Preclinical evaluation of cellular immune responses elicited by a polyvalent DNA prime/protein boost HIV-1 vaccine

Abstract

While DNA vaccines have been shown to prime cellular immune responses, levels are often low in nonhuman primates or humans. Hence, efforts have been directed toward boosting responses by combining DNA with different vaccination modalities. To this end, a polyvalent DNA prime/protein boost vaccine, consisting of codon optimized HIV-1 env (A, B, C, E) and gag (C) and homologous gp120 proteins in QS-21, was evaluated in rhesus macaques and BALB/c mice. Humoral and cellular responses, detected following DNA immunization, were increased following protein boost in macaques and mice. In dissecting cellular immune responses in mice, protein-enhanced responses were found to be mediated by CD4+ and CD8+ T cells with a Th1 cytokine bias. Our study reveals that, in addition to augmenting humoral responses, protein boosting of DNA-primed animals augments cellular immune responses mediated by CD8+ CTL, CD4+ T-helper cells and Th1 cytokines; thus, offering much promise in controlling HIV-1 in vaccinees.

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

“…Recently, we demonstrated that a DNA prime-protein boost immunization strategy was effective in eliciting humoral and CMI responses in both small animals and non-human primates, including sterilizing immunity in a non-pathogenic SHIV model [16][17][18]. Our preclinical study results also indicated that this combination vaccination approach, but not recombinant protein alone, was effective in eliciting NAbs against primary HIV isolates [19], a finding that has been confirmed subsequently by other independent studies [20][21][22][23][24][25][26].…”

“…Although significant progress has been made using DNA immunization to elicit HIV-1-specific CMI in small animals, non-human primates and humans over the past 15 years [12][13][14][15][16]18,[38][39][40][41], there has been no report of using Env DNA immunization to elicit broadly crossreactive antibodies in humans. Levels of anti-Env antibodies elicited in previous DNA vaccine clinical trials were either low or undetectable [42,43], nor was there a clear induction of NAbs against even sensitive viruses [14].…”

Replicating adenovirus vector prime/protein boost strategies for HIV vaccine development

“…Novel boosting immunogens will undoubtedly be needed to elicit broadly neutralizing antibodies. Further, as reported by others [106,107], boosting with protein can lead to increased and broader cellular and humoral immune responses. The studies reviewed to this point all were conducted with two replicating Ad-recombinant priming immunizations followed by two protein boosts.…”

CT043, a Protective Antigen That Induces a CD4+Th1 Response duringChlamydia trachomatisInfection in Mice and Humans

“…The DNA immunization approach was adopted, since conventional protein-based vaccines are usually limited in their ability to raise robust cell-mediated immune responses (33). Moreover, the DNA prime/protein boost regimen is known to elicit both cellular and humoral immunity and has been shown to be effective in vaccination experiments against different pathogens in small animals and nonhuman primates (5,26,39). Finally, DNA immunization could allow the elicitation of an immune response against conformational epitopes (1,32,38).…”