Carrier induced epitopic suppression of antibody responses induced by virus-like particles is a dynamic phenomenon caused by carrier-specific antibodies

Abstract

Pre-existing immunity against vaccine carrier proteins has been reported to inhibit the immune response against antigens conjugated to the same carrier by a process termed carrier induced epitopic suppression (CIES). Hence understanding the phenomenon of CIES is of major importance for the development of conjugate vaccines. Virus-like particles (VLPs) are a novel class of potent immunological carriers which have been successfully used to enhance the antibody response to virtually any conjugated antigen. In the present study we investigated the impact of a pre-existing VLP-specific immune response on the development of antibody responses against a conjugated model peptide after primary, secondary and tertiary immunization. Although VLP-specific immune responses led to reduced peptide-specific antibody titers, we showed that CIES against peptide–VLP conjugates could be overcome by high coupling densities, repeated injections and/or higher doses of conjugate vaccine.Furthermore we dissected VLP-specific immunity by adoptively transferring VLP-specific antibodies, B-cells or Thelper cells separately into naïve mice and found that the observed CIES against peptide–VLP conjugates was mainly mediated by carrier-specific antibodies.