Enhanced Immunogenicity of an HIV-1 DNA Vaccine Delivered with Electroporation via Combined Intramuscular and Intradermal Routes

Abstract

It is accepted that an effective prophylactic HIV-1 vaccine is likely to have the greatest impact on viral transmission rates. As previous reports have implicated DNA-priming, protein boost regimens to be efficient activators of humoral responses, we sought to optimize this regimen to further augment vaccine immunogenicity. Here we evaluated single versus concurrent intradermal Using an alternative and larger animal model, the rabbit, we found the concurrent DNA-priming strategy followed by s.c. protein boosting to again be capable of eliciting high-avidity humoral responses and to also be able to neutralize HIV-1 pseudoviruses from diverse clades (clades A, B, and C). Taken together, we show that concurrent multiple-route DNA vaccinations induce strong cellular immunity, in addition to potent and high-avidity humoral immune responses. IMPORTANCEThe route of vaccination has profound effects on prevailing immune responses. Due to the insufficient immunogenicity and protection of current DNA delivery strategies, we evaluated concurrent DNA delivery via simultaneous administration of plasmid DNA by the i.m. and i.d. routes. The rationale behind this study was to provide clear evidence of the utility of concurrent vaccinations for an upcoming human clinical trial. Furthermore, this work will guide future preclinical studies by evaluating the use of model antigens and plasmids for prime-boost strategies. This paper will be of interest not only to virologists and vaccinologists working in the HIV field but also to researchers working in other viral vaccine settings and, critically, to the wider field of vaccine delivery.

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“…Sera, feces, and vaginal washes were collected on days 0, 14, 28, and 42 and treated as described previously for subsequent ELISA-based analyses (14). Affinity assays were performed by ELISA as described by Mann et al (15). Serum CXCL13 levels were determined in 10-fold diluted samples using a DuoSet ELISA Mouse CXCL13 Kit (R&D Systems).…”

Poly(Lactic Acid) Nanoparticles Targeting α5β1 Integrin as Vaccine Delivery Vehicle, a Prospective Study

“…After the addition of 1N H 2 SO 4 to stop the reaction, the optical densities (OD) at 450 nm and 630 nm were measured in a microplate reader. To estimate the avidity of the immunoglobulins, we have tested antibody/antigen binding resistance to 8 M urea using a published method [31]. A prerequisite step was to have serum dilutions giving an OD at 450 nm of between 1 and 1.5.…”

“…The plates were then washed three times with PBS/0.05% Tween-20 or PBS/0.05% Tween-20/urea 8 M. The last steps were performed as for the ELISA assays. According to Mann et al [31], the avidity index corresponds to OD450 of urea-treated samples/OD450 of PBS/0.05% Tween-20 samples.…”

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“…125 However, immunogenicity can now be improved with intradermal delivery using electroporation, a technique that applies transient electrical pulses to cells to increase the permeability of the cell membrane and allow the nucleic acid to enter, or administration in conjunction with molecular adjuvants, such as interleukin 12. 126,127 These adjustments encouraged stimulation of both the cellular and humoral arms of the immune system. 127 HVTN 087 was a Phase I trial designed to assess the effect of increasing doses of plasmid DNA IL-12 adjuvant in conjunction with an HIV-1 multiantigen DNA vaccine delivered via electroporation.…”