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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 T(helper) cells separately into naïve mice and found that the observed CIES against peptide-VLP conjugates was mainly mediated by carrier-specific antibodies.

Original publication

DOI

10.1016/j.vaccine.2010.02.103

Type

Journal article

Journal

Vaccine

Publication Date

26/07/2010

Volume

28

Pages

5503 - 5512

Keywords

Allolevivirus, Animals, Antibodies, Viral, Antibody Formation, Antigens, B-Lymphocytes, Capsid, Capsid Proteins, Epitopes, Immune Tolerance, Mice, Mice, Inbred BALB C, Mice, Knockout, Peptides, T-Lymphocytes, Helper-Inducer, Virosomes