Abstract
A plasmid DNA vaccine is able to induce both humoral and cellular immune responses; however, the kinetic change of the Th1/Th2 response, antibody avidity, cytokine secretion, and neutralization activity after different priming and boosting strategies have not been evaluated. A plasmid DNA, designated pCBD2 and previously shown to efficiently induce an immune response very similar to that by a wild type virus, was evaluated kinetically in this study. Our results suggest that a DNA vaccine delivered by the gene gun (gg) route produced higher and longer DENV-2-specific antibody titers than those induced through the intramuscular (im) route. Although the gg group induced a Th2 response and im delivery induced a Th1 response, priming by gg delivery, followed by a boosting by im delivery, did not shift the immune response from a Th2 to Th1 response. Furthermore, the antibody avidity (AI) measured by ELISA demonstrated a gradual increase of AI from low (AI range from 6.8% - 9.6%) on day 42 to high (AI value > 30) on day 119 in all but the gene-gun immunization group, in which an AI value of 23 was observed. Although there was lower avidity in the gg group, the mice sera from all three groups of mice demonstrated significant neutralization activity. This is the first report about the kinetics of immunogenicity of a DNA vaccine through different administration strategies, which suggests that gene gun delivery of a DNA vaccine can induce an immune response containing both neutralizing and nonneutralizing antibodies at high titers important for neutralization.
Highlights
Dengue is a mosquito-borne viral disease in humans and is a significant public health threat in the tropics and subtropics, where billions of people are at risk and an estimated 100 million new infections occur each year [1]
At no time were any statistically significant differences seen between groups in the antibody responses of mice when DENV-2 infected cells or when a Virus-Like Particle (VLP) was used as the antigen for ELISA
The results suggested that gene-gun delivery of a DNA vaccine induced a higher and longer duration of DENV-2-specific antibody responses compared to im delivery
Summary
Dengue is a mosquito-borne viral disease in humans and is a significant public health threat in the tropics and subtropics, where billions of people are at risk and an estimated 100 million new infections occur each year [1]. There are four dengue virus serotypes, named dengue virus serotype 1 (DENV-1) through dengue virus serotype 4 (DENV-4). These viruses form an antigenically distinct subgroup within the flavivirus family [2]. One infected by any of these viruses may be either asymptomatic or inflicted with a self-limited febrile illness known as dengue fever (DF). Despite the magnitude of public health implications
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