DNA Immunization

Wang, Shixia; Lu, Shan

doi:10.1002/9780471729259.mc1803s31

Cited by 20 publications

(27 citation statements)

References 108 publications

(157 reference statements)

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“…After optimization of the immunogens, the immunization scheme, and the delivery vehicles, we proceeded to optimize the process of electroporation because this can greatly improve the performance of DNA vaccines 48 , 71 . The efficacy of electroporation is determined by the combination of several parameters, such as voltage, duration of the pulses, pulse polarity, and configuration of the electrodes.…”

Section: Resultsmentioning

confidence: 99%

“…Specifcially, we tested different routes of DNA delivery, adjusted the electroporation parameters, applied different prime-boost regimens, and added an adjuvant that promotes a cellular immune response. Such systematic optimization was shown to considerably improve the immune response to DNA immunization, including its cellular component 48 , 49 . Indeed, we achieved significant enhancement of the anti-RT immune response.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Codon optimization and improved delivery/immunization regimen enhance the immune response against wild-type and drug-resistant HIV-1 reverse transcriptase, preserving its Th2-polarity

Latanova

Petkov

Kilpeläinen

et al. 2018

Sci Rep

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DNA vaccines require a considerable enhancement of immunogenicity. Here, we optimized a prototype DNA vaccine against drug-resistant HIV-1 based on a weak Th2-immunogen, HIV-1 reverse transcriptase (RT). We designed expression-optimized genes encoding inactivated wild-type and drug-resistant RTs (RT-DNAs) and introduced them into mice by intradermal injections followed by electroporation. RT-DNAs were administered as single or double primes with or without cyclic-di-GMP, or as a prime followed by boost with RT-DNA mixed with a luciferase-encoding plasmid (“surrogate challenge”). Repeated primes improved cellular responses and broadened epitope specificity. Addition of cyclic-di-GMP induced a transient increase in IFN-γ production. The strongest anti-RT immune response was achieved in a prime-boost protocol with electroporation by short 100V pulses done using penetrating electrodes. The RT-specific response, dominated by CD4+ T-cells, targeted epitopes at aa 199–220 and aa 528–543. Drug-resistance mutations disrupted the epitope at aa 205–220, while the CTL epitope at aa 202–210 was not affected. Overall, multiparametric optimization of RT strengthened its Th2- performance. A rapid loss of RT/luciferase-expressing cells in the surrogate challenge experiment revealed a lytic potential of anti-RT response. Such lytic CD4+ response would be beneficial for an HIV vaccine due to its comparative insensitivity to immune escape.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Codon optimization and improved delivery/immunization regimen enhance the immune response against wild-type and drug-resistant HIV-1 reverse transcriptase, preserving its Th2-polarity

Latanova

Petkov

Kilpeläinen

et al. 2018

Sci Rep

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show abstract

“…Finally, we used a DNA prime, protein boost approach to immunization(61). Interactions between the prime and the boost are not well understood, and new findings may offer opportunities to enhance the potency of the response without altering specificity(62).…”

Section: Discussionmentioning

confidence: 99%

Vaccine focusing to cross-subtype HIV-1 gp120 variable loop epitopes

Cardozo

Wang

Jiang

et al. 2014

Vaccine

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We designed synthetic, epitope-focused immunogens that preferentially display individual neutralization epitopes targeted by cross-subtype anti-HIV V3 loop neutralizing monoclonal antibodies (mAbs). Vaccination of rabbits with these immunogens resulted in the elicitation of distinct polyclonal serum Abs that exhibit cross-subtype neutralization specificities mimicking the mAbs that guided the design. Our results prove the principle that a predictable range of epitope-specific polyclonal cross-subtype HIV-1 neutralizing Abs can be intentionally elicited in mammals by vaccination. The precise boundaries of the epitopes and conformational flexibility in the presentation of the epitopes in the immunogen appeared to be important for successful elicitation. This work may serve as a starting point for translating the activities of human broadly neutralizing anti-HIV-1 monoclonal antibodies (bNAbs) into matched immunogens that can contribute to an efficacious HIV-1 vaccine.

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“…DNA immunizations were performed using a Helios Gene Gun (Bio-Rad) as described before 21 following the schedule shown in Fig. 1 .…”

Section: Methodsmentioning

confidence: 99%

The dynamics of immunoglobulin V-gene usage and clonotype expansion in mice after prime and boost immunizations as analyzed by NGS

Farfán-Arribas

Liu

Wang

et al. 2017

Human Vaccines & Immunotherapeutics

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In the current study, an improved NGS approach was developed to study the B-cell repertoire evolution in a simple mouse immunization model including only two DNA immunizations. The combination of 5′RACE and Ion Torrent long reads enabled unbiased immunoglobulin repertoire analysis even from small amounts of peripheral mouse blood. The B-cell population expanded by the vaccine displayed a relatively strong clonality. Upon priming with the first vaccine dose, we observed a consistent pattern of V-segment gene and CDR3 usage (public specificities). Interestingly, this pattern diversified with the second dose of immunization —it was relatively different in individual mice in spite of having received the same vaccine regimen (private specificities). Nevertheless, there were several instances in which the same public V-segment genes and CDR3s that were expanded after the first dose were further amplified after the second immunization. Taken together, it appears that the major clonotypes expanded by vaccination were originally a homogeneous subset that later diversified after a second dose leading to diverse “private” clonal compositions in different mice. These results established a new platform valuable to perform longitudinal analyses of the Ig germline gene usage and clonotype evolution throughout an immunization regimen in a commonly used animal model.

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DNA Immunization

Cited by 20 publications

References 108 publications

Codon optimization and improved delivery/immunization regimen enhance the immune response against wild-type and drug-resistant HIV-1 reverse transcriptase, preserving its Th2-polarity

Codon optimization and improved delivery/immunization regimen enhance the immune response against wild-type and drug-resistant HIV-1 reverse transcriptase, preserving its Th2-polarity

Vaccine focusing to cross-subtype HIV-1 gp120 variable loop epitopes

The dynamics of immunoglobulin V-gene usage and clonotype expansion in mice after prime and boost immunizations as analyzed by NGS

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