Selection of an immunogenic peptide mimic of the capsular polysaccharide of Neisseria meningitidis serogroup A using a peptide display library

A Cryptococcal Capsular Polysaccharide Mimotope Prolongs the Survival of Mice withCryptococcus neoformansInfection

“…Notwithstanding, the conjugates appeared to prime for an amnestic response based on the observation that the IgG titer to GXM increased after C. neoformans infection (upon exposure to either soluble GXM or the capsular polysaccharide of encapsulated C. neoformans), without a concomitant increase in IgG to P13 or IgM to GXM. A peptide-mimotope-induced amnestic response to group A Neisseria meningitidis has also been reported (27). The following evidence suggests that the P13 conjugates elicited a T-dependent response: 1) the P13 conjugate elicited a memory response, 2) IgG1 was the predominant IgG subclass to GXM, and 2) an Ab response to GXM was induced in CBA/n mice, a strain that is unable to mount Ab responses to T-independent Ags (44,47).…”

“…Recently, there has been increased interest in the use of the random peptide phage display technology to identify peptide mimics of unknown carbohydrate Ags as potential vaccine candidates (24,25,27,(37)(38)(39)(40)(41)(42). In light of the fact that the cryptococcal capsular polysaccharide GXM is poorly immunogenic (43) and defined GXM oligosaccharides are not available, the rationale for the peptide-based approach to vaccine design for C. neoformans was 2-fold: 1) peptide surrogates of polysaccharide Ags selected by defined Abs may direct the response to the production of protective Abs and 2) a peptide-based vaccine should replace the T-independent response to capsular polysaccharide that does not stimulate T cell help (13), with a T-dependent response that induces an amnestic response (40).…”

“…It has also been reported that peptide mimics of a measles virus glycoprotein and group B N. meningitidis did not induce an antimeasles (49) or antimeningococcal response (42), respectively. However, peptide mimics of serotype A meningococcal capsular polysaccharide (27), the Shigella flexneri serotype 5a LPS (41), Lewis Y carbohydrate Ags (50, 51), group B streptococcal capsular polysaccharide (28), a herpes simplex virus glycoprotein (52), and a respiratory syncytical virus-associated glycoprotein (53) have been found to elicit anticarbohydrate responses. Notably, several peptide mimics that were subsequently found to be mimotopes reacted with immune or hyperimmune serum (often from another species than the selecting mAb) to the relevant capsular polysaccharide (27, 28, 54), and we had previously shown in two different studies that P13 inhibited the GXM binding of serum Abs from normal, but not HIV-infected, individuals (11,30).…”

Filamentous phage as an immunogenic carrier to elicit focused antibody responses against a synthetic peptide

“…Synthetic peptides have been used in developing immunogens that target the humoral immune response; typically, to elicit antibodies (Abs) that cross-react with a discrete epitope on a protein (and sometimes on carbohydrate (CHO) [1][2][3][4][5][6] or DNA [7][8][9]). Currently, there are no FDAapproved conjugate vaccines like this; however, there is noteworthy research focused on developing peptides as immunogenic B-cell epitopes (BCEs).…”

“…For example, peptides are being used to produce Abs against specific epitopes on tumor Agns that decrease cell proliferation [10][11][12][13]. Peptides are also used as alternatives to CHO Agns because they can elicit a T-cell dependent immune response along with CHO-cross-reactive Abs [1][2][3][4][5][6]. Others have proposed using peptide immunogens to produce HIV-1 neutralizing Abs [14][15][16].…”