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

Natalia Savelyeva, Catherine A. King, Ellen S. Vitetta, Freda K. Stevenson

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

DNA vaccination can elicit the production of anti-tumor antibodies, thus obviating the need to continuously administer passive anti-body. 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 FcγRIIB 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.

Original languageEnglish (US)
Pages (from-to)10987-10992
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number31
DOIs
StatePublished - Aug 2 2005

Keywords

  • Antibody
  • DNA vaccination
  • Idiotype

ASJC Scopus subject areas

  • General

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