DNA vaccination in rhesus macaques induces potent immune responses and decreases acute and chronic viremia after SIVmac251 challenge

Abstract

Optimized plasmid DNAs encoding the majority of SIVmac239 proteins and delivered by electroporation (EP) elicited strong immune responses in rhesus macaques. Vaccination decreased viremia in both the acute and chronic phases of infection after challenge with pathogenic SIVmac251. Two groups of macaques were vaccinated with DNA plasmids producing different antigen forms, ''native'' and ''modified,'' inducing distinct immune responses. Both groups showed significantly lower viremia during the acute phase of infection, whereas the group immunized with the native antigens showed better protection during the chronic phase (1.7 log decrease in virus load, P ‫؍‬ 0.009). Both groups developed strong cellular and humoral responses against the DNA vaccine antigens, which included Gag, Pol, Env, Nef, and Tat. Vaccination induced both central memory and effector memory T cells that were maintained at the day of challenge, suggesting the potential for rapid mobilization upon virus challenge. The group receiving the native antigens developed higher and more durable anti-Env antibodies, including neutralizing antibodies at the day of challenge. These results demonstrate that DNA vaccination in the absence of any heterologous boost can provide protection from high viremia comparable to any other vaccine modalities tested in this macaque model. AIDS ͉ DNA vaccine ͉ macaque animal model ͉ prophylactic vaccination

DNA and virus particle vaccination protects against acquisition and confers control of viremia upon heterologous simian immunodeficiency virus challenge

“…These recent data suggest that DNA-only vaccination can be very immunogenic in humans. In an effort to further optimize DNA vaccines, we and others have previously focused on the use of DNA-only immunization and have reported successful induction of protective immune responses against SIV (4)(5)(6)(7)(8). DNA vaccination provides advantages, including simplicity, stability, versatility, and repeated administration without immunity against an exogenous vector, together with induction of high levels of antigen-specific immune responses upon improved delivery by in vivo EP (reviewed in refs.…”

DNA Vaccines against Infectious Diseases and Cancer

“…IM-EP delivery of HIV-1 env DNA vaccines augmented Ag-specific cellular and humoral immune responses in mice and allowed a 10-fold reduction in vaccine dose, as compared to IM alone without EP (Liu et al, 2008). EP delivery of optimized plasmid DNAs encoding the majority of SIVmac239 proteins also elicited strong immune responses in rhesus macaques and decreased viremia in both the acute and chronic phases of infection following challenge with pathogenic SIVmac251 (Rosati et al, 2009). At the same time, our group also demonstrated the availability of skin + EP delivery using pig and macaque models, showing that high plasmid concentrations resulted in improved gene expression for plasmid green fluorescent protein delivered by the intradermal/subcutaneous route and higher cellular and humoral responses to an HIV DNA vaccine, suggesting that ID-EP may have importance as an immunization approach in larger animals (Hirao et al, 2008b).…”

“…For delivery of DNA vaccines, a variety of methods including intradermal, intramuscular (i.m. ), mucosal, biojector injections and EP have been reported (Fynan et al, 1993;Pertmer et al, 1995;Kuklin et al, 1997;Ray et al, 1997;Chen et al, 1998;Luckay et al, 2007;Rosati et al, 2009). To date, the majority of DNA vaccine studies have utilized skin or muscle as an immunization target.…”

“…It has been suggested that the main reason for this might be resulting from a lack of APCs at the DNA injection site in humans as there are very few professional APCs in muscles after DNA immunization (Barouch et al, 2002). However, EP, the administration of electrical pulses to muscle or dermal tissue following DNA injection, has been shown to enhance the immunogenicity of DNA vaccines in a wide variety of small and large animal models (Buchan et al, 2005;Folgori et al, 2006;Ahlén et al, 2007;Hooper et al, 2007;Luckay et al, 2007;Hirao et al, 2008b;Rosati et al, 2009). EP functions partially by increasing myocyte permeability and thus facilitating plasmid uptake and antigen expression by host cells (Aihara and Miyazaki, 1998;Rizzuto et al, 1999;Widera et al, 2000;Gronevik et al, 2005).…”

Protection Afforded by an HIV Vaccine Candidate in Macaques Depends on the Dose of SIVmac251at Challenge Exposure

“…Twenty macaques were immunized at 0 and 8 weeks with intramuscular injection of 2 ml (4 0.5-ml doses) of a DNA-SIVgpe mixture containing a total of 8 mg endotoxin-free SIV mac239 -derived optimized plasmid DNAs in phosphate-buffered saline (PBS): 206Sp57 gag (1 mg), 209S-MCP3-p39 (1 mg), 99S-SIV mac239 Env (2 mg), 103S-LAMP-pol (2 mg), and 147S-LAMP-NTV (2 mg) (12)(13)(14). All animals were boosted with ALVAC-SIVgpe at weeks 21, 40, and either 57 (6,100 TCID 50 group) or 61 (470 TCID 50 group) (Fig.…”