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Inhibition of a vaccine-induced anti-tumor B cell response by soluble protein antigen in the absence of continuing T cell help

Inhibition of a vaccine-induced anti-tumor B cell response by soluble protein antigen in the absence of continuing T cell help
Inhibition of a vaccine-induced anti-tumor B cell response by soluble protein antigen in the absence of continuing T cell help
DNA vaccination can elicit the production of anti-tumor antibodies, thus obviating the need to continuously administer passive antibody. This vaccination strategy is particularly important where antibodies have proven to be effective anti-tumor agents. To amplify antibody responses against weak tumor antigens, we previously designed DNA-fusion vaccines incorporating tumor sequences linked to microbial genes. By using a safe idiotypic (Id) antigen from a B cell tumor fused to a fragment C (FrC) sequence from tetanus toxin, we induced both anti-Id and anti-FrC antibodies. It was important to determine whether the antigen itself, either injected or released from residual tumor cells, would boost the antibody response. Id protein not only failed to boost the response, but permanently and rapidly inhibited it by ablating Id-specific memory B cells. In contrast, an Id protein-FrC conjugate boosted both Id-specific and FrC-specific responses. Strikingly, the depletion of CD4+ T cells converted the Id protein-FrC conjugate vaccine into an inhibitor. These findings support the hypothesis that the activation of memory B cells by a DNA vaccine encoding a protein antigen, in the presence of the protein itself, depends completely on T cell help. Furthermore, by using knockout mice, we have shown that inhibition of the Id-specific memory B cells by the Id protein is largely independent of the Fc{gamma}RIIB and, hence, independent of immune complexes. The principles revealed by using a DNA vaccine have implications for all cancer vaccines designed to induce and maintain antibody responses against weak autologous tumor antigens.
antibody, dna vaccination, idiotype
0027-8424
10987-10992
Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7
King, Catherine A.
8239cea6-bbe4-4031-bf3e-8deb5a3dab7f
Vitetta, Ellen S.
af8d0814-e2da-4b80-b80a-b96ffde6ef20
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7
King, Catherine A.
8239cea6-bbe4-4031-bf3e-8deb5a3dab7f
Vitetta, Ellen S.
af8d0814-e2da-4b80-b80a-b96ffde6ef20
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c

Savelyeva, Natalia, King, Catherine A., Vitetta, Ellen S. and Stevenson, Freda K. (2005) Inhibition of a vaccine-induced anti-tumor B cell response by soluble protein antigen in the absence of continuing T cell help. Proceedings of the National Academy of Sciences of the United States of America, 102 (31), 10987-10992. (doi:10.1073/pnas.0505108102).

Record type: Article

Abstract

DNA vaccination can elicit the production of anti-tumor antibodies, thus obviating the need to continuously administer passive antibody. This vaccination strategy is particularly important where antibodies have proven to be effective anti-tumor agents. To amplify antibody responses against weak tumor antigens, we previously designed DNA-fusion vaccines incorporating tumor sequences linked to microbial genes. By using a safe idiotypic (Id) antigen from a B cell tumor fused to a fragment C (FrC) sequence from tetanus toxin, we induced both anti-Id and anti-FrC antibodies. It was important to determine whether the antigen itself, either injected or released from residual tumor cells, would boost the antibody response. Id protein not only failed to boost the response, but permanently and rapidly inhibited it by ablating Id-specific memory B cells. In contrast, an Id protein-FrC conjugate boosted both Id-specific and FrC-specific responses. Strikingly, the depletion of CD4+ T cells converted the Id protein-FrC conjugate vaccine into an inhibitor. These findings support the hypothesis that the activation of memory B cells by a DNA vaccine encoding a protein antigen, in the presence of the protein itself, depends completely on T cell help. Furthermore, by using knockout mice, we have shown that inhibition of the Id-specific memory B cells by the Id protein is largely independent of the Fc{gamma}RIIB and, hence, independent of immune complexes. The principles revealed by using a DNA vaccine have implications for all cancer vaccines designed to induce and maintain antibody responses against weak autologous tumor antigens.

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More information

Published date: 2005
Keywords: antibody, dna vaccination, idiotype
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 26595
URI: http://eprints.soton.ac.uk/id/eprint/26595
ISSN: 0027-8424
PURE UUID: a3ac5d1d-9ccb-4136-97d7-8a9145e74ec8
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 20 Apr 2006
Last modified: 16 Mar 2024 02:54

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Contributors

Author: Catherine A. King
Author: Ellen S. Vitetta

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