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Development of multiepitope subunit protein vaccines against Toxoplasma gondii using an immunoinformatics approach.

ABSTRACT: Approximately one-third of the world's human population is estimated to have been exposed to the parasite Toxoplasma gondii. Its prevalence is reportedly high in Ethiopia (74.80%) and Zimbabwe (68.58%), and is 40.40% in Nigeria. The adverse effect of this parasite includes a serious congenital disease in the developing fetus of pregnant women. After several efforts to eliminate the disease, only one licensed vaccine 'Toxovax' has been used to avoid congenital infections in sheep. The vaccine has been adjudged expensive coupled with adverse effects and short shelf life. The potential of vaccine to likely revert to virulent strain is a major reason why it has not been found suitable for human use, hence the need for a vaccine that will induce T and B memory cells capable of eliciting longtime immunity against the infection. This study presents immunoinformatics approaches to design a T. gondii-oriented multiepitope subunit vaccine with focus on micronemal proteins for the vaccine construct. The designed vaccine was subjected to antigenicity, immunogenicity, allergenicity and physicochemical parameter analyses. A 657-amino acid multiepitope vaccine was designed with the antigenicity probability of 0.803. The vaccine construct was classified as stable, non-allergenic, and highly immunogenic, thereby indicating the safety of the vaccine construct for human use.

SUBMITTER: Onile OS

PROVIDER: S-EPMC7671309 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Development of multiepitope subunit protein vaccines against <i>Toxoplasma gondii</i> using an immunoinformatics approach.

Onile Olugbenga S OS Ojo Glory J GJ Oyeyemi Bolaji Fatai BF Agbowuro Gbenga O GO Fadahunsi Adeyinka I AI

NAR genomics and bioinformatics 20200701 3

Approximately one-third of the world's human population is estimated to have been exposed to the parasite <i>Toxoplasma gondii</i>. Its prevalence is reportedly high in Ethiopia (74.80%) and Zimbabwe (68.58%), and is 40.40% in Nigeria. The adverse effect of this parasite includes a serious congenital disease in the developing fetus of pregnant women. After several efforts to eliminate the disease, only one licensed vaccine 'Toxovax' has been used to avoid congenital infections in sheep. The vacc ...[more]

PMID: 33575600

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Project description:Klebsiella pneumoniae is an opportunistic Gram-negative bacterium that has become a leading causative agent of nosocomial infections, mainly infecting patients with immunosuppressive diseases. Capsular (K) serotypes K1, K2, K47, and K64 are commonly associated with higher virulence (hypervirulent Klebsiella pneumoniae), and more threateningly, isolates belonging to the last two K serotypes are also frequently associated with resistance to carbapenem (hypervirulent carbapenem-resistant Klebsiella pneumoniae). The prevalence of these isolates has posed significant threats to human health, and there are no appropriate therapies available against them. Therefore, in this study, a method combining immunoinformatics and pangenome analysis was applied for contriving a multiepitope subunit vaccine against these four threatening serotypes. To obtain cross-protection, 12 predicted conserved antigens were screened from the core genome of 274 complete Klebsiella pneumoniae genomes (KL1, KL2, KL47, and KL64), from which the epitopes of T and B cells were extracted for vaccine construction. In addition, the immunological properties, the interaction with Toll-like receptors, and the stability in a simulative humoral environment were evaluated by immunoinformatics methods, molecular docking, and molecular dynamics simulation. All of these evaluations indicated the potency of this constructed vaccine to be an effective therapeutic agent. Lastly, the cDNA of the designed vaccine was optimized and ligated to pET-28a(+) for expression vector construction. Overall, our research provides a newly cross-protective control strategy against these troublesome pathogens and paves the way for the development of a safe and effective vaccine. IMPORTANCE Klebsiella pneumoniae is an opportunistic Gram-negative bacterium that has become a leading causative agent of nosocomial infections. Among the numerous capsular serotypes, K1, K2, K47, and K64 are commonly associated with higher virulence (hypervirulent K. pneumoniae). More threateningly, the last two serotypes are frequently associated with resistance to carbapenem (hypervirulent carbapenem-resistant K. pneumoniae). However, there is currently no therapeutic agent or vaccine specifically against these isolates. Therefore, development of a vaccine against these pathogens is very essential. In this study, for the first time, a method combining pangenome analysis, reverse vaccinology, and immunoinformatics was applied for contriving a multiepitope subunit vaccine against K. pneumoniae isolates of K1, K2, K47, and K64. Also, the immunological properties of the constructed vaccine were evaluated and its high potency was revealed. Overall, our research will pave the way for the vaccine development against these four threatening capsular serotypes of K. pneumoniae.

Dataset Information

Development of multiepitope subunit protein vaccines against Toxoplasma gondii using an immunoinformatics approach.

Publications

Development of multiepitope subunit protein vaccines against <i>Toxoplasma gondii</i> using an immunoinformatics approach.

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