Bioinformatics analysis of putative causes for сross-reactive antibodies interacting with antigens derived from various pathogenic human papillomaviruses

Abstract

Human papillomaviruses (HPVs) belong to highly abundant resulting in sexually transmitted virus infections, and cause cervical cancer holding place 4 among most common cancer types in women. In 2012, there were registered 266,000 death cases and 528,000 new cases. At present, three HPV prophylactic vaccines were generated worldwide: bivalent Cervarix, quadrivalent Gardasil and nonavalent Gardasil-9. Examining such vaccines uncovered that they are able to induce anti-HPV antibody production against viral antigens lacked in vaccine formula. The mechanism of such crossneutralizing antibodies recognizing antigens derived from various HPV pathogenic types remains unknown. In our study we attempted to uncover putative basis underlying cross-reactive interaction between vaccine-induced antibodies and non-vaccine antigens by bioinformatical approaches, that might allow optimize generation of future candidate vaccines and obtain more effective polyvalent immunobiological preparations against HPV. We used amino acid sequences of L1 coat protein of four top high-risk oncogenic HPV types (16, 18, 31 and 45) in the study. Work sequences were retrieved from the International Data Base of NCBI (National Center for Biotechnology Information) and aligned by using Clustal Omega’ and BioEdit software. A search and analysis of distinct antigenic determinant (epitopes) were performed by using software suite BepiPred-2.0: Sequential B-Cell Epitope Predictor, DiscoTope 2.0 Server, and SYFPEITHI. Bioinformatics data revealed pronounced potential of cross-neutralizing vaccine-induced antibodies and non-vaccines antigens derived from high-risk pathogenic types HPV 16, 18, 31 and 45 owing to the similarity in antigenic determinants (epitopes). Common linear determinants for T- and B-cells were found in all four types of L1 protein counterparts. In addition, similar three-dimensional B-cell determinants were discovered in HPV16 L1 and HPV18 L1. Antigenic determinants derived from HPV16 L1 and HPV31 L1 exhibited most close similarity. Hence, while immunizing with HPV16 L1, a more pronounced and moderate cross-reactive antibodies interacting with HPV31 L1 as well as HPV18 L1 and HPV45 L1 antigens, respectively, should be expected. Inversely, immunization with HPV18 L1might elicit active and less efficient crossneutralizing response with HPV45 L1 as well as HPV16 L1 and HPV31 L1, respectively.