The potential of immunostimulatory CpG DNA for inducing immunity against genital herpes: opportunities and challenges

Harandi, Ali M.

doi:10.1016/j.jcv.2004.03.001

Cited by 20 publications

(13 citation statements)

References 22 publications

(19 reference statements)

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“…These synthetic molecules are considered as the most potent immunostimulating agent known to date. They were found to promote immune response against antigens, thanks to the stimulation of dendritic cells (13,14,16,211,212). The strategy based on therapeutic vaccine does not interfere with the viral cycle and should be insensitive to the emergence of multidrug-resistant strains as well.…”

Section: Treatments Against Infectionsmentioning

confidence: 99%

“…The strategy based on therapeutic vaccine does not interfere with the viral cycle and should be insensitive to the emergence of multidrug-resistant strains as well. Moreover, it should be very effective against the high immunogenic variability observed with certain viruses (211,213). So far, antisense strategies are the treatment of choice in the battle against HIV, cytomegalovirus, hepatitis C, and respiratory syncytial virus, however immunostimulating approaches have recently been receiving much attention as treatment for HIV, herpes virus, and influenza virus.…”

Section: Treatments Against Infectionsmentioning

confidence: 99%

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Nanotechnology: Intelligent Design to Treat Complex Disease

2006

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The purpose of this expert review is to discuss the impact of nanotechnology in the treatment of the major health threats including cancer, infections, metabolic diseases, autoimmune diseases, and inflammations. Indeed, during the past 30 years, the explosive growth of nanotechnology has burst into challenging innovations in pharmacology, the main input being the ability to perform temporal and spatial site-specific delivery. This has led to some marketed compounds through the last decade. Although the introduction of nanotechnology obviously permitted to step over numerous milestones toward the development of the "magic bullet" proposed a century ago by the immunologist Paul Ehrlich, there are, however, unresolved delivery problems to be still addressed. These scientific and technological locks are discussed along this review together with an analysis of the current situation concerning the industrial development.

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Section: Treatments Against Infectionsmentioning

confidence: 99%

Section: Treatments Against Infectionsmentioning

confidence: 99%

Nanotechnology: Intelligent Design to Treat Complex Disease

2006

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“…In mice, gC1 is a virulence factor based on its ability to bind C3b (21). HSV gE1 and gE2 function as IgG Fc receptors (22,23). We reported previously that gE1 inhibits activities mediated by the IgG Fc domain by a process described as antibody bipolar bridging (24).…”

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confidence: 99%

Blocking Herpes Simplex Virus 2 Glycoprotein E Immune Evasion as an Approach To Enhance Efficacy of a Trivalent Subunit Antigen Vaccine for Genital Herpes

Awasthi

Huang

Shaw

et al. 2014

J Virol

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Herpes simplex virus 2 (HSV-2) subunit antigen vaccines targeting virus entry molecules have failed to prevent genital herpes in human trials. Our approach is to include a virus entry molecule and add antigens that block HSV-2 immune evasion. HSV-2 glycoprotein C (gC2) is an immune evasion molecule that inhibits complement. We previously reported that adding gC2 to gD2 improved vaccine efficacy compared to the efficacy of either antigen alone in mice and guinea pigs. Here we demonstrate that HSV-2 glycoprotein E (gE2) functions as an immune evasion molecule by binding the IgG Fc domain. HSV-2 gE2 is synergistic with gC2 in protecting the virus from antibody and complement neutralization. Antibodies produced by immunization with gE2 blocked gE2-mediated IgG Fc binding and cell-to-cell spread. Mice immunized with gE2 were only partially protected against HSV-2 vaginal challenge in mice; however, when gE2 was added to gC2/gD2 to form a trivalent vaccine, neutralizing antibody titers with and without complement were significantly higher than those produced by gD2 alone. Importantly, the trivalent vaccine protected the dorsal root ganglia (DRG) of 32/33 (97%) mice between days 2 and 7 postchallenge, compared with 27/33 (82%) in the gD2 group. The HSV-2 DNA copy number was significantly lower in mice immunized with the trivalent vaccine than in those immunized with gD2 alone. The extent of DRG protection using the trivalent vaccine was better than what we previously reported for gC2/gD2 immunization. Therefore, gE2 is a candidate antigen for inclusion in a multivalent subunit vaccine that attempts to block HSV-2 immune evasion. IMPORTANCEHerpes simplex virus is the most common cause of genital ulcer disease worldwide. Infection results in emotional distress for infected individuals and their partners, is life threatening for infants exposed to herpes during childbirth, and greatly increases the risk of individuals acquiring and transmitting HIV infection. A vaccine that prevents genital herpes infection will have major public health benefits. Our vaccine approach includes strategies to prevent the virus from evading immune attack. Mice were immunized with a trivalent vaccine containing an antigen that induces antibodies to block virus entry and two antigens that induce antibodies that block immune evasion from antibody and complement. Immunized mice demonstrated no genital disease, and 32/33 (97%) animals had no evidence of infection of dorsal root ganglia, suggesting that the vaccine may prevent the establishment of latency and recurrent infections. T he efficacy of the herpes simplex virus 2 (HSV-2) glycoprotein D (gD2) subunit antigen vaccine for prevention of genital herpes was evaluated in three large human trials (1, 2). In 2002, the first two trials reported that the gD2 vaccine prevented HSV-2 genital disease in HSV-1/HSV-2-seronegative women; however, this result was not reproduced in the 2012 Herpevac trial for women that showed gD2 vaccine efficacy in preventing genital disease caused by HSV-1 but n...

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“…Initial in vivo mouse studies revealed that administration of CpG oligodeoxynucleotide (CpG-ODN) alone by vaginal, rectal, or gastrointestinal routes provided nonspecific protection against genital herpes, via stimulation of local production of macrophage-inflammatory protein-1␣ (MIP-1␣), MIP-1␤, regulated on activation, normal T expressed and secreted, and IFNinducible protein 10, as well as of IL-12 and IL-18 [35,36]. It is remarkable that mucosal administration of CpG coupled to CT-B (CTB-CpG) increased the local production of these factors, even across the species specificity of CpG oligonucleotides and could drive a Th1-biased, humoral response against coadministered tetanus toxoid.…”

Section: Novel Routes and Adjuvants For Mucosal Vaccinesmentioning

confidence: 99%