Rational design of a plasmid DNA vaccine capable of eliciting cell-mediated immune responses to multiple HIV antigens in mice

Egan, Michael A.; Megati, Shakuntala; Roopchand, Vidia; Garcia-Hand, Dorys; Luckay, Amara; Chong, Siew-Yen; Rosati, Margherita; Sackitey, Solomon; Weiner, David B.; Felber, Barbara K.; Pavlakis, George N.; Israel, Zimra R.; Eldridge, John H.; Sidhu, Maninder K.

doi:10.1016/j.vaccine.2005.08.024

Cited by 33 publications

(27 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Based on our prior studies (38-44), we used DNA constructs encoding rhesus macaque IL-12 or the enzymatically active A1 domain of E. coli heat-labile enterotoxin (LTA1) as genetic adjuvants. Others and we have shown that IL-12 is an excellent adjuvant for the induction of Th1 responses (38)(39)(40)(41)(42)(43)(44) as well as for augmenting ADCC activity in situ (45)(46)(47). We have also shown that LTA1 and the related enzymatically active A1 domain of cholera toxin (CTA1) are potent genetic adjuvants capable of augmenting antibody responses in mice (48)(49)(50).…”

Section: Resultsmentioning

confidence: 94%

Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection

Fouts

Bagley

Prado

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

117

122

View full text Add to dashboard Cite

A guiding principle for HIV vaccine design has been that cellular and humoral immunity work together to provide the strongest degree of efficacy. However, three efficacy trials of Ad5-vectored HIV vaccines showed no protection. Transmission was increased in two of the trials, suggesting that this vaccine strategy elicited CD4+ T-cell responses that provide more targets for infection, attenuating protection or increasing transmission. The degree to which this problem extends to other HIV vaccine candidates is not known. Here, we show that a gp120-CD4 chimeric subunit protein vaccine (full-length single chain) elicits heterologous protection against simian-human immunodeficiency virus (SHIV) or simian immunodeficiency virus (SIV) acquisition in three independent rhesus macaque repeated low-dose rectal challenge studies with SHIV162P3 or SIVmac251. Protection against acquisition was observed with multiple formulations and challenges. In each study, protection correlated with antibody-dependent cellular cytotoxicity specific for CD4-induced epitopes, provided that the concurrent antivaccine T-cell responses were minimal. Protection was lost in instances when T-cell responses were high or when the requisite antibody titers had declined. Our studies suggest that balance between a protective antibody response and antigen-specific T-cell activation is the critical element to vaccine-mediated protection against HIV. Achieving and sustaining such a balance, while enhancing antibody durability, is the major challenge for HIV vaccine development, regardless of the immunogen or vaccine formulation.

show abstract

Section: Resultsmentioning

confidence: 94%

Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection

Fouts

Bagley

Prado

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

117

122

View full text Add to dashboard Cite

show abstract

“…Our experiments were focused principally on the comparative analysis of different promoter elements in the context of the HSV-1 amplicon vector system, since the optimization of transcriptional control sequences has been shown to substantially improve the immunogenicity of both DNA plasmid and adenovirally-vectored vaccines [20,23,32,35,36,[42][43][44][45]. In HIV-1 DNA vaccines, the use of the hybrid CMV-I transcriptional control element resulted in improved immunogenicity, compared to vectors that contained a simple CMV promoter without Intron A [23,42,43].…”

Section: Discussionmentioning

confidence: 99%

“…These hybrid promoters contained combinations of the CMV promoter/enhancer together with (i) its associated Intron A element (CMV-I) [21,22,[32][33][34], (ii) the regulatory R region from the long terminal repeat (LTR) of the human T-cell leukemia virus type 1 (CMV-R) [20], and (iii) the chicken β-actin promoter and the woodchuck hepatitis virus regulatory element (CAG) [19]. Each of these composite CMV-based promoters has been reported to mediate improved levels of gene expression and/or enhanced immune responses to encoded antigens, when compared to the basic CMV promoter [35,36]. The other transcriptional regulatory elements that were incorporated into our amplicon panel included two retroviral LTRs and the HSV-1 immediate early 4/5 promoter, which was used in our previous studies on the immunogenicity of HSV amplicon-vectored HIV-1 antigens [4].…”

Section: Effect Of Different Transcriptional Control Elements On In Vmentioning

confidence: 99%

Effect of promoter strength on protein expression and immunogenicity of an HSV-1 amplicon vector encoding HIV-1 Gag

Santos¹,

Duke²,

Rodríguez-Colón³

et al. 2007

Vaccine

View full text Add to dashboard Cite

Helper-free herpes simplex virus type-1 (HSV-1) amplicon vectors elicit robust immune responses to encoded proteins, including human immunodeficiency virus type-1 (HIV-1) antigens. To improve this vaccine delivery system, seven amplicon vectors were constructed, each encoding HIV-1 Gag under the control of a different promoter. Gag expression levels were analyzed in murine and human cell lines, as well as in biopsied tissue samples from injected mice; these data were then compared with Gag-specific T cell responses in BALB/c mice. The magnitude of the amplicon-induced immune response was found to correlate strongly with the level of Gag production both in vitro and in vivo. Interestingly, the best correlation of the strength of the amplicon-induced immune response was with antigen expression in cultured DC rather than expression at the tissue site of injection or in cultured cell lines. These findings may have implications for the generation of improved HSV-1 amplicon vectors for HIV-1 vaccine delivery.

show abstract

“…Although multiple antigens are commonly needed, the cloning of many genes into a single construct can become complicated. 3 Evidence suggests that a broad immune response composed of multiple antigens is more protective than a narrow focused response. 4,5 Since a single protective antigen has not been identified for many diseases, a strategy of delivering multiple antigens would, therefore, have an enhanced likelihood of success by increasing the number of potential antigens.…”

Section: Introductionmentioning

confidence: 99%

Multi-antigenic DNA immunization using herpes simplex virus type 2 genomic fragments

Braun¹,

Dong²,

Jerome³

et al. 2008

Human Vaccines

View full text Add to dashboard Cite

A novel DNA vaccine was generated using genomic fragments of a pathogen as the source of both the antigen coding and regulatory regions. The constructs, termed subgenomic vaccines (SGVs), incorporated genomic DNA sequences up to 45 kbp that encompass 15-20 different genes. The SGVs were developed to generate vaccines capable of expressing multiple genes from a single construct, which could be of great benefit for commercialization. The unique feature of the SGVs is that genes are expressed from their native promoters rather than heterologous promoters typical of DNA vaccines. SGVs composed of genomic fragments from the DS-DNA virus Herpes Simplex Virus Type 2 (HSV-2) induced HSV-2 specific immune responses following particle-mediated epidermal delivery (PMED) in mice and these responses protected animals from lethal infectious challenge. A second generation SGV (SGV-H2), intended as an HSV-2 therapeutic vaccine, was generated that had five HSV-2 genes and was capable of generating multi-antigenic responses in naïve mice, and enhancing responses in infected animals. When compared with standard single plasmid vaccines, immunization with the SGV-H2 was found to be at least as effective as single plasmids or plasmid mixtures. The activity of the SGV-H2 could be greatly enhanced by co-delivering plasmids expressing E. coli heat labile toxin (LT) or cholera toxin CT as adjuvants as has been found previously for standard single-gene DNA vaccines.

show abstract

Rational design of a plasmid DNA vaccine capable of eliciting cell-mediated immune responses to multiple HIV antigens in mice

Cited by 33 publications

References 38 publications

Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection

Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection

Effect of promoter strength on protein expression and immunogenicity of an HSV-1 amplicon vector encoding HIV-1 Gag

Multi-antigenic DNA immunization using herpes simplex virus type 2 genomic fragments

Contact Info

Product

Resources

About