The relative immunogenicity of DNA vaccines delivered by the intramuscular needle injection, electroporation and gene gun methods

China-US Vaccine Research Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Vaccine (Impact Factor: 3.62). 05/2008; 26(17):2100-10. DOI: 10.1016/j.vaccine.2008.02.033
Source: PubMed


Immunogenicity of DNA vaccines varies significantly due to many factors including the inherent immunogenicity of the protein antigen encoded in the DNA vaccine, the optimal immune responses that can be achieved in different animal models and in humans with different genetic backgrounds and, to a great degree, the delivery methods used to administer the DNA vaccines. Based on published results, only the gene gun-mediated delivery approach has been able to elicit protective levels of immune responses in healthy, adult volunteers by DNA immunization alone without the use of another vaccine modality as a boost. Recent results from animal studies suggest that electroporation is also effective in eliciting high level immune responses. However, there have been no reports to identify the similarities and differences between these two leading physical delivery methods for DNA vaccines against infectious disease targets. In the current study, we compared the relative immunogenicity of a DNA vaccine expressing a hemagglutinin (HA) antigen from an H5N1 influenza virus in two animal models (rabbit and mouse) when delivered by either intramuscular needle immunization (IM), gene gun (GG) or electroporation (EP). HA-specific antibody, T cell and B cell responses were analyzed. Our results indicate that, overall, both the GG and EP methods are more immunogenic than the IM method. However, EP and IM stimulated a Th-1 type antibody response and the antibody response to GG was Th-2 dominated. These findings provide important information for the further selection and optimization of DNA vaccine delivery methods for human applications.

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Available from: Shan Lu, Sep 30, 2015
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    • "However, on their own DNA plasmid vaccines have exhibited very limited immunostimulatory capacity and often induced suboptimal immune responses. Recent advances in DNA delivery such as intramuscular, skin or intradermal electroporation (Selby et al., 2000; Widera et al., 2000; Brave et al., 2010; Vasan et al., 2011; Kopycinski et al., 2012) or use of other physical delivery methods such as gene gun and biojector devices (Drape et al., 2006; Wang et al., 2008a; Graham et al., 2013), together with concurrent use of cytokine adjuvants including IL-2, IL- 12, and IL-15 (Winstone et al., 2011; Kalams et al., 2012, 2013) have greatly improved the immunogenic potential of DNA vaccines . In particular, IL-12 was shown to significantly augment the frequency, magnitude and breadth of Gag-specific immune responses in healthy volunteers immunized with a recombinant DNA vaccine expressing HIV-1 Gag (Kalams et al., 2012, 2013). "
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    ABSTRACT: Development of an effective HIV/AIDS vaccine remains a big challenge, largely due to the enormous HIV diversity which propels immune escape. Thus novel vaccine strategies are targeting multiple variants of conserved antibody and T cell epitopic regions which would incur a huge fitness cost to the virus in the event of mutational escape. Besides immunogen design, the delivery modality is critical for vaccine potency and efficacy, and should be carefully selected in order to not only maximize transgene expression, but to also enhance the immuno-stimulatory potential to activate innate and adaptive immune systems. To date, five HIV vaccine candidates have been evaluated for efficacy and protection from acquisition was only achieved in a small proportion of vaccinees in the RV144 study which used a canarypox vector for delivery. Conversely, in the STEP study (HVTN 502) where human adenovirus serotype 5 (Ad5) was used, strong immune responses were induced but vaccination was more associated with increased risk of HIV acquisition than protection in vaccinees with pre-existing Ad5 immunity. The possibility that pre-existing immunity to a highly promising delivery vector may alter the natural course of HIV to increase acquisition risk is quite worrisome and a huge setback for HIV vaccine development. Thus, HIV vaccine development efforts are now geared toward delivery platforms which attain superior immunogenicity while concurrently limiting potential catastrophic effects likely to arise from pre-existing immunity or vector-related immuno-modulation. However, it still remains unclear whether it is poor immunogenicity of HIV antigens or substandard immunological potency of the safer delivery vectors that has limited the success of HIV vaccines. This article discusses some of the promising delivery vectors to be harnessed for improved HIV vaccine efficacy.
    Frontiers in Microbiology 08/2014; 5:439. DOI:10.3389/fmicb.2014.00439 · 3.99 Impact Factor
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    • "The relative immunogenicity of DNA vaccines expressing HBs-L and HBs-L(T) were examined in Balb/C mice by electroporation as previous described [34]. The same amount of DNA vaccine expressing either HBs-L or HBs-L(T) was administered individually to mice at Weeks 0, 2, and 4. Compared to the HBs-L DNA vaccine, the HBs-L(T) DNA vaccine induced HBsAg-specific antibody responses earlier and with higher titers (Fig 2). "
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    ABSTRACT: Although the use of recombinant hepatitis B virus surface (HBsAg) protein vaccine has successfully reduced global hepatitis B infection, there are still a number of vaccine recipients who do not develop detectable antibody responses. Various novel vaccination approaches, including DNA vaccines, have been used to further improve the coverage of vaccine protection. Our previous studies demonstrated that HBsAg-based DNA vaccines could induce both humoral and CMI responses in experimental animal models. However, one form of the the HBsAg antigen, the large S antigen (HBs-L), expressed by DNA vaccine, was not sufficiently immunogenic in eliciting antibody responses. In the current study, we produced a modified large S antigen DNA vaccine, HBs-L(T), which has a truncated N-terminal sequence in the pre-S1 region. Compared to the original HBs-L DNA vaccine, the HBs-L(T) DNA vaccine improved secretion in cultured mammalian cells and generated significantly enhanced HBsAg-specific antibody and B cell responses. Furthermore, this improved HBsL DNA vaccine, along with other HBsAg-expressing DNA vaccines, was able to maintain predominantly Th1 type antibody responses while recombinant HBsAg protein vaccines produced in either yeast or CHO cells elicited mostly Th2 type antibody responses. Our data indicate that HBsAg DNA vaccines with improved immunogenicity offer a useful alternative choice to recombinant protein-based HBV vaccines, particularly for therapeutic purposes against chronic hepatitis infection where immune tolerance led to poor antibody responses to S antigens.
    PLoS ONE 07/2012; 7(7):e41573. DOI:10.1371/journal.pone.0041573 · 3.23 Impact Factor
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    • "Although the mechanism underlying which is unclear, we think the HA may play roles in this discrepancy between the results of Heinen et al.’s and ours. Another possible reason should be taken into consideration is that gene gun immunization induces more strong immune response that the conventional needle injection method, which was used in Heinen et al.’s study [37]. It is necessary to study whether the DNA vaccines we developed here will confer protection in pig models. "
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