Intradermal HIV-1 DNA Immunization Using Needle-Free Zetajet Injection Followed by HIV-Modified Vaccinia Virus Ankara Vaccination Is Safe and Immunogenic in Mozambican Young Adults: A Phase I Randomized Controlled Trial

Viegas, Edna; Tembe, Nelson; Nilsson, Charlotta; Meggi, Bindiya; Maueia, Cremildo; Augusto, Orvalho; Stout, Richard; Scarlatti, Gabriella; Ferrari, Guido; Earl, Patricia L.; Wahrén, Britta; Andersson, Sören; Robb, Merlin L.; Nafissa, Osman; Biberfeld, Gunnel; Jani, Ilesh; Sandström, Eric

doi:10.1089/aid.2017.0121

Cited by 17 publications

(12 citation statements)

References 43 publications

(77 reference statements)

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“…The present study builds on previous data from trials in Sweden, Tanzania and Mozambique [13, 14, 26], and aimed to determine the optimal prime boost regimen to take forward to efficacy testing by evaluating whether (i) ID EP with the Derma Vax (Cellectis) device would boost responses to 600μg HIV-DNA, (ii) combining the DNA plasmids in a single injection would compromise responses, and (iii) combining GLA-AF adjuvanted CN54rg140 protein with the HIV-MVA would improve the magnitude or functionality of humoral responses. We chose to address these questions in a single trial using a factorial design.…”

Section: Introductionmentioning

confidence: 65%

Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design

et al. 2018

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BackgroundWe evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique.MethodsHealthy HIV-uninfected adults (N = 191) were randomized twice; first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL [6mg/mL] plus EP). Second the same volunteers received 108 pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo.ResultsVaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-γ ELISpot response rate to either Gag or Env was 97%. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66% group I vs. 86% group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95%, 99%, 79%, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, p<0.001) and subtype C gp140 (24300 versus 2700, p<0.001) Env protein. At relatively low titers, neutralizing antibody responses using the TZM-bl assay were more frequent in vaccinees given adjuvanted protein boost.ConclusionIntradermal electroporation increased DNA-induced Gag response rates but did not show an impact on Env-specific responses nor on the magnitude of responses. Co-administration of HIV-MVA with rgp140/GLA-AF significantly enhanced antibody responses.

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Section: Introductionmentioning

confidence: 65%

Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design

et al. 2018

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“…Many of these more novel jet injectors are being assessed in clinical trials and have shown comparable immunogenicity to needle and syringe techniques. Devices assessed in clinical trials include the Injex30 (Injex Equidyne, Oxford, UK), Biojector 2000 (NCT00109629) (Bioject, USA), Bioject ZetaJet (NCT01407497) (Bioject, USA), the PharmaJet Stratis (NCT01688921) (PharmaJet, Golden, CO, USA), and the TriGrid electroporation systems (NCT02589795) (Ichor Medical Systems, San Diego, CA, USA) [ 160 , 161 , 162 , 163 , 164 , 165 ].…”

Section: Vaccination Into the Dermal Compartment Without Needle Anmentioning

confidence: 99%

“…For instance, Genetronics Inc (San Diego, CA, USA) patented an injector pen, which uses a spring mechanism to apply needle-free intradermal injection of a liquid [ 176 ]. The Injex30 provided comparable antibody titres to subcutaneous N&S injection in a study with mice vaccinated against hepatitis B surface antigen [ 163 ]. A pyro-drive jet injector (Actranza™, DAICEL Corporation, Osaka, Japan) has been shown to allow for the adjustment of injection depth and has demonstrated potential to induce antibodies in rats [ 177 ].…”

Section: Vaccination Into the Dermal Compartment Without Needle Anmentioning

confidence: 99%

Vaccination into the Dermal Compartment: Techniques, Challenges, and Prospects

Hettinga

Carlisle

2020

Vaccines

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In 2019, an ‘influenza pandemic’ and ‘vaccine hesitancy’ were listed as two of the top 10 challenges to global health by the WHO. The skin is a unique vaccination site, due to its immune-rich milieu, which is evolutionarily primed to respond to challenge, and its ability to induce both humoral and cellular immunity. Vaccination into this dermal compartment offers a way of addressing both of the challenges presented by the WHO, as well as opening up avenues for novel vaccine formulation and dose-sparing strategies to enter the clinic. This review will provide an overview of the diverse range of vaccination techniques available to target the dermal compartment, as well as their current state, challenges, and prospects, and touch upon the formulations that have been developed to maximally benefit from these new techniques. These include needle and syringe techniques, microneedles, DNA tattooing, jet and ballistic delivery, and skin permeabilization techniques, including thermal ablation, chemical enhancers, ablation, electroporation, iontophoresis, and sonophoresis.

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“…The effects of routes of vaccination have been investigated mostly with a focus on differences in the induced humoral immune responses (28) or cellular CD8 T cell responses (29)(30)(31). However, only a few studies have focused on CD4 T cells, and they demonstrated increased levels of Tfh cells after intradermal vaccination (32).…”

Section: Discussionmentioning

confidence: 99%

Modulation of Vaccine-Induced CD4 T Cell Functional Profiles by Changes in Components of HIV Vaccine Regimens in Humans

Pissani

Schulte

Eller

et al. 2018

J Virol

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To date, six vaccine strategies have been evaluated in clinical trials for their efficacy at inducing protective immune responses against HIV infection. However, only the ALVAC-HIV/AIDSVAX B/E vaccine (RV144 trial) has demonstrated protection, albeit modestly (31%; = 0.03). One potential correlate of protection was a low-frequency HIV-specific CD4 T cell population with diverse functionality. Although CD4 T cells, particularly T follicular helper (Tfh) cells, are critical for effective antibody responses, most studies involving HIV vaccines have focused on humoral immunity or CD8 T cell effector responses, and little is known about the functionality and frequency of vaccine-induced CD4 T cells. We therefore assessed responses from several phase I/II clinical trials and compared them to responses to natural HIV-1 infection. We found that all vaccines induced a lower magnitude of HIV-specific CD4 T cell responses than that observed for chronic infection. Responses differed in functionality, with a CD40 ligand (CD40L)-dominated response and more Tfh cells after vaccination, whereas chronic HIV infection provoked tumor necrosis factor alpha (TNF-α)-dominated responses. The vaccine delivery route further impacted CD4 T cells, showing a stronger Th1 polarization after dendritic cell delivery than after intramuscular vaccination. In prime/boost regimens, the choice of prime and boost influenced the functional profile of CD4 T cells to induce more or less polyfunctionality. In summary, vaccine-induced CD4 T cell responses differ remarkably between vaccination strategies, modes of delivery, and boosts and do not resemble those induced by chronic HIV infection. Understanding the functional profiles of CD4 T cells that best facilitate protective antibody responses will be critical if CD4 T cell responses are to be considered a clinical trial go/no-go criterion. Only one HIV-1 candidate vaccine strategy has shown protection, albeit marginally (31%), against HIV-1 acquisition, and correlates of protection suggested that a multifunctional CD4 T cell immune response may be important for this protective effect. Therefore, the functional phenotypes of HIV-specific CD4 T cell responses induced by different phase I and phase II clinical trials were assessed to better show how different vaccine strategies influence the phenotype and function of HIV-specific CD4 T cell immune responses. The significance of this research lies in our comprehensive comparison of the compositions of the T cell immune responses to different HIV vaccine modalities. Specifically, our work allows for the evaluation of vaccination strategies in terms of their success at inducing Tfh cell populations.

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Intradermal HIV-1 DNA Immunization Using Needle-Free Zetajet Injection Followed by HIV-Modified Vaccinia Virus Ankara Vaccination Is Safe and Immunogenic in Mozambican Young Adults: A Phase I Randomized Controlled Trial

Cited by 17 publications

References 43 publications

Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design

Optimizing the immunogenicity of HIV prime-boost DNA-MVA-rgp140/GLA vaccines in a phase II randomized factorial trial design

Vaccination into the Dermal Compartment: Techniques, Challenges, and Prospects

Modulation of Vaccine-Induced CD4 T Cell Functional Profiles by Changes in Components of HIV Vaccine Regimens in Humans

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