Immunity and protection against influenza virus by synthetic peptide corresponding to antigenic sites of hemagglutinin.

Abstract

Four peptides have been synthesized, corresponding to different regions of the H3 influenza hemagglutinin, that are related to antigenic sites "A" and "B" of the molecule. The peptides consisted of the following sequences: 139-146, which forms the "loop" in the native hemagglutinin molecule, with either glycine or aspartic acid at position 144; 147-164, which contains part of antigenic determinant "B"; and 138-164, which comprises both the loop and the area 147-164.The peptides were conjugated to tetanus toxoid and used for immunization of rabbits and mice. All four conjugates elicited an immune response against the homologous peptides, but only the peptides 138-164 and 147-164 gave rise to antibodies that recognized and bound to the intact virus. Protection of mice against challenge infection with A/Eng/42/72 virus was achieved only by immunization with the conjugate (138-164)-TT, which led to partial protective effect. These data emphasize the role of molecular structure in determining the antigenic properties of synthetic peptides and indicate that the length of the peptide could be crucial for enforcing the right folding required to mimic the native structure.

Efficient generation of antibodies to oncoproteins by using synthetic peptide antigens.

“…Van Eldik et al (24) generated antibodies that reacted with calmodulin by utilizing a decapentapeptide but failed to do so with a heptapeptide. Two octapeptides failed to generate antibodies against influenza hemagglutinin, whereas two peptides with 18 or 27 amino acids were effective (25). The observations of Niman et al (7) are also pertinent.…”

Neutralizing activity of anti-peptide antibodies against the principal neutralization domain of human immunodeficiency virus type 1

“…Antibody titres were measured in an indirect ELISA using microtitre plates coated with an excess of peptide RIQRGPGRAFV-TIGK (1 p.g/well) as described (Shapira et at., 1984;Suter, 1982). The midpoint titre is defined as the reciprocal of the serum dilution giving 50% of the maximum absorbance value.…”

Immunogenically Fit Subunit Vaccine Components Via Epitope Discovery from Natural Peptide Libraries

“…Their relatively large size (27-97 amino acids for the three most immunogenically fit NAPs) provides ample opportunities for reproducing multiple conformation-stabilizing interactions present in the intact native pathogen (9,12). In addition, these self-folding native-like domains may be large enough to encompass more than one epitope (33).…”

“…Peptides with excellent antigenicity and immunogenicity frequently lack adequate immunogenic fitness and therefore fail as potential vaccine components (7)(8)(9)(10)(11)(12)(13)(14)(15). A common explanation for this poor immunogenic fitness is the conformational flexibility of most short peptides.…”