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1.
Mol Immunol ; 106: 1-11, 2019 02.
Article in English | MEDLINE | ID: mdl-30572282

ABSTRACT

Peptide vaccines constitute an interesting alternative to classical vaccines due to the possibility of selecting specific epitopes, easy of production and safety. However, an inadequate design may render these peptides poorly immunogenic or lead to undesirable outcomes (e.g., formation of B neoepitopes). As an approach to vaccine development, we evaluated the antibody response to chimeras composed of two or three known B epitopes from Trichinella and Fasciola, and several linkers (GSGSG, GPGPG and KK) in species as different as mice, sheep and turbot. All these species could mount an effective immune response to the short chimeric peptides. Nevertheless, this response depended on several factors including a favorable orientation of B-cell epitopes, adequateness of linkers and/or probability of formation of T neoepitopes. We also observed that, at least in mice, the inclusion of a decoy epitope may have favorable consequences on the antibody response to other epitopes in the chimera.


Subject(s)
Antibodies, Helminth/immunology , Antibody Formation , Antigens, Helminth/immunology , Epitopes, B-Lymphocyte/immunology , Fasciola/immunology , Helminth Proteins/immunology , Peptides/immunology , Trichinella/immunology , Animals , Antigens, Helminth/chemistry , Antigens, Helminth/genetics , Epitopes, B-Lymphocyte/genetics , Fasciola/genetics , Female , Flatfishes , Helminth Proteins/genetics , Mice , Mice, Inbred BALB C , Peptides/pharmacology , Sheep , Species Specificity , Trichinella/genetics
2.
J Neurol ; 260(8): 1951-9, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23086181

ABSTRACT

The etiology of multiple sclerosis has not yet been fully described. A potential link between the recombinant hepatitis B vaccine and an increased risk of onset or exacerbation of multiple sclerosis emerged in the mid-1990s, leading to several spontaneous reports and studies investigating this association. We conducted a critical systematic review aimed at assessing whether hepatitis B vaccination increases the risk of onset or relapse of multiple sclerosis and other central nervous system demyelinating diseases. MEDLINE and EMBASE were used as data sources, and the search covered the period between 1981 and 2011. Twelve references met the inclusion criteria. No significant increased risk of onset or relapse of the diseases considered was associated with hepatitis B vaccination, except in one study. Most studies included in this review displayed methodological limitations and heterogeneity among them, which rendered it impossible to draw robust conclusions about the safety of hepatitis B vaccination in healthy subjects and patients with multiple sclerosis. Therefore, on the basis of current data there is no need to modify the vaccination recommendations; however, there is a need to improve the quality of observational studies with emphasis on certain considerations that are discussed in this review.


Subject(s)
Demyelinating Diseases/etiology , Hepatitis B Vaccines/adverse effects , Vaccines, Synthetic/adverse effects , Humans , Multiple Sclerosis/etiology , Observational Studies as Topic/standards , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/etiology , Risk , Treatment Outcome , Vaccination/adverse effects
3.
Mol Biochem Parasitol ; 179(2): 80-90, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21723885

ABSTRACT

Fascioliasis is a re-emerging parasitosis produced by liver flukes of the genus Fasciola. In this study we used protein fingerprinting (PMF) and MS/MS analysis to investigate the Fasciola secretory antigens that are recognized by mAb MM3. The results showed that mAb MM3 binds to several Fasciola cathepsins L1 and L2, but also co-purifies a Kunitz-type protein previously described in F. hepatica, which appears to bind to Fasciola cathepsins L. After identifying the target antigens for mAb MM3, we cloned and expressed a cathepsin L1 isoform in E. coli (gb|FR848428), which after refolding exhibited the MM3-recognized epitope and displayed cysteine protease activity. Using native, folded-recombinant and denatured-recombinant Fasciola cathepsins L as targets, we demonstrated that during F. hepatica infections in sheep, antibody responses to linear and conformational epitopes present on cathepsins L are promoted. However, the antibody response to linear epitopes was only detected in significant amounts in animals suffering from repeated infections. A different antibody response to linear and conformational epitopes also appears to occur in rabbits immunized with native or recombinant unfolded cathepsins, as sera from animals immunized with the latter did not react with native cathepsins and vice versa. In addition, the ELISA inhibitions showed that the MM3 epitope is not recognized by rabbits, which explains the usefulness of these species for producing capture antibodies for use in MM3-ELISA assays.


Subject(s)
Antibodies, Monoclonal/immunology , Cathepsins/immunology , Fasciola hepatica/immunology , Amino Acid Sequence , Animals , Antibody Formation , Cathepsins/genetics , Cathepsins/metabolism , Cattle/parasitology , Cloning, Molecular , Epitopes/immunology , Escherichia coli/genetics , Escherichia coli/metabolism , Fasciola hepatica/genetics , Fascioliasis/immunology , Fascioliasis/parasitology , Feces/parasitology , Molecular Sequence Data , Protein Refolding , Rabbits/blood , Rabbits/immunology , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Sheep/blood , Sheep/immunology , Sheep/parasitology
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