In silico studies of Coxiella burnetii outer membrane proteins (OMPs) as basis to Q fever diagnosis development

Coxiella burnetii is a global, highly infectious intracellular bacterium, able to infect a wide range of hosts and to persist for months in the environment. It is the etiological agent of Q fever—a zoonosis of global priority. Currently, there are no national surveillance data on C. burnetii’s seroprevalence for any South American country, reinforcing the necessity of developing novel and inexpensive serological tools to monitor the prevalence of infections among humans and animals—especially cattle, goats, and sheep. In this study, we used immunoinformatics and computational biology tools to predict specific linear B-cell epitopes in three C. burnetii outer membrane proteins: OMP-H (CBU_0612), Com-1 (CBU_1910), and OMP-P1 (CBU_0311). Furthermore, predicted epitopes were tested by ELISA, as synthetic peptides, against samples of patients reactive to C. burnetii in indirect immunofluorescence assay, in order to evaluate their natural immunogenicity. In this way, two linear B-cell epitopes were identified in each studied protein (OMP-H(51–59), OMP-H(91–106), Com-1(57–76), Com-1(191–206), OMP-P1(197–209), and OMP-P1(215–227)); all of them were confirmed as naturally immunogenic by the presence of specific antibodies in 77% of studied patients against at least one of the identified epitopes. Remarkably, a higher frequency of endocarditis cases was observed among patients who presented an intense humoral response to OMP-H and Com-1 epitopes. These data confirm that immunoinformatics applied to the identification of specific B-cell epitopes can be an effective strategy to improve and accelerate the development of surveillance tools against neglected diseases.

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Computational identification of significant immunogenic epitopes of the putative outer membrane proteins from Mycobacterium tuberculosis

Journal of Genetic Engineering and Biotechnology ◽

10.1186/s43141-021-00148-9 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Shobana Sundar ◽

Lokesh Thangamani ◽

Shanmughavel Piramanayagam

Keyword(s):

Membrane Proteins ◽

B Cell ◽

Outer Membrane ◽

In Silico ◽

Outer Membrane Proteins ◽

Cell Binding ◽

Immunogenic Peptides ◽

Antigenic Properties ◽

Mhc Alleles ◽

Immunodominant Epitopes

AbstractNovel vaccines are required to effectively combat the epidemic spread of tuberculosis. Using in silico approaches, this study focuses on prediction of potential B cell and T cell binding immunogenic epitopes for 30 putative outer membrane proteins of Mtb. Among these, certain immunodominant epitopes of Rv0172, Rv0295c, Rv1006, Rv2264c, and Rv2525c were found, which are capable of binding B-cell and a maximum number of MHC alleles. The selected immunodominant epitopes were screened for their allergenic and antigenic properties, their percentage identity against the human proteome and their structural properties. Further, the binding efficacy of the immunodominant epitopes of Rv0295c and Rv1006 with HLA-DRB1*04:01 was analyzed using molecular docking and molecular dynamics studies. Hence, the in silico-derived immunogenic peptides (epitopes) could potentially be used for the design of subunit vaccines against tuberculosis.

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