The Influence of Branched Polypeptide Carriers on the Immunogenicity of Predicted Epitopes of HSV‐1 Glycoprotein D

Abstract

To investigate the role of synthetic polypeptide carriers in inducing an epitope-specific immune response relevant for vaccine design, peptides comprising two distinct regions of herpes simplex virus type I glycoprotein D (1-23 and 273-284) have been conjugated to the branched polypeptides with polylysine backbone, poly[L-Lys-(DL-Alam)] (AK), or poly[L-Lys-(Leui-DL-Alam)] (LAK) and to keyhole limpet haemocyanin (KLH). The magnitude, fine specificity and isotype distribution of the conjugate-, peptide-and carrier-specific antibody responses were characterized in immunized BALB/c and CBA mice. Conjugates containing the polypeptide carrier AK were the most effective in inducing HSV gD-peptide-specific antibody responses while KLH peptide conjugates resulted in conjugate-specific antibody responses without measurable peptide specificity. The efficacy of AK-peptide conjugates was verified by the dominant appearance of peptide-specific antibodies belonging to functionally efficient IgG isotopes, accompanied by low levels of carrier specific antibody responses. Preimmunization of BALB/or CBA mice with AK conjugates comprising the 1-23 or 276-284 HSV peptides resulted in prolonged survival of animals infected with a lethal dose of infectious HSV-1. The potency of these conjugates in eliciting a protective immune response shows a close correlation with the relative levels of conjugate-induced virus-specific antibodies and the neutralizing activity of sera as measured in preimmunized survivors.

Identification of Novel Immunodominant CD4+Th1-Type T-Cell Peptide Epitopes from Herpes Simplex Virus Glycoprotein D That Confer Protective Immunity

“…To investigate whether the Th1-or Th2-type immune responses are more important for protection from HSV-1 infection, mice were immunized with either CD4 ϩ Th1 peptide epitopes (gD , gD 146-179 , gD , and gD 332-358 ) or CD4 ϩ Th2 peptide epitopes (gD , gD 77-104, gD , and gD 287-317 ) ( Table 3). The previously described protective epitope gD (38) was excluded from these experiments. Groups of 10 H-2 d mice were immunized twice with the following: a pool of gD , gD 146-179 , gD , and gD 332-358 emulsified in M-ISA-720 adjuvant or a pool of gD , gD nized control H-2 d mice survived the HSV-1 challenge (Table 3).…”

A novel dominant B-cell epitope of FSHR identified by molecular docking induced specific immune response and suppressed fertility

“…As results demonstrated that no band was seen (lane [11][12][13][14]. It may suggest that peptides quenched the antisera, thus preventing them from binding to FSHR protein.…”

“…It was well known that the peptide used alone could not induce a high titre of antibody because of its poor immunogenicity although it was safe. Although combined with proper carrier protein, most of the immunogenic of the vaccine is against the carrier protein [14]. To overcome this disadvantage, we employed a protein prime-peptide boost strategy to explore the immune responses and fertility inhibition effects in adult male mice.…”

Antibody to HSV gD peptide induced by vaccination does not protect against HSV-2 infection in HSV-2 seronegative women

“…Specifically, this region contains defined CD4+ T-cell epitopes in mice [33, 34] (of note, one of these can protect against lethal HSV-1 challenge [35]) and humans [36, 37] and multiple B-cell epitopes recognized by mouse monoclonal antibodies against gD [31, 32, 38]. Moreover, the gD peptide is also a target of human HSV-neutralizing antibodies [39].…”