Immunisation with Phage Displaying Peptides Representing Single Epitopes of the Glycoprotein G Can Give Rise to Partial Protective Immunity to HSV-2

Abstract

Filamentous phage displaying peptides representing single epitopes of the glycoprotein G of HSV-2 (gG2) were used as immunogens via the subcutaneous route in Balb/c mice without additional adjuvant. The phage were isolated from a random phage peptide display library and contain 15-mer peptide inserts that mimic epitopes of gG2. In each case, an antibody response to gG2 was generated that was dependent on the dose of phage administered and on the presence of the peptide insert. Phage displaying epitopes of gG2, which map to amino acids 551-570, were the most immunogenic; interestingly, this region of gG2 is frequently recognised by patients infected with HSV-2. The data also provide interesting information as regards choice of peptide mimics for use as immunogens because, surprisingly, the most antigenic of the individual clones was the least immunogenic. In two of the experiments, mice immunised with phage displaying a single epitope of gG2 were protected against challenge with a lethal dose of whole HSV-2. This suggests a possible role for phage-displayed peptides in inducing protective immunity against pathogens and provides a model system for investigating the underlying mechanisms.

Glycoprotein G of Herpes Simplex Virus 2 as a Novel Vaccine Antigen for Immunity to Genital and Neurological Disease

“…However, clones from a random phage peptide display library obtained by using an anti-mgG-2 MAb (34) were used as immunogens and administered subcutaneously in a vaccination model in mice. The selected phage clones, which contained short stretches of mgG-2 (3 to 4 amino acids), induced partial protection (Յ60%) against challenge with HSV-2 (21).…”

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

“…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).…”

“…Prolongation of survival was slightly longer when a 5-fold greater amount of conjugate was administered, but this was only associated with a modestly higher titer of IgG to GXM. A minimum Ab concentration and affinity was needed for mimotope-induced protection against viral pathogens (52,54). We found that the concentration of IgG to GXM with binding characteristics similar to a high-affinity mouse mAb that is in use in a clinical trial in humans was comparable to that which conferred passive protection against C. neoformans in mice (8).…”

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

“…Unlike complex carrier proteins that contain many BCEs, the Ab response against phage is restricted to the twelve N-terminal residues of pVIII [23] and the outer domains of pIII. Phage have also been shown to elicit CD4 T-cell help, form immunological memory [24] and are well-documented as immunogenic carriers for recombinant peptides [25][26][27][28][29][30][31][32][33][34][35] (for reviews see [36][37][38]). Furthermore, phage can be engineered to enhance the immune response, for example, by the addition of foreign CD4 T-cell epitopes to pIII or pVIII [39,40].…”