The use of maleimidocaproyloxysuccinimide to prepare malarial peptide carrier immunogens immunogenicity of the linking region

Jones, Graham P.; Edmundson, Harry McLemore; Spencer, Lisa A.; Gale, Julie; Saul, Allan

doi:10.1016/0022-1759(89)90224-x

Cited by 26 publications

(7 citation statements)

References 16 publications

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“…Both groups had weak responses against an unrelated peptide–BSA conjugate, indicating that antibody was being generated against the MCS coupling region used to conjugate the peptide to the carrier protein. This has additionally been reported in other studies, which have used MCS as the coupling reagent for the production of peptide conjugates [22].…”

Section: Discussionsupporting

confidence: 72%

Immunization with a Synthetic Peptide Conjugate Derived from the N‐Terminal Sequence of Either the β‐Chain of Haemoglobin or the Immunosuppressive Protein (reOLT 4) Reduces the Litter Size of Pregnant Rats

et al. 1999

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A synthetic peptide conjugate based on the N-terminal sequence of a 10 000 MW immunosuppressive serum protein (reOLT 4) was used to immunize female Lewis rats prior to mating, in order to determine whether blocking this protein had an effect on pregnancy. The N-terminal sequence of (reOLT 4) has close sequence homology to the beta-chain of rat haemoglobin so a peptide conjugate based on the N-terminal sequence of this protein was also used to immunize female Lewis rats. Controls included animals that were not immunized and animals that received the peptide carrier, diphtheria toxoid (DT). No statistical differences were found in gestation time or litter sizes in these groups. Differences were, however, evident between these groups and animals that received DT-(reOLT 4) (group 4) or the DT-beta-chain haemoglobin (group 5). There were no statistical differences in litter size or gestation time for group 4 when compared with group 5. Enzyme-linked immunosorbent assay and dot-blot analysis revealed that rats from both groups also had strong responses against DT, the peptide conjugate they were immunized with and the corresponding full-length protein. In both cases, animals from group 4 and group 5 had weak responses to the peptide that they did not receive, together with lower erythrocyte counts and haematocrits, and elevated heart to body weight ratios. Additionally, antibody purified on a (reOLT 4) immunoaffinity column was capable of binding to rat erythrocytes. A second investigation comparing anaemia prior to fertilization and maintained anaemia over the gestation period revealed that only the latter was capable of decreasing litter size to the same degree as obtained for groups 4 and 5. We conclude that for groups 4 and 5 it is the autoimmune effect of continual anaemia over the gestation period, mediated by autoantibodies, which results in the observed lower litter size.

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Section: Discussionsupporting

confidence: 72%

Immunization with a Synthetic Peptide Conjugate Derived from the N‐Terminal Sequence of Either the β‐Chain of Haemoglobin or the Immunosuppressive Protein (reOLT 4) Reduces the Litter Size of Pregnant Rats

et al. 1999

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“…The sequence of DNNLVSGP is derived from PfEXP-1 (GenBank accession: AF246997). A cysteine at the N-terminus of the peptide was added to facilitate conjugation to maleimide modified proteins [28]. The lyophilized peptide was dissolved in the buffer of PBS-E (1× PBS, 5 mM EDTA, pH 7.2), and the content of free sulfhydryl in the peptide solution (moles of free thiol per mole of peptide) was calibrated by Ellman's reaction [27].…”

Section: Preparation Of Exp153-rflic Conjugatementioning

confidence: 99%

Salmonella flagellin is a potent carrier–adjuvant for peptide conjugate to induce peptide-specific antibody response in mice

Qian

Guo

et al. 2015

Vaccine

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“…Following the synthesis on a solid phase resin, the J8 peptide was acetylated, purified using preparative HPLC and then conjugated to diphtheria toxoid (DT) as a ‘carrier’ molecule. To facilitate the conjugation to the diphtheria toxoid carrier molecule using 6’-maleimido-caproyl n-hydroxy succinimide (MCS) linker [ 34 ], the peptide was synthesized to contain a cysteine (Cys) residue on the C-terminus. Amino acid analysis has shown that the substitution ratio between the peptide and the carrier molecule ranged between 8 to 14 molecules of J8 peptides to 1 molecule of DT and the net w/w was between 310–440 μg of J8 peptide and 560–690μg of DT per mg of J8-DT conjugate.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of safety and immunogenicity of a group A streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial

et al. 2018

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BackgroundGroup A streptococcus (GAS) is a serious human pathogen that affects people of different ages and socio-economic levels. Although vaccination is potentially one of the most effective methods to control GAS infection and its sequelae, few prototype vaccines have been investigated in humans. In this study, we report the safety and immunogenicity of a novel acetylated peptide-protein conjugate vaccine candidate MJ8VAX (J8-DT), when delivered intramuscularly to healthy adults.MethodsA randomized, double-blinded, controlled Phase I clinical trial was conducted in 10 healthy adult participants. Participants were randomized 4:1 to receive the vaccine candidate (N = 8) or placebo (N = 2). A single dose of the vaccine candidate (MJ8VAX), contained 50 μg of peptide conjugate (J8-DT) adsorbed onto aluminium hydroxide and re-suspended in PBS in a total volume of 0.5 mL. Safety of the vaccine candidate was assessed by monitoring local and systemic adverse reactions following intramuscular administration. The immunogenicity of the vaccine was assessed by measuring the levels of peptide (anti-J8) and toxoid carrier (anti-DT)—specific antibodies in serum samples.ResultsNo serious adverse events were reported over 12 months of study. A total of 13 adverse events (AEs) were recorded, two of which were assessed to be associated with the vaccine. Both were mild in severity. No local reactogenicity was recorded in any of the participants. MJ8VAX was shown to be immunogenic, with increase in vaccine-specific antibodies in the participants who received the vaccine. The maximum level of vaccine-specific antibodies was detected at 28 days post immunization. The level of these antibodies decreased with time during follow-up. Participants who received the vaccine also had a corresponding increase in anti-DT serum antibodies.ConclusionsIntramuscular administration of MJ8VAX was demonstrated to be safe and immunogenic. The presence of DT in the vaccine formulation resulted in a boost in the level of anti-DT antibodies.Trial registrationACTRN12613000030774

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The use of maleimidocaproyloxysuccinimide to prepare malarial peptide carrier immunogens immunogenicity of the linking region

Cited by 26 publications

References 16 publications

Immunization with a Synthetic Peptide Conjugate Derived from the N‐Terminal Sequence of Either the β‐Chain of Haemoglobin or the Immunosuppressive Protein (reOLT 4) Reduces the Litter Size of Pregnant Rats

Immunization with a Synthetic Peptide Conjugate Derived from the N‐Terminal Sequence of Either the β‐Chain of Haemoglobin or the Immunosuppressive Protein (reOLT 4) Reduces the Litter Size of Pregnant Rats

Salmonella flagellin is a potent carrier–adjuvant for peptide conjugate to induce peptide-specific antibody response in mice

Evaluation of safety and immunogenicity of a group A streptococcus vaccine candidate (MJ8VAX) in a randomized clinical trial

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