***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: ABSTRACT We report the first phase I trial to assess the safety and immunogenicity of a malaria vaccine c and i date , ICC-1132 ( Malarivax ) , composed of a modified hepatitis B virus core protein ( HBc ) containing minimal epitopes of the Plasmodium falciparum circumsporozoite ( CS ) protein . When expressed in Escherichia coli , the recombinant ICC-1132 protein forms virus-like particles that were found to be highly immunogenic in pre clinical studies of mice and monkeys . Twenty healthy adult volunteers received a 20- or a 50-μg dose of alum-adsorbed ICC-1132 administered intramuscularly at 0 , 2 , and 6 months . The majority of volunteers in the group receiving the 50-μg dose developed antibodies to CS repeats as well as to HBc . Malaria-specific T cells that secreted gamma interferon were also detected after a single immunization with ICC-1132-alum . These studies support ICC-1132 as a promising malaria vaccine c and i date for further clinical testing using more-potent adjuvant formulations and confirm the potential of modified HBc virus-like particles as a delivery platform for vaccines against other human pathogens ABSTRACT Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses . In a previous phase I trial , an alum formulation of ICC-1132 , a malaria vaccine c and i date comprising hepatitis B core ( HBc ) virus-like particle containing Plasmodium falciparum circumsporozoite ( CS ) protein epitopes , was shown to elicit Plasmodium falciparum-specific antibody and cellular responses . The present study was design ed as a single-blind , escalating-dose phase I trial to evaluate the safety and immunogenicity of single intramuscular doses of ICC-1132 formulated in the more potent water-in-oil adjuvant Montanide ISA 720 ( ICC-1132/ISA 720 ) . The vaccine was safe and well tolerated , with transient injection site pain as the most frequent complaint . All vaccinees that received either 20 μg or 50 μg of ICC-1132/ISA 720 developed antiimmunogen and anti-HBc antibodies . The majority of volunteers in these two groups developed sporozoite-specific antibodies , predominantly of opsonizing immunoglobulin G subtypes . Peak titers and persistence of parasite-specific antibody following a single injection of the ISA 720 formulated vaccine were comparable to those obtained following two to three immunizations with alum-adsorbed ICC-1132 . Peripheral blood mononuclear cells of ICC-1132/ISA 720 vaccinees proliferated and released cytokines ( interleukin 2 and gamma interferon ) when stimulated with recombinant P. falciparum CS protein , and CS-specific CD4 + T-cell lines were established from volunteers with high levels of antibodies to the repeat region . The promising results obtained with a single dose of ICC-1132 formulated in Montanide ISA 720 encourage further clinical development of this malaria vaccine c and i date This open-labeled phase I study provides the first demonstration of the immunogenicity of a precisely defined synthetic polyoxime malaria vaccine in volunteers of diverse HLA types . The polyoxime , design ated (T1BT*)4-P3C , was constructed by chemoselective ligation , via oxime bonds , of a tetrabranched core with a peptide module containing B cell epitopes and a universal T cell epitope of the Plasmodium falciparum circumsporozoite protein . The triepitope polyoxime malaria vaccine was immunogenic in the absence of any exogenous adjuvant , using instead a core modified with the lipopeptide P3C as an endogenous adjuvant . This totally synthetic vaccine formulation can be characterized by mass spectroscopy , thus enabling the reproducible production of precisely defined vaccines for human use . The majority of the polyoxime-immunized  volunteers ( 7/10 ) developed high levels of anti-repeat Abs that reacted with the native circumsporozoite on P. falciparum sporozoites . In addition , these seven volunteers all developed T cells specific for the universal epitope , termed T * , which was originally defined using CD4 + T cells from protected volunteers immunized with irradiated P. falciparum sporozoites . The excellent correlation of T*-specific cellular responses with high anti-repeat Ab titers suggests that the T * epitope functioned as a universal Th cell epitope , as predicted by previous peptide/HLA binding assays and by immunogenicity studies in mice of diverse H-2 haplotypes . The current phase I trial suggests that polyoximes may prove useful for the development of highly immunogenic , multicomponent synthetic vaccines for malaria , as well as for other pathogens The objectives of this non-r and omized , non-blinded , dose-escalating Phase I clinical trial were to assess the safety , reactogenicity and immunogenicity of ICC-1132 formulated with Alhydrogel ( aluminum hydroxide ) in 51 healthy , malaria-naive adults aged 18 to 45 years .  ICC-1132 ( Malariavax ) is a recombinant , virus-like particle malaria vaccine comprised of hepatitis core antigen engineered to express the central repeat regions from Plasmodium falciparum circumsporozoite protein containing an immunodominant B [ (NANP)3 ] epitope , an HLA-restricted CD4 ( NANPNVDPNANP ) epitope and a universal T cell epitope ( T * ) ( amino acids 326—345 , NF54 isolate ) . We assessed an Alhydrogel ( aluminum hydroxide)-adjuvanted vaccine formulation at three ICC-1132 dose levels , each injected intramuscularly ( 1.0 mL ) on study days 0 , 56 and 168 . A saline vaccine formulation was found to be unstable after prolonged storage and this formulation was subsequently removed from the study . Thirty-two volunteers were followed for one year . Local and systemic adverse clinical events were measured and immune responses to P. falciparum and hepatitis B virus core antigens were determined utilizing the following assays : IgG and IgM ELISA , indirect immunofluorescence against P. falciparum sporozoites , circumsporozoite precipitin ( CSP ) and transgenic sporozoite neutralization assays . Cellular responses were measured by proliferation and IL-2 assays . Local and systemic reactions were similarly mild and well tolerated between dose cohorts . Depending on the ICC-1132 vaccine concentration , 95 to 100 % of volunteers developed antibody responses to the ICC-1132 immunogen and HBc after two injections ; however , only 29—75 % and 29—63 % of volunteers , respectively , developed malaria-specific responses measured by the malaria repeat synthetic peptide ELISA and IFA ; 2 of 8 volunteers had positive reactions in the CSP assay . Maximal transgenic sporozoite neutralization assay inhibition was 54 % . Forty-seven to seventy-five percent demonstrated T cell proliferation in response to ICC-1132 or to recombinant circumsporozoite protein ( rCS ) NF-54 isolate . This c and i date malaria vaccine was well tolerated , but the vaccine formulation was poorly immunogenic . The vaccine may benefit from a more powerful adjuvant to improve immunogenicity . Trial Registration Clinical Trials.gov BACKGROUND Existing anthelmintic drugs ( eg , albendazole and mebendazole ) have low efficacy against the intestinal nematode species Trichuris trichiura and the drug pipeline is exhausted . We aim ed to investigate the strategy of combination chemotherapy with existing drugs to establish whether their efficacy could be enhanced and broadened . METHODS In this r and omised controlled trial , we compared three drug combinations and one st and ard drug alone in children aged 6 - 14 years in two schools on Pemba Isl and , Tanzania infected with T trichiura and concomitant intestinal nematodes . We assigned children , via a r and omisation list with block sizes of either four or eight , to orally receive albendazole ( 400 mg ) plus ivermectin ( 200 μg/kg ) ; albendazole ( 400 mg ) plus mebendazole ( 500 mg ) ; albendazole ( 400 mg ) plus oxantel pamoate ( 20 mg/kg ) ; or mebendazole ( 500 mg ) alone . The primary endpoints were the proportion of children cured of T trichiura infection and the reduction of T trichiura eggs in stool based on geometric means , both analysed by available case . This study is registered with IS RCT N , number IS RCT N80245406 . FINDINGS We r and omly assigned 440 eligible children infected with T trichiura between Sept 2 , and Oct 18 , 2013 , to one of the four treatment groups ( 110 children per group ) . Data for 431 children were included in the analysis for the primary endpoints . Albendazole plus oxantel pamoate ( 74 of 108 children cured [ 68·5 % , 95 % CI 59·6 - 77·4 ] ; egg reduction 99·2 % , 98·7 - 99·6 ) and albendazole plus ivermectin ( 30 of 109 cured [ 27·5 % , 19·0 - 36·0 ] ; egg reduction 94·5 % , 91·7 - 96·3 ) were significantly more effective against T trichiura than mebendazole alone ( nine of 107 cured [ 8·4 % , 3·1 - 13·8 ] ; egg reduction 58·5 % , 45·2 - 70·9 ) . Albendazole plus mebendazole  had similar low efficacy ( nine of 107 cured [ 8·4 % , 3·1 - 13·8 ; egg reduction 51·6 % , 35·0 - 65·3 ) to mebendazole alone . About a fifth of the children reported adverse events , which were mainly mild . Abdominal cramps and headache were the most common adverse events after treatment ; abdominal cramps were reported by 13 ( 12·0 % ) children for albendazole plus ivermectin , 10 ( 9·3 % ) for albendazole plus mebendazole , 20 ( 18·2 % ) for albendazole plus oxantel pamoate , and 16 ( 14·5 % ) for mebendazole ; headaches were reported by 5 ( 4·6 % ) children for albendazole plus ivermectin , 6 ( 5·6 % ) for albendazole plus mebendazole , 12 ( 10·9 % ) for albendazole plus oxantel pamoate , and 7 ( 6·4 % ) for mebendazole . INTERPRETATION Our head-to-head comparison of three combination chemotherapies showed the highest efficacy for albendazole plus oxantel pamoate for the treatment of infection with T trichiura . Further studies should investigate the combination of albendazole plus oxantel pamoate so that it can be considered for soil-transmitted helminthiasis control programmes . FUNDING Medicor Foundation and Swiss National Science Foundation Abstract Allergy is an overreaction by the immune system to a previously encountered , ordinarily harmless substance —typically proteins— result ing in skin rash , swelling of mucous membranes , sneezing or wheezing , or other abnormal conditions . The use of modified proteins is increasingly widespread : their presence in food , commercial products , such as washing powder , and medical therapeutics and diagnostics , makes predicting and identifying potential allergens a crucial societal issue . The prediction of allergens has been explored widely using bioinformatics , with many tools being developed in the last decade ; many of these are freely available online . Here , we report a set of novel models for allergen prediction utilizing amino acid E-descriptors , auto- and cross-covariance transformation , and several machine learning methods for classification , including logistic regression ( LR ) , decision tree ( DT ) , naïve Bayes ( NB ) , r and om forest ( RF ) , multilayer perceptron ( MLP ) and k nearest neighbours ( kNN ) . The best performing method was kNN with 85.3 % accuracy at 5-fold cross-validation . The result ing model has been implemented in a revised version of the AllerTOP server ( http://www.ddg-pharmfac.net/AllerTOP ) . ABSTRACT We report the first phase I trial to assess the safety and immunogenicity of a malaria vaccine c and i date , ICC-1132 ( Malarivax ) , composed of a modified hepatitis B virus core protein ( HBc ) containing minimal epitopes of the Plasmodium falciparum circumsporozoite ( CS ) protein . When expressed in Escherichia coli , the recombinant ICC-1132 protein forms virus-like particles that were found to be highly immunogenic in pre clinical studies 
    Output:
    
A combined VLP vaccine containing four Trichuris MHC-II T-cell epitopes stimulated dendritic cells and macrophages to produce pro-inflammatory and anti-inflammatory cytokines .
The VLPs were internalized and co-localized in the antigen presenting cell lysosomes .
Upon challenge infection , mice vaccinated with the VLPs+T-cell epitopes showed a significantly reduced worm burden , and mounted Trichuris-specific IgM and IgG2c antibody responses .
The protection of mice by VLPs+T-cell epitopes was characterised by the production of mesenteric lymph node (MLN)-derived Th2 cytokines and goblet cell hyperplasia .
Collectively our data establishes that a combination of in silico genome-based CD4 + T cell epitope prediction , combined with VLP delivery , offers a promising pipeline for the development of an effective , safe and affordable helminth vaccine .
Animals vaccinated with a preparation of four different VLP-antigen fusions showed significant reductions in intestinal worm burdens and associated antibody responses consistent with protection .
The results suggest that a pipeline based on in silico prediction of potent MHC-II T cell epitopes , followed by incorporation into VLPs , could be a strategy which enables rapid translation into a vaccine against Trichuris trichiura