint treatment-induced colitis revealed pathology-specific differential expressions of cytotoxic T-cells. The current technologies, however, were unable to identify the source antigen, emphasising the importance of predicting T-cell targets to better understand disease pathology. Moreover, in infectious diseases, CD8+ T-cell epitope prediction algorithms facilitated the understanding of disease heterogeneity and vaccine design during the COVID-19 pandemic, but many existing algorithms were found to be ill-suited for predicting epitopes from emerging pathogens. Therefore, a novel computational workflow was developed for an accurate and robust prediction of source antigens driving the cellular immune response. First, an unbiased evaluation of state-of-the-art algorithms revealed that they perform poorly on both cancer neoepitopes (e.g. glioblastoma) and pathogenic (e.g. SARS-CoV-2) epitopes. After investigating the reasons for low performance, TRAP, a deep learning workflow for context-specific prediction of CD8+ T-cell epitopes, was developed to effectively capture T-cell recognition motifs. The application of TRAP was demonstrated by using it to investigate the immune escape potential of all theoretical SARS-CoV-2 mutants. Thus, this thesis presents a novel computational platform for accurately predicting CD8+ T-cell epitopes to foster a better understanding of TCR:pMHC interaction and the development of effective clinical therapeutics

Machine-learning prediction of tumor antigen immunogenicity in the selection of therapeutic epitopes

Current tumor neoantigen calling algorithms primarily rely on epitope/major histocompatibility complex (MHC) binding affinity predictions to rank and select for potential epitope targets. These algorithms do not predict for epitope immunogenicity using approaches modeled from tumor-specific antigen data. Here, we describe peptide-intrinsic biochemical features associated with neoantigen and minor histocompatibility mismatch antigen immunogenicity and present a gradient boosting algorithm for predicting tumor antigen immunogenicity. This algorithm was validated in two murine tumor models and demonstrated the capacity to select for therapeutically active antigens. Immune correlates of neoantigen immunogenicity were studied in a pan-cancer data set from The Cancer Genome Atlas and demonstrated an association between expression of immunogenic neoantigens and immunity in colon and lung adenocarcinomas. Lastly, we present evidence for expression of an out-of-frame neoantigen that was capable of driving antitumor cytotoxic T-cell responses. With the growing clinical importance of tumor vaccine therapies, our approach may allow for better selection of therapeutically relevant tumor-specific antigens, including nonclas-sic out-of-frame antigens capable of driving antitumor immunity

The genome of the protozoan parasite Cystoisospora suis and a reverse vaccinology approach to identify vaccine candidates

Vaccine development targeting protozoan parasites remains challenging, partly due to the complex interactions between these eukaryotes and the host immune system. Reverse vaccinology is a promising approach for direct screening of genome sequence assemblies for new vaccine candidate proteins. Here, we applied this paradigm to Cystoisospora suis, an apicomplexan parasite that causes enteritis and diarrhea in suckling piglets and economic losses in pig production worldwide. Using Next Generation Sequencing we produced an ∼84 Mb sequence assembly for the C. suis genome, making it the first available reference for the genus Cystoisospora. Then, we derived a manually curated annotation of more than 11,000 protein-coding genes and applied the tool Vacceed to identify 1,168 vaccine candidates by screening the predicted C. suis proteome. To refine the set of candidates, we looked at proteins that are highly expressed in merozoites and specific to apicomplexans. The stringent set of candidates included 220 proteins, among which were 152 proteins with unknown function, 17 surface antigens of the SAG and SRS gene families, 12 proteins of the apicomplexan-specific secretory organelles including AMA1, MIC6, MIC13, ROP6, ROP12, ROP27, ROP32 and three proteins related to cell adhesion. Finally, we demonstrated in vitro the immunogenic potential of a C. suis-specific 42 kDa transmembrane protein, which might constitute an attractive candidate for further testing

Maximum n-times Coverage for Vaccine Design

We introduce the maximum $n$-times coverage problem that selects $k$ overlays to maximize the summed coverage of weighted elements, where each element must be covered at least $n$ times. We also define the min-cost $n$-times coverage problem where the objective is to select the minimum set of overlays such that the sum of the weights of elements that are covered at least $n$ times is at least $\tau$. Maximum $n$-times coverage is a generalization of the multi-set multi-cover problem, is NP-complete, and is not submodular. We introduce two new practical solutions for $n$-times coverage based on integer linear programming and sequential greedy optimization. We show that maximum $n$-times coverage is a natural way to frame peptide vaccine design, and find that it produces a pan-strain COVID-19 vaccine design that is superior to 29 other published designs in predicted population coverage and the expected number of peptides displayed by each individual's HLA molecules.Comment: 10 pages, 5 figure

Digital Orthopaedics: A Glimpse Into the Future in the Midst of a Pandemic.

BackgroundThe response to COVID-19 catalyzed the adoption and integration of digital health tools into the health care delivery model for musculoskeletal patients. The change, suspension, or relaxation of Medicare and federal guidelines enabled the rapid implementation of these technologies. The expansion of payment models for virtual care facilitated its rapid adoption. The authors aim to provide several examples of digital health solutions utilized to manage orthopedic patients during the pandemic and discuss what features of these technologies are likely to continue to provide value to patients and clinicians following its resolution.ConclusionThe widespread adoption of new technologies enabling providers to care for patients remotely has the potential to permanently change the expectations of all stakeholders about the way care is provided in orthopedics. The new era of Digital Orthopaedics will see a gradual and nondisruptive integration of technologies that support the patient's journey through the successful management of their musculoskeletal disease

Equivalent Mid-Term Results of Open vs Endoscopic Gluteal Tendon Tear Repair Using Suture Anchors in Forty-Five Patients.

BackgroundLittle is known about the relative efficacy of open (OGR) vs endoscopic (EGR) gluteal tendon repair of gluteal tendon tears in minimizing pain and restoring function. Our aim is to compare these 2 surgical techniques and quantify their impact on clinical outcomes.MethodsAll patients undergoing gluteal tendon tear repair at our institution between 2015 and 2018 were retrospectively reviewed. Pain scores, limp, hip abduction strength, and the use of analgesics were recorded preoperatively and at last follow-up. The Hip disability and Osteoarthritis Outcome Score Junior and Harris Hip Score Section1 were obtained at last follow-up. Fatty degeneration was quantified using the Goutallier-Fuchs Classification (GFC). Statistical analysis was conducted using one-way analysis of variance and t-tests.ResultsForty-five patients (mean age 66, 87% females) met inclusion criteria. Average follow-up was 20.3 months. None of the 10 patients (22%) undergoing EGR had prior surgery. Of 35 patients (78%) undergoing OGR, 12 (27%) had prior hip replacement (75% via lateral approach). The OGRs had more patients with GFC ≥2 (50% vs 11%, P = .02) and used more anchors (P = .03). Both groups showed statistical improvement (P ≤ .01) for all outcomes measured. GFC >2 was independently associated with a worst limp and Harris Hip Score Section 1 score (P = .05). EGR had a statistically higher opioid use reduction (P < .05) than OGR. Other comparisons between EGR and OGR did not reach statistical significance.ConclusionIn this series, open vs endoscopic operative approach did not impact clinical outcomes. More complex tears were treated open and with more anchors. Fatty degeneration adversely impacted outcomes. Although further evaluation of the efficacy of EGR in complex tears is indicated, both approaches can be used successfully