Browsing by Author "Surender Mohan"

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Homology modelling and molecular simulation approach to prediction of B-cell and T-cell epitopes in an OMP25 peptide vaccine against Brucella abortus
(Taylor and Francis Ltd., 2023) Dhananjay Jade; Sonal Gupta; Surender Mohan; Sreenivasan Ponnambalam; Michael Harrison; Rakesh Bhatnagar
The live attenuated vaccine composition against brucellosis poses potential risks to recipient animals. Therefore, we have analysed an in-silico approach to design a novel multi-epitope vaccine peptide to elicit a desirable immune response against Brucella abortus infection. This study designed a peptide vaccine based on outer membrane protein from B. abortus. The selected OMP sequence shows 0.7575 antigenic proteins. We predicted the T-cell epitopes of different lengths. Cluster analysis was performed for 180 epitope peptides, showcasing a total of 19 clusters, constituting 14 clusters as Consensus clusters and 5 as Singleton clusters. We select the top three clusters which has 24 peptides showing antigen property. Selected 24-antigen peptides were docked with MHC classes I and II and selected the top eight peptides based on binding energy used for molecular dynamic simulation. Immuno-informatics analysis, Molecular Docking and Molecular simulation indicated that epitope peptide vaccine could work as effective peptides helpful in scheming peptide vaccine against B. abortus infection by developing broad-spectrum peptide vaccine in near future. The use of Omp25 as a vaccine candidate has been supported based on previous experimental studies. Multitope vaccine can be developed which can protect mice against virulent B. abortus challenge. © 2023 Informa UK Limited, trading as Taylor & Francis Group.
Preclinical evidence of nanomedicine formulation to target mycobacterium tuberculosis at its bone marrow niche
(MDPI AG, 2020) Jaishree Garhyan; Surender Mohan; Vinoth Rajendran; Rakesh Bhatnagar
One-third of the world’s population is estimated to be latently infected with Mycobacterium tuberculosis (Mtb). Recently, we found that dormant Mtb hides in bone marrow mesenchymal stem cells (BM-MSCs) post-chemotherapy in mice model and in clinical subjects. It is known that residual Mtb post-chemotherapy may be responsible for increased relapse rates. However, strategies for Mtb clearance post-chemotherapy are lacking. In this study, we engineered and formulated novel bone-homing PEGylated liposome nanoparticles (BTL-NPs) which actively targeted the bone microenvironment leading to Mtb clearance. Targeting of BM-resident Mtb was carried out through bone-homing liposomes tagged with alendronate (Ald). BTL characterization using TEM and DLS showed that the size of bone-homing isoniazid (INH) and rifampicin (RIF) BTLs were 100 ± 16.3 nm and 84 ± 18.4 nm, respectively, with the encapsulation efficiency of 69.5% ± 4.2% and 70.6% ± 4.7%. Further characterization of BTLs, displayed by sustained in vitro release patterns, increased in vivo tissue uptake and enhanced internalization of BTLs in RAW cells and CD271+BM-MSCs. The efficacy of isoniazid (INH)- and rifampicin (RIF)-loaded BTLs were shown using a mice model where the relapse rate of the tuberculosis was decreased significantly in targeted versus non-targeted groups. Our findings suggest that BTLs may play an important role in developing a clinical strategy for the clearance of dormant Mtb post-chemotherapy in BM cells. View Full-Text. © 2020 by the authors.
Simultaneous immunization with omp25 and l7/l12 provides protection against brucellosis in mice
(MDPI AG, 2020) Sonal Gupta; Surender Mohan; Vikas Kumar Somani; Somya Aggarwal; Rakesh Bhatnagar
Currently used Brucella vaccines, Brucella abortus strain 19 and RB51, comprises of live attenuated Brucella strains and prevent infection in animals. However, these vaccines pose potential risks to recipient animals such as attenuation reversal and virulence in susceptible hosts on administration. In this context, recombinant subunit vaccines emerge as a safe and competent alternative in combating the disease. In this study, we formulated a divalent recombinant vaccine consisting of Omp25 and L7/L12 of B. abortus and evaluated vaccine potential individually as well as in combination. Sera obtained from divalent vaccine (Omp25+L7/L12) immunized mice group exhibited enhanced IgG titers against both components and indicated specificity upon immunoblotting reiterating its authenticity. Further, the IgG1/IgG2a ratio obtained against each antigen predicted a predominant Th2 immune response in the Omp25+L7/L12 immunized mice group. Upon infection with virulent B. abortus 544, Omp25+L7/L12 infected mice exhibited superior Log10 protection compared to individual vaccines. Consequently, this study recommends that simultaneous immunization of Omp25 and L7/L12 as a divalent vaccine complements and triggers a Th2 mediated immune response in mice competent of providing protection against brucellosis. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.