Applying high throughput and comprehensive immunoinformatics approaches to design a trivalent subunit vaccine for induction of immune response against emerging human coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2.

Coronaviruses (CoVs) cause diseases such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19). Therefore, this study was conducted to combat major CoVs via a trivalent subunit vaccine, which was engineered by implementing sequences of spike (S) protein, nucleocapsid (N), envelope (E), membrane (M) protein, non-structural protein (nsp) 3, and nsp8 antigens. The CTL, HTL, MHC I, and IFN-γ epitopes were predicted via CTLPRED, IEDB, and IFN epitope servers, respectively. Also, to stimulate strong helper T lymphocytes (HTLs) responses, Pan HLA DR-binding epitope (PADRE) was used. Also, for boosting the immune response, ß-defensin 2 was added to the construct as an adjuvant. Furthermore, TAT was applied to the vaccine to facilitate the intracellular delivery. Finally, TAT, adjuvant, PADRE, and selected epitopes were appropriately assembled. Based on the predicted epitopes, a trivalent multi-epitope vaccine with a molecular weight of 74.8 kDa was constructed. Further analyses predicted the molecule to be a strong antigen, and a non-allergenic and soluble protein. Secondary and tertiary structures were predicted. Additionally, analyses validated the stability of the proposed vaccine. Molecular docking and molecular dynamics simulation (MDS) showed binding affinity and stability of the vaccine-TLR3 complex was favorable. The predicted epitopes demonstrated a strong potential to stimulate T and B-cell mediated immune responses. Furthermore, codon optimization and in silico cloning guaranteed increased expression. In summary, investigations demonstrated that this next-generation approach might provide a new horizon for the development of a highly immunogenic vaccine against SARS-CoV, MERS-CoV, and SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Pathophysiological roles of chronic low-grade inflammation mediators in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common hormonal imbalance disease in reproductive-aged women. Its basic characteristics are ovulatory dysfunction and ovarian overproduction of androgens that lead to severe symptoms such as insulin resistance, hirsutism, infertility, and acne. Notwithstanding the disease burden, its underlying mechanisms remain unknown, and no causal therapeutic exists. In recent years, further studies showed that inflammation processes are involved in ovulation and play a key role in ovarian follicular dynamics. Visceral adipose tissue can cause inflammatory response and maintenance of the inflammation state in adipocytes by augmented production of inflammatory cytokines, monocyte chemoattractant proteins, and recruitment of the immune cell. Therefore, the PCOS can be related to a low-grade inflammation state and inflammatory markers. Investigating the inflammatory processes and mediators that contribute to the commencement and development of PCOS can be a critical step for better understanding the pathophysiology of the disease and its treatment through inhibition or control of related pathways. In the present review, we discuss the pathophysiological roles of chronic low-grade inflammation mediators including inflammasome-related cytokines, interleukin-1ß (IL-1ß), and IL-18 in PCOS development.

Development of a conserved chimeric vaccine based on helper T-cell and CTL epitopes for induction of strong immune response against Schistosoma mansoni using immunoinformatics approaches.

Currently, three recombinant antigens based vaccines are under clinical trials against Schistosomiasis, but there is no vaccine available for prophylaxis or therapeutic. This study was conducted to construct a multi-epitope based vaccine against Schistosoma mansoni via utilizing Sm14, Sm21.7, Sm23, Sm29, Smp80, Sm-CB and SM-TSP-2 antigens. Helper T lymphocyte (HTL), cytotoxic T lymphocyte (CTL) and IFN-γ epitopes were predicted. Furthermore, Pan HLA DR-binding epitope was added to the vaccine. Moreover, 50S ribosomal protein L7/L12 of Mycobacterium tuberculosis as a novel TLR4 agonist was applied. The TAT peptide was added to the vaccine to augment intracellular delivery. The selected epitopes were linked together through appropriate linkers and chimeric vaccine was constructed with 617 amino acids with molecular weight of 65.43 kDa. Physico-chemical properties revealed a soluble protein with antigenic and non-allergic properties. Further analyses validated the stability of the construct that was able to interact with TLR4. Immunoinformatics analysis demonstrated the strong potential of constructed vaccine to stimulate T and B-cell mediated immune responses. In summary, obtained data indicated that the proposed vaccine can properly induce both T and B cells immune responses and could possibly be utilized for prophylactic or therapeutic aims in response to infection caused by S. mansoni.

Development a multi-epitope driven subunit vaccine for immune response reinforcement against Serogroup B of Neisseria meningitidis using comprehensive immunoinformatics approaches.

Serogroup B of Neisseria meningitidis is the main cause of mortality due to meningococcal meningitis. Despite of many investigations, there is still no effective vaccine to prevent this serious infection. Therefore, this study was conducted to design a multi-epitope based vaccine through immunoinformatics approaches. The T CD4+ and TCD8+ cells along with IFN-γ inducing epitopes were selected from TspA, FHbp, NspA, TbpB, PilQ and NspA antigens form serogroup B of Neisseria meningitidis. Furthermore, to induce strong helper T lymphocytes (HTLs) responses, Pan HLA DR-binding epitope (PADRE) was used. In addition, loop 5 and 7 of the PorB as a TLR2 agonist were added to the vaccine construct. Physico-chemical properties, secondary and tertiary structures of the proposed construct were assessed. Finally, homology modeling, refinement and molecular docking were carried out to evaluated the construct tertiary structure and protein-protein interaction, respectively. By fusing the CTL, HTL and IFN-γ predicted epitopes along with suitable adjuvant and linkers, a multi-epitope vaccine was constructed with a TAT sequence of HIV at the N-terminal. Immunoinformatics analyses confirmed a soluble and non-allergic protein with a molecular weight of 62.5 kDa and high antigenicity. Furthermore, the stability of the multi-epitope construct was established and showed strong potential to generate humoral and cell-mediated immune responses. In addition, through molecular docking and dynamic simulation, the microscopic interaction between the vaccine construct and TLR-2 were verified. In summary, immunoinformatics analysis demonstrated that the constructed multi-epitope vaccine had a strong potential of T and B-cell stimulation and it could possibly be used for prophylactic or therapeutic aims to protect against serogroup B of N. meningitidis.