Abstract
Recent studies indicate that DNA immunization is powerful in eliciting antigen-specific antibody responses in both animal and human studies. However, there is limited information on the mechanism of this effect. In particular, it is not known whether DNA immunization can also enhance the development of antigen-specific B cell development. In this report, a pilot study was conducted using plague LcrV immunogen as a model system to determine whether DNA immunization is able to enhance LcrV-specific B cell development in mice. Plague is an acute and often fatal infectious disease caused by Yersinia pestis (Y. pestis). Humoral immune responses provide critical protective immunity against plague. Previously, we demonstrated that a DNA vaccine expressing LcrV antigen can protect mice from lethal mucosal challenge. In the current study, we further evaluated whether the use of a DNA priming immunization is able to enhance the immunogenicity of a recombinant LcrV protein vaccine, and in particular, the development of LcrV-specific B cells. Our data indicate that DNA immunization was able to elicit high-level LcrV antibody responses when used alone or as part of a prime-boost immunization approach. Most significantly, DNA immunization was also able to increase the levels of LcrV-specific B cell development. The finding that DNA immunization can enhance antigen-specific B cell responses is highly significant and will help guide similar studies in other model antigen systems.
Highlights
DNA immunization was discovered about 20 years ago
The wild type lcrV gene was PCR-amplified from the LcrV DNA vaccine, as previously described [5] and cloned into the E. coli expression vector, pBAD/gIII (Invitrogen), with a His(6)-Tag at the C-terminus fused with V-antigen
Prime-Boost Group—received LcrV DNA vaccine at Week 0 and the recombinant LcrV protein formulated with adjuvant Incomplete Freund Adjuvant (IFA) at Week 4 by i.m. immunization; (3) Protein Alone Group—received
Summary
DNA immunization was discovered about 20 years ago. While it was initially considered a novel approach to elicit T cell responses, data accumulated in the last decade has further indicated that DNA immunization is very effective in eliciting antibody responses against both viral and bacterial antigens [1,2,3,4,5,6,7], when included as part of a prime-boost immunization [8]. Y. pestis type-III secretion system) have been established as lead antigens for subunit-based plague vaccines and were shown to induce protection against bubonic and pneumonic plague in several animal models [5,7,14,15,16,17,18,19]. These antigens elicited antibodies when administered in humans, the antibody response levels were moderate [20]. We tested whether the heterologous DNA prime-protein boost approach is more effective than the homologous DNA alone or protein alone immunization approaches in eliciting LcrV antigen-specific B cell immune responses
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