Enhanced in vivo immunogenicity of SIV vaccine candidates with cationic liposome-DNA complexes in a rhesus macaque pilot study

Fairman, Jeff; Moore, Joseph; Lemieux, Mathieu; Rompay, Koen Van; Geng, Yongzhi; Warner, John F.; Abel, Kristina

doi:10.4161/hv.5.3.6589

Cited by 25 publications

(17 citation statements)

References 56 publications

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“…Recently, CLDC was shown to effectively induce CD4 ϩ and CD8 ϩ T-cell responses against peptide and protein antigens in mice (44). Further, a CLDCadjuvanted simian immunodeficiency virus (SIV) vaccine induced stronger SIV-specific T-and B-cell responses than an SIV vaccine without adjuvant in rhesus macaques (14).…”

Section: Discussionmentioning

confidence: 99%

“…The plasmid DNA and liposome intermediates were each diluted with lactose in 1.4 mM Tris-HCl and then complexed under aseptic conditions to form the formulated drug substance. After reconstitution, the final drug product was a colloidal dispersion of 0.3 mg/ml DNA, 1.88 mg/ml DOTIM, and 1.05 mg/ml cholesterol at pH 7.0 containing 1.4 mM TrisHCl and 10% (wt/vol) lactose (14). The formulated drug substance was placed into vials and lyophilized to produce the drug product.…”

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confidence: 99%

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Potent Adjuvant Activity of Cationic Liposome-DNA Complexes for Genital Herpes Vaccines

Bernstein

Cardin

Bravo

et al. 2009

Clin Vaccine Immunol

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Development of a herpes simplex virus (HSV) vaccine is a priority because these infections are common. It appears that potent adjuvants will be required to augment the immune response to subunit HSV vaccines. Therefore, we evaluated cationic liposome-DNA complexes (CLDC) as an adjuvant in a mouse model of genital herpes. Using a whole-virus vaccine (HVAC), we showed that the addition of CLDC improved antibody responses compared to vaccine alone. Most important, CLDC increased survival, reduced symptoms, and decreased vaginal virus replication compared to vaccine alone or vaccine administered with monophosphoryl lipid A (MPL) plus trehalose dicorynomycolate (TDM) following intravaginal challenge of mice. When CLDC was added to an HSV gD2 vaccine, it increased the amount of gamma interferon that was produced from splenocytes stimulated with gD2 compared to the amount produced with gD2 alone or with MPL-alum. The addition of CLDC to the gD2 vaccine also improved the outcome following vaginal HSV type 2 challenge compared to vaccine alone and was equivalent to vaccination with an MPL-alum adjuvant. CLDC appears to be a potent adjuvant for HSV vaccines and should be evaluated further.Herpes simplex virus type 1 (HSV-1) and HSV-2 are two members of the HSV family of alphaherpesviruses, which establish lifelong latent infection in sensory neurons and lead to chronic herpes disease. HSV-1 infection causes facial/ocular disease, while HSV-2 is the leading cause of genital herpes, although both viruses can be found at oral and genital sites. Indeed, the incidence of HSV-1 genital disease is increasing and approximates that of HSV-2 in certain countries (17). Approximately 45 million people in the United States (20 to 30%) have genital herpes infection, and new infections occur at a rate of 1 million per year (17,29). One of the most serious complications of genital herpes occurs when the virus is transmitted from mother to neonate. Infection of the neonate causes significant morbidity and mortality, even with proper antiviral therapy (25). Genital herpes infection also increases the risk of acquiring human immunodeficiency virus (HIV) infection and increases shedding of HIV in genital lesions (5, 40).HSV-2 infection induces both humoral and T-cell-mediated immunity; however, the mechanisms that contribute to longterm control of genital herpes are not understood and could be different from those that will protect against primary infection or disease. Studies from animal models of HSV infection and human studies indicate that high levels of neutralizing antibodies, innate immunity natural killer (NK) cells, interferon (IFN), and macrophages contribute to protection from HSV infection, but the major determinants of HSV protection are both CD8 ϩ and especially CD4 ϩ T cells (7,9,23,27,30,31). Clearance of virus from recurrent lesions is also more closely correlated to T-cell immunity. Thus, when a recurrent lesion occurs, mononuclear cells, primarily CD4 ϩ T cells, infiltrate the lesion as early as 2 days after formation and ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Potent Adjuvant Activity of Cationic Liposome-DNA Complexes for Genital Herpes Vaccines

Bernstein

Cardin

Bravo

et al. 2009

Clin Vaccine Immunol

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“…The adjuvant activity of CLDC is mainly due to a stimulation of the innate immune system by nonmethylated CpG motifs within the plasmid which stimulate cells to produce IFNγ and IL-12 [28-29]. Because the CLDC adjuvant induces both strong B and T cell, including CD4 and CD8 T cell responses, we expected that a T cell response to the glycoproteins would enhance the protection provided by neutralizing antibody [28-32]. The addition of CLDC has recently been shown to increase both CD4 and CD8 T cell responses to an influenza vaccine and improved protection to drifted strains [33].…”

Section: Introductionmentioning

confidence: 99%

Effects of herpes simplex virus type 2 glycoprotein vaccines and CLDC adjuvant on genital herpes infection in the guinea pig

Bernstein

Earwood

Bravo

et al. 2011

Vaccine

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Genital herpes simplex virus (HSV) infections are common but results from vaccine trials with HSV-2 glycoprotein D (gD) have been disappointing. We therefore compared a similar HSV gD2 vaccine, to a further truncated gD2 vaccine, to a vaccine with gD2 plus gB2 and gH2/gL2 and to a vaccine with only gB2 and gH2/gL2 in a guinea pig model of genital herpes. All vaccines were administered with cationic liposome-DNA complexes (CLDC) as an adjuvant. All vaccines significantly decreased the severity of acute genital disease and vaginal virus replication compared to the placebo group. The majority of animals in all groups developed at least one episode of recurrent disease but the frequency of recurrent disease was significantly reduced by each vaccine compared to placebo. No vaccine was significantly more protective than gD2 alone for any of the parameters described above. No vaccine decreased recurrent virus shedding. When protection against acute infection of dorsal root ganglia and the spinal cord was evaluated all vaccines decreased the per cent of animal with detectable virus and the quantity of virus but again no vaccine was significantly more protective than another. Improvements in HSV-2 vaccines may require inclusion of more T cell targets, more potent adjuvants or live virus vaccines.

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“…23,48,49 Targeting dendritic cells (DC) that are essential for initiating immune responses, can be achieved by different nanomedicine size; N 100-nm nanomedicine target the peripheral immature DCs, and the smaller size~20-nm -50-nm nanomedicine drain to the lymph node resident DCs. 50 Modification of the surface of the nanomedicine with DCspecific receptor ligands has shown to increase the targeting specificity.…”

Section: Immunotherapeutic Nanomedicinesmentioning

confidence: 99%

Nanomedicine applications towards the cure of HIV

Lisziewicz¹,

Tőke²

2013

Nanomedicine: Nanotechnology, Biology and Medicine

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Enhanced in vivo immunogenicity of SIV vaccine candidates with cationic liposome-DNA complexes in a rhesus macaque pilot study

Cited by 25 publications

References 56 publications

Potent Adjuvant Activity of Cationic Liposome-DNA Complexes for Genital Herpes Vaccines

Potent Adjuvant Activity of Cationic Liposome-DNA Complexes for Genital Herpes Vaccines

Effects of herpes simplex virus type 2 glycoprotein vaccines and CLDC adjuvant on genital herpes infection in the guinea pig

Nanomedicine applications towards the cure of HIV

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