Innate Molecular and Cellular Signature in the Skin Preceding Long-Lasting T Cell Responses after Electroporated DNA Vaccination

Adam, Lucille; Tchitchek, Nicolas; Todorova, Biliana; Rosenbaum, Pierre; Joly, Charles-Alexandre; Poux, Candice; Chapon, Catherine; Spetz, Anna-Lena; Ustav, Mart; Grand, Roger Le; Martinon, Frédéric

doi:10.4049/jimmunol.1900517

Cited by 12 publications

(10 citation statements)

References 102 publications

(94 reference statements)

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“…Although the neoantigen-specific immune response in the periphery of tumor-bearing mice was not a clear biomarker of the antitumor response it suggests that the quality of the responses rather than the site of vaccination, ID vs. IM, is an important determinant. Our preliminary data identify some differences in the immune responses between C20-ID and C20-IM, however, we cannot exclude that other electrical conditions may favor neoantigen-specific CD8 + IFN + T cells immune response in the ID protocol 47 , 48 . The lack of antitumor activity of NCV with αPD1 in this therapeutic protocol is in line with previous evidence showing that treatment with αPD1 before vaccination had a negative impact on tumor growth 49 .…”

Section: Discussionmentioning

confidence: 72%

Neoantigen cancer vaccine augments anti-CTLA-4 efficacy

Salvatori¹,

Lione²,

Compagnone

et al. 2022

npj Vaccines

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Immune checkpoint inhibitors (ICI) based on anti-CTLA-4 (αCTLA-4) and anti-PD1 (αPD1) are being tested in combination with different therapeutic approaches including other immunotherapies such as neoantigen cancer vaccines (NCV). Here we explored, in two cancer murine models, different therapeutic combinations of ICI with personalized DNA vaccines expressing neoantigens and delivered by electroporation (EP). Anti-cancer efficacy was evaluated using vaccines with or without CD4 epitopes. Therapeutic DNA vaccines showed synergistic effects in different therapeutic protocols including established large tumors. Flow cytometry (FC) was utilized to measure CD8, CD4, Treg, and switched B cells as well as neoantigen-specific immune responses, which were also measured by IFN-γ ELIspot. Immune responses were augmented in combination with αCTLA4 but not with αPD1 in the MC38 tumor-bearing mice, significantly impacting tumor growth. Similarly, neoantigen-specific T cell immune responses were enhanced in combined treatment with αCTLA-4 in the CT26 tumor model where large tumors regressed in all mice, while monotherapy with αCTLA-4 was less efficacious. In line with previous evidence, we observed an increased switched B cells in the spleen of mice treated with αCTLA-4 alone or in combination with NCV. These results support the use of NCV delivered by DNA-EP with αCTLA-4 and suggest a new combined therapy for clinical testing.

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Section: Discussionmentioning

confidence: 72%

Neoantigen cancer vaccine augments anti-CTLA-4 efficacy

Salvatori¹,

Lione²,

Compagnone

et al. 2022

npj Vaccines

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“…In the Zika virus outbreak in 2015, a Zika DNA vaccine delivered via electroporation was developed into a phase 1 clinical trial within 7 months [15]. EP combined with DNA vaccination greatly increases the efficacy of DNA vaccines [16][17][18]. Because of the successful results of animal experiments after DNA vaccination with EP, many different electroporation devices for humans have been developed, including Cellectra1 (Inovio Inc., USA) and TriGrid1 (Ichor Medical Systems, USA).…”

Section: Introductionmentioning

confidence: 99%

DNA vaccination induced protective immunity against SARS CoV-2 infection in hamsterss

et al. 2021

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The development of efficient vaccines against COVID-19 is an emergent need for global public health. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major target for the COVID-19 vaccine. To quickly respond to the outbreak of the SARS-CoV-2 pandemic, a nucleic acid-based vaccine is a novel option, beyond the traditional inactivated virus vaccine or recombinant protein vaccine. Here, we report a DNA vaccine containing the spike gene for delivery via electroporation. The spike genes of SARS-CoV and SARS-CoV-2 were codon optimized for mammalian cell expression and then cloned into mammalian cell expression vectors, called pSARS-S and pSARS2-S, respectively. Spike protein expression was confirmed by immunoblotting after transient expression in HEK293T cells. After immunization, sera were collected for antigen-specific antibody and neutralizing antibody titer analyses. We found that both pSARS-S and pSARS2-S immunization induced similar levels of antibodies against S2 of SARS-CoV-2. In contrast, only pSARS2-S immunization induced antibodies against the receptor-binding domain of SARS-CoV-2. We further found that pSARS2-S immunization, but not pSARS-S immunization, could induce very high titers of neutralizing antibodies against SARS-CoV-2. We further analyzed SARS-CoV-2 S protein-specific T cell responses and found that the immune responses were biased toward Th1. Importantly, pSARS2-S immunization in hamsters could induce protective immunity against SARS-CoV-2 challenge in vivo. These data suggest that DNA vaccination could be a promising approach for protecting against COVID-19.

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“…Cellular immunity will need to be explored thoroughly to enable better prediction of vaccine immunogenicity. As already discussed, local cellular events shape subsequent protective responses [36,[211][212][213]. Thus, their characterization can provide a way to rapidly assess the quality of vaccine-induced immunity.…”

Section: Defining New Correlates Of Protectionmentioning

confidence: 96%

“…As mentioned previously, early local events in the skin following immunization can shape subsequent immune responses and vaccine efficacy [36,[211][212][213]. In other respects, the acquisition of immune memory characterizes adaptive responses and is of critical importance for vaccines to confer long-lasting protection.…”

Section: Deciphering Mechanisms That Underly Immune Protective Responsesmentioning

confidence: 96%

“…In another study, Adam et al investigated the early mechanisms that occur in the skin after intradermal injection and electroporation of SIV immunogens in Cynomolgus macaques. They used flow cytometry, cytokine profiling, and transcriptomics of skin cells to demonstrate that electroporation has a strong adjuvant effect mediated by inflammatory cell recruitment and LC mobilization [212]. Finally, studying how the vaccine regimen influences immune signatures could be critical to improving vaccination strategies in human populations.…”

Section: Improving Vaccine Formulation and Administrationmentioning

confidence: 99%

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Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

et al. 2021

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Vaccines represent one of the major advances of modern medicine. Despite the many successes of vaccination, continuous efforts to design new vaccines are needed to fight “old” pandemics, such as tuberculosis and malaria, as well as emerging pathogens, such as Zika virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccination aims at reaching sterilizing immunity, however assessing vaccine efficacy is still challenging and underscores the need for a better understanding of immune protective responses. Identifying reliable predictive markers of immunogenicity can help to select and develop promising vaccine candidates during early preclinical studies and can lead to improved, personalized, vaccination strategies. A systems biology approach is increasingly being adopted to address these major challenges using multiple high-dimensional technologies combined with in silico models. Although the goal is to develop predictive models of vaccine efficacy in humans, applying this approach to animal models empowers basic and translational vaccine research. In this review, we provide an overview of vaccine immune signatures in preclinical models, as well as in target human populations. We also discuss high-throughput technologies used to probe vaccine-induced responses, along with data analysis and computational methodologies applied to the predictive modeling of vaccine efficacy.

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Innate Molecular and Cellular Signature in the Skin Preceding Long-Lasting T Cell Responses after Electroporated DNA Vaccination

Cited by 12 publications

References 102 publications

Neoantigen cancer vaccine augments anti-CTLA-4 efficacy

Neoantigen cancer vaccine augments anti-CTLA-4 efficacy

DNA vaccination induced protective immunity against SARS CoV-2 infection in hamsterss

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

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