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Pilot Study on the Use of DNA Priming Immunization to Enhance Y. pestis LcrV-Specific B Cell Responses Elicited by a Recombinant LcrV Protein Vaccine.

Li W, Wang S, Lu S - Vaccines (Basel) (2013)

Bottom Line: However, there is limited information on the mechanism of this effect.Previously, we demonstrated that a DNA vaccine expressing LcrV antigen can protect mice from lethal mucosal challenge.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. wei.li@umassmed.edu.

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.

No MeSH data available.


Related in: MedlinePlus

V-specific IgG responses induced by various V vaccine regimens in mice: codon optimized V DNA vaccine alone (V-DNA), V DNA vaccine prime followed by V protein boost formulated with IFA (V-DNA + Prot/IFA), V protein formulated with IFA (V-Prot/IFA), V protein alone (V-Prot), or empty DNA vaccine vector alone (Vector). Panels A and B: V-specific antibody titers were measured by ELISA against V protein in mouse sera collected at 2 weeks after the prime (1st immunization) (Panel A) or at 2 weeks after the boost (2nd immunization) (Panel B). Panel C: V-specific IgG concentrations at 2 weeks after the boost (2nd) immunization. Each bar represents the mean V-specific IgG titers or concentrations in each group of 5 mice with standard error. Statistically significant differences (p < 0.05) are indicated as “*”, “#” or “^” when comparing V-DNA, V-DNA + Prot/IFA, and V-Prot/IFA groups.
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vaccines-02-00036-f003: V-specific IgG responses induced by various V vaccine regimens in mice: codon optimized V DNA vaccine alone (V-DNA), V DNA vaccine prime followed by V protein boost formulated with IFA (V-DNA + Prot/IFA), V protein formulated with IFA (V-Prot/IFA), V protein alone (V-Prot), or empty DNA vaccine vector alone (Vector). Panels A and B: V-specific antibody titers were measured by ELISA against V protein in mouse sera collected at 2 weeks after the prime (1st immunization) (Panel A) or at 2 weeks after the boost (2nd immunization) (Panel B). Panel C: V-specific IgG concentrations at 2 weeks after the boost (2nd) immunization. Each bar represents the mean V-specific IgG titers or concentrations in each group of 5 mice with standard error. Statistically significant differences (p < 0.05) are indicated as “*”, “#” or “^” when comparing V-DNA, V-DNA + Prot/IFA, and V-Prot/IFA groups.

Mentions: The temporal pattern of antibody responses was measured using a fixed serum dilution; therefore, additional ELISA studies were conducted to measure actual antibody titers (Figure 3). These results further confirm the temporal pattern using fixed serum dilutions. At Week 2, after the first immunization, antibody titers in the DNA primed groups were significantly higher than those in the two groups that received a protein vaccine as the prime (Figure 3A). By Week 6, which was two weeks after the 2nd immunization, LcrV-specific antibody titers in the DNA immunization groups were similar to those in the IFA-formulated recombinant LcrV protein group, but were still much higher than those in the group that received LcrV protein alone without IFA (Figure 3B). The same pattern was observed when the actual amount of LcrV-specific IgG (in μg/mL) was measured (Figure 3C) in addition to traditional end titration titers.


Pilot Study on the Use of DNA Priming Immunization to Enhance Y. pestis LcrV-Specific B Cell Responses Elicited by a Recombinant LcrV Protein Vaccine.

Li W, Wang S, Lu S - Vaccines (Basel) (2013)

V-specific IgG responses induced by various V vaccine regimens in mice: codon optimized V DNA vaccine alone (V-DNA), V DNA vaccine prime followed by V protein boost formulated with IFA (V-DNA + Prot/IFA), V protein formulated with IFA (V-Prot/IFA), V protein alone (V-Prot), or empty DNA vaccine vector alone (Vector). Panels A and B: V-specific antibody titers were measured by ELISA against V protein in mouse sera collected at 2 weeks after the prime (1st immunization) (Panel A) or at 2 weeks after the boost (2nd immunization) (Panel B). Panel C: V-specific IgG concentrations at 2 weeks after the boost (2nd) immunization. Each bar represents the mean V-specific IgG titers or concentrations in each group of 5 mice with standard error. Statistically significant differences (p < 0.05) are indicated as “*”, “#” or “^” when comparing V-DNA, V-DNA + Prot/IFA, and V-Prot/IFA groups.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4494201&req=5

vaccines-02-00036-f003: V-specific IgG responses induced by various V vaccine regimens in mice: codon optimized V DNA vaccine alone (V-DNA), V DNA vaccine prime followed by V protein boost formulated with IFA (V-DNA + Prot/IFA), V protein formulated with IFA (V-Prot/IFA), V protein alone (V-Prot), or empty DNA vaccine vector alone (Vector). Panels A and B: V-specific antibody titers were measured by ELISA against V protein in mouse sera collected at 2 weeks after the prime (1st immunization) (Panel A) or at 2 weeks after the boost (2nd immunization) (Panel B). Panel C: V-specific IgG concentrations at 2 weeks after the boost (2nd) immunization. Each bar represents the mean V-specific IgG titers or concentrations in each group of 5 mice with standard error. Statistically significant differences (p < 0.05) are indicated as “*”, “#” or “^” when comparing V-DNA, V-DNA + Prot/IFA, and V-Prot/IFA groups.
Mentions: The temporal pattern of antibody responses was measured using a fixed serum dilution; therefore, additional ELISA studies were conducted to measure actual antibody titers (Figure 3). These results further confirm the temporal pattern using fixed serum dilutions. At Week 2, after the first immunization, antibody titers in the DNA primed groups were significantly higher than those in the two groups that received a protein vaccine as the prime (Figure 3A). By Week 6, which was two weeks after the 2nd immunization, LcrV-specific antibody titers in the DNA immunization groups were similar to those in the IFA-formulated recombinant LcrV protein group, but were still much higher than those in the group that received LcrV protein alone without IFA (Figure 3B). The same pattern was observed when the actual amount of LcrV-specific IgG (in μg/mL) was measured (Figure 3C) in addition to traditional end titration titers.

Bottom Line: However, there is limited information on the mechanism of this effect.Previously, we demonstrated that a DNA vaccine expressing LcrV antigen can protect mice from lethal mucosal challenge.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA. wei.li@umassmed.edu.

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.

No MeSH data available.


Related in: MedlinePlus