COVID-19 vaccine design using reverse and structural vaccinology, ontology-based literature mining and machine learning

Huffman, Anthony; Ong, Edison; Hur, Junguk; D’Mello, Adonis; Tettelin, Hervé; He, Yongqun

doi:10.1093/bib/bbac190

Cited by 11 publications

(5 citation statements)

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“…As more parasite vaccines are now advancing through clinical trials, such as the R21/matrix-M malaria vaccine [ 34 ], the number of known parasite protective antigens will increase. Furthermore, we are developing new machine learning or reverse vaccinology methods [ 35 , 36 ] to support parasite vaccine design. The newly collected and annotated parasite vaccine results will provide good training data for our method development.…”

Section: Discussionmentioning

confidence: 99%

Ontological representation, modeling, and analysis of parasite vaccines

Huffman,

Zhang,

Lanka

et al. 2024

J Biomed Semant

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Background Pathogenic parasites are responsible for multiple diseases, such as malaria and Chagas disease, in humans and livestock. Traditionally, pathogenic parasites have been largely an evasive topic for vaccine design, with most successful vaccines only emerging recently. To aid vaccine design, the VIOLIN vaccine knowledgebase has collected vaccines from all sources to serve as a comprehensive vaccine knowledgebase. VIOLIN utilizes the Vaccine Ontology (VO) to standardize the modeling of vaccine data. VO did not model complex life cycles as seen in parasites. With the inclusion of successful parasite vaccines, an update in parasite vaccine modeling was needed. Results VIOLIN was expanded to include 258 parasite vaccines against 23 protozoan species, and 607 new parasite vaccine-related terms were added to VO since 2022. The updated VO design for parasite vaccines accounts for parasite life stages and for transmission-blocking vaccines. A total of 356 terms from the Ontology of Parasite Lifecycle (OPL) were imported to VO to help represent the effect of different parasite life stages. A new VO class term, ‘transmission-blocking vaccine,’ was added to represent vaccines able to block infectious transmission, and one new VO object property, ‘blocks transmission of pathogen via vaccine,’ was added to link vaccine and pathogen in which the vaccine blocks the transmission of the pathogen. Additionally, our Gene Set Enrichment Analysis (GSEA) of 140 parasite antigens used in the parasitic vaccines identified enriched features. For example, significant patterns, such as signal, plasma membrane, and entry into host, were found in the antigens of the vaccines against two parasite species: Plasmodium falciparum and Toxoplasma gondii. The analysis found 18 out of the 140 parasite antigens involved with the malaria disease process. Moreover, a majority (15 out of 54) of P. falciparum parasite antigens are localized in the cell membrane. T. gondii antigens, in contrast, have a majority (19/24) of their proteins related to signaling pathways. The antigen-enriched patterns align with the life cycle stage patterns identified in our ontological parasite vaccine modeling. Conclusions The updated VO modeling and GSEA analysis capture the influence of the complex parasite life cycles and their associated antigens on vaccine development.

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Section: Discussionmentioning

confidence: 99%

Ontological representation, modeling, and analysis of parasite vaccines

Huffman,

Zhang,

Lanka

et al. 2024

J Biomed Semant

Self Cite

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“…Nevertheless, undeniably, safe vaccines will be needed. May reverse vaccinology favorably contribute to inducing short-term immunity for future pathogens [ 71 , 72 , 73 , 74 , 75 ]. The short-lasting presence of antibodies may prevent the phenomenon of antibody-dependent enhancement (ADE) and even false test results.…”

Section: From Current To Future Coming Public Health and The Molecula...mentioning

confidence: 99%

The Deceptive COVID-19: Lessons from Common Molecular Diagnostics and a Novel Plan for the Prevention of the Next Pandemic

Mouliou¹

2023

Diseases

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The COVID-19 pandemic took place during the years 2020–2022 and the virus, named SARS-CoV-2, seems likely to have resulted in an endemic disease. Nevertheless, widespread COVID-19 has given rise to several major molecular diagnostics’ facts and concerns that have emerged during the overall management of this disease and the subsequent pandemic. These concerns and lessons are undeniably critical for the prevention and control of future infectious agents. Furthermore, most populaces were introduced to several new public health maintenance strategies, and again, some critical events arose. The purpose of this perspective is to thoroughly analyze all these issues and the concerns, such as the molecular diagnostics’ terminologies, their role, as well as the quantity and quality issues with a molecular diagnostics’ test result. Furthermore, it is speculated that society will be more vulnerable in the future and prone to emerging infectious diseases; thus, a novel preventive medicine’s plan for the prevention and control of future (re)emerging infectious diseases is presented, so as to aid the early prevention of future epidemics and pandemics.

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“…This approach is based on computational techniques that seek potential vaccine candidates using the pathogen proteomic data. The recently reported subunit vaccine of COVID-19 ( 14 ) has been designed using this approach. Such techniques are also being applied to combat HIV and influenza infections ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Experimental trials of predicted CD4+ and CD8+ T-cell epitopes of respiratory syncytial virus

Qousain Naqvi,

Muhammad,

Guo

et al. 2024

Front. Immunol.

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BackgroundRespiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people.MethodsWe focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4+ and CD8+ T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through in-vitro and in-vivo studies involving healthy and diseased animal models. ResultsFor each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of <5. Experimental validation of these peptides on female BALB/c mice was conducted before and after infection with the RSV A2 line 19f. We found that the 3RVMHCI (CD8+) epitope of the F protein showed significant results of white blood cells (19.72 × 103 cells/μl), neutrophils (6.01 × 103 cells/μl), lymphocytes (12.98 × 103 cells/μl), IgG antibodies (36.9 µg/ml), IFN-γ (86.96 ng/L), and granzyme B (691.35 pg/ml) compared to control at the second booster dose of 10 µg. Similarly, 4RVMHCII (CD4+) of the F protein substantially induced white blood cells (27.08 × 103 cells/μl), neutrophils (6.58 × 103 cells/μl), lymphocytes (16.64 × 103 cells/μl), IgG antibodies (46.13 µg/ml), IFN-γ (96.45 ng/L), and granzyme B (675.09 pg/ml). In-vitro studies showed that 4RVMHCII produced a significant level of antibodies in sera on day 45 comparable to mice infected with the virus. 4RVMHCII also induced high IFN-γ and IL-2 secretions on the fourth day of the challenge compared to the preinfectional stage.ConclusionIn conclusion, epitopes of the F protein showed considerable immune response and are suitable for further validation.

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COVID-19 vaccine design using reverse and structural vaccinology, ontology-based literature mining and machine learning

Cited by 11 publications

References 186 publications

Ontological representation, modeling, and analysis of parasite vaccines

Ontological representation, modeling, and analysis of parasite vaccines

The Deceptive COVID-19: Lessons from Common Molecular Diagnostics and a Novel Plan for the Prevention of the Next Pandemic

Experimental trials of predicted CD4+ and CD8+ T-cell epitopes of respiratory syncytial virus

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