Immunization of rhesus macaques with a polyvalent DNA prime/protein boost human immunodeficiency virus type 1 vaccine elicits protective antibody response against simian human immunodeficiency virus of R5 phenotype

Abstract

The immunogenicity of a poylvalent HIV-1 vaccine comprised of Env antigens from primary R5 isolates was evaluated in rhesus macaques. DNA vaccines encoding four Env antigens from multiple HIV-1 subtypes and HIV-1 Gag antigen from a single subtype elicited a persistent level of binding antibodies to gp120 from multiple HIV-1 isolates that were markedly enhanced following boosting with homologous gp120 proteins in QS-21 adjuvant irrespective of the route of DNA immunization. These sera neutralized homologous and, to a lesser degree, heterologous HIV-1 isolates. Four of the six immunized animals were completely protected following rectal challenge with a SHIV encoding Env from HIV-1(Ba-L), whereas the virus load was reduced in the remaining animals compared to naïve controls. Hence priming with DNA encoding Env antigens from multiple HIV-1 clades followed by boosting with homologous Env proteins elicits anti-HIV-1 immune responses capable of protecting macaques against mucosal transmission of R5 tropic SHIV isolate.

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].…”

“…Serum and PBMC samples were collected at Study Weeks 0, 2,4,6,12,14,16,20,22,24,28,30,32,36 and 52 to measure antibody and CMI responses. All volunteers were recruited and enrolled in the Clinical Vaccine Research Unit, UMMS.…”

The safety and tolerability of an HIV-1 DNA prime–protein boost vaccine (DP6-001) in healthy adult volunteers

“…Recently, we reported that a novel multi-gene, polyvalent DNA prime-recombinant protein boost HIV vaccine formulation, DP6-001, elicited strong and balanced humoral and cell-mediated immunity in healthy, HIV-1-negative adult subjects [1]. Preclinical testing of DP6-001 demonstrated no significant adverse reactions in either rabbits or non-human primates despite the induction of robust immunity [2,3]. Previously tested HIV DNA vaccines have demonstrated excellent human safety profiles [4][5][6][7][8][9].…”

DNA Vaccines: How Much Have We Accomplished In The Last 25 Years?

“…In this approach, the immune system is primed by administering the antigen of interest by one method (e.g DNA vaccine) and then boosted by a different one that delivers the same antigen (e.g recombinant protein, recombinant virus). A vast number of experiments have been performed in mice and non-human primates [139] and these strategies are already into clinical trials [140]. Detailed reviews on heterologous prime-boost strategies have been published elsewhere [3,[141][142][143].…”