Dataset Information

In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine.

ABSTRACT: Human papillomavirus (HPV) is the most common sexually transmitted infection in the world and the main cause of cervical cancer. Nowadays, the virus-like particles (VLPs) based on L1 proteins have been considered as the best candidate for vaccine development against HPV infections. Two commercial HPV (Gardasil and Cervarix) are available. These HPV VLP vaccines induce genotype-limited protection. The major impediments such as economic barriers especially gaps in financing obstructed the optimal delivery of vaccines in developing countries. Thus, many efforts are underway to develop the next generation of vaccines against other types of high-risk HPV. In this study, we developed DNA constructs (based on L1 and L2 genes) that were potentially immunogenic and highly conserved among the high-risk HPV types. The framework of analysis include (1) B-cell epitope mapping, (2) T-cell epitope mapping (i.e., CD4+ and CD8+ T cells), (3) allergenicity assessment, (4) tap transport and proteasomal cleavage, (5) population coverage, (6) global and template-based docking, and (7) data collection, analysis, and design of the L1 and L2 DNA constructs. Our data indicated the 8-epitope candidates for helper T-cell and CTL in L1 and L2 sequences. For the L1 and L2 constructs, combination of these peptides in a single universal vaccine could involve all world population by the rate of 95.55% and 96.33%, respectively. In vitro studies showed high expression rates of multiepitope L1 (~57.86%) and L2 (~68.42%) DNA constructs in HEK-293T cells. Moreover, in vivo studies indicated that the combination of L1 and L2 DNA constructs without any adjuvant or delivery system induced effective immune responses, and protected mice against C3 tumor cells (the percentage of tumor-free mice: ~66.67%). Thus, the designed L1 and L2 DNA constructs would represent promising applications for HPV vaccine development.

SUBMITTER: Namvar A

PROVIDER: S-EPMC6811573 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine.

Namvar Ali A Bolhassani Azam A Javadi Gholamreza G Noormohammadi Zahra Z

Scientific reports 20191023 1

Human papillomavirus (HPV) is the most common sexually transmitted infection in the world and the main cause of cervical cancer. Nowadays, the virus-like particles (VLPs) based on L1 proteins have been considered as the best candidate for vaccine development against HPV infections. Two commercial HPV (Gardasil and Cervarix) are available. These HPV VLP vaccines induce genotype-limited protection. The major impediments such as economic barriers especially gaps in financing obstructed the optimal ...[more]

PMID: 31645650

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Project description:Vaccination with minor capsid protein L2 induces antibodies that cross-neutralize diverse papillomavirus types. However, neutralizing antibody titers against the papillomavirus type from which the L2 vaccine was derived are generally higher than the titers against heterologous types, which could limit effectiveness against heterologous types. We hypothesized that vaccination with concatenated multitype L2 fusion proteins derived from known cross-protective epitopes of several divergent human papillomavirus (HPV) types might enhance immunity across clinically relevant HPV genotypes.Antibody responses of mice (n = 120) and rabbits (n = 23) to vaccination with HPV-16 amino-terminal L2 polypeptides or multitype L2 fusion proteins, namely, 11-200 x 3 (HPV types 6, 16, 18), 11-88 x 5 (HPV types 1, 5, 6, 16, 18), or 17-36 x 22 (five cutaneous, two mucosal low-risk, and 15 oncogenic types), that were formulated alone or in GPI-0100, alum, or 1018 ISS adjuvants were compared with vaccination with L1 virus-like particles (VLPs), including Gardasil, a licensed quadrivalent HPV L1 vaccine, and a negative control. Mice were challenged with HPV-16 pseudovirions 4 months after vaccination. Statistical tests were two-sided.The HPV-16 L2 polypeptides generated robust HPV-16-neutralizing antibody responses, albeit lower than those to HPV-16 L1 VLPs, and lower responses against other HPVs. In contrast, vaccination with the multitype L2 fusion proteins 11-200 x 3 and 11-88 x 5 induced high serum neutralizing antibody titers against all heterologous HPVs tested. 11-200 x 3 formulated in GPI-0100 adjuvant or alum with 1018 ISS protected mice against HPV-16 challenge (reduction in HPV-16 infection vs phosphate-buffered saline control, P < .001) 4 months after vaccination as well as HPV-16 L1 VLPs, but 11-200 x 3 alone or formulated with either alum or 1018 ISS was less effective (reduction in HPV-16 infection, P < .001).Concatenated multitype L2 proteins in adjuvant have potential as pan-oncogenic HPV vaccines.

Project description:Multi-word expressions (MWEs) are fixed, conventional phrases often used by native speakers of a given language (L1). The type of MWEs investigated in this study were collocations. For bilinguals who have intensive contact with the second language (L2), collocational patterns can be transferred from the L2 to the L1 as a result of cross-linguistic influence (CLI). For example, bilingual migrants can accept collocations from their L2 translated to their L1 as correct. In this study, we asked whether such CLI is possible in native speakers living in the L1 environment and whether it depends on their L2 English proficiency. To this end, we created three lists of expressions in Polish: (1) well-formed Polish verb-noun collocations (e.g., ma sens - ∗has sense), (2) collocational calques from English (loan translations), where the English verb was replaced by a Polish translation equivalent (e.g., ∗ robi sens - makes sense), and, as a reference (3) absurd verb-noun expression, where the verb did not collocate with the noun (e.g., ∗ zjada sens - ∗eats sense). We embedded the three types of collocations in sentences and presented them to L1 Polish participants of varying L2 English proficiency in two experiments. We investigated whether L2 calques would (1) be explicitly judged as non-native in the L1; (2) whether they would evoke differential brain response than native L1 Polish equivalents in the event-related potentials (ERPs). We also explored whether the sensitivity to CLI in calques depended on participants' level of proficiency in L2 English. The results indicated that native speakers of Polish assessed the calques from English as less acceptable than the correct Polish collocations. Still, there was no difference in online processing of correct and calques collocations as measured by the ERPs. This suggests a dissociation between explicit offline judgments and indices of online language processing. Interestingly, English L2 proficiency did not modulate these effects. The results indicate that the influence of English on Polish is so pervasive that collocational calques from this language are likely to become accepted and used by Poles.

Dataset Information

In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine.

Publications

In silico/In vivo analysis of high-risk papillomavirus L1 and L2 conserved sequences for development of cross-subtype prophylactic vaccine.

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