Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials

Abstract

Plasmid DNA vaccines have been licensed for use in domesticated animals because of their excellent immunogenicity, but none have yet been licensed for use in humans. Here we report a retrospective analysis of 1218 healthy human volunteers enrolled in 10 phase I clinical trials in which DNA plasmids encoding HIV antigens were administered. Elicited T-cell immune responses were quantified by validated intracellular cytokine staining (ICS) stimulated with HIV peptide pools. HIV-specific binding and neutralizing antibody activities were also analyzed using validated assays. Results showed that, in the absence of adjuvants and boosting with alternative vaccines, DNA vaccines elicited CD8+ and CD4+ T-cell responses in an average of 13.3% (95% CI: 9.8% to 17.8%) and 37.7% (95% CI: 31.9% to 43.8%) of vaccine recipients, respectively. Three vaccinations (versus 2) improved the proportion of subjects with antigen-specific CD8+ responses (p=0.02), as did increased DNA dosage (p=0.007). Furthermore, female gender and participants having a lower Body Mass Index were independently associated with higher CD4+ T-cell response rate (p=0.001 and p=0.008, respectively). These vaccines elicited minimal neutralizing and binding antibody responses. These findings of the immunogenicity of HIV DNA vaccines in humans can provide guidance for future clinical trials.

CD71 targeting boosts immunogenicity of sublingually delivered influenza haemagglutinin antigen and protects against viral challenge in mice

“…We assessed the effect of Tf-HA compared to sublingual HA alone in animals that had previously been immunized with DNA vaccines. DNA vaccines are a promising technology that are highly effective in small animal models, but have failed to deliver on this promise in clinical trials [30]. However, they can provide a useful priming immunisation, especially in the induction of T cells which have been proposed to be an important component of a universal influenza vaccine that is cross-protective against multiple strains [15].…”

Innovations in HIV-1 Vaccine Design

“…DNA-based vaccines, first developed in the early 1990s, are now experiencing a resurgence because of their excellent immunogenicity in animals and ease of manufacture, scalability, and storage. 124 Early studies revealed that naked DNA plasmid HIV-1 vaccines were poorly immunogenic in humans. 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.…”

Engineering DNA vaccines against infectious diseases

“…To date, there is no licensed DNA vaccine for use in humans [59,60]. The scientific community has high expectations for DNA vaccine use because of the following reasons: (1) the ability to control the transcribed and translated product, thereby controlling the ability of the antigen to not revert to a virulent pathogenic form;…”