HSV amplicon-mediated Aβ vaccination in Tg2576 mice: differential antigen-specific immune responses

Bowers, William J.; Mastrangelo, Michael A.; Stanley, Hilary A.; Casey, Ann E.; Milo, Lawrence J.; Federoff, Howard J.

doi:10.1016/j.neurobiolaging.2004.04.006

Cited by 40 publications

(21 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the appealing characteristics of these vectors are their large insert capacity, favorable safety profile and broad cellular/tissue tropism -which extends to antigen presenting cells, such as dendritic cells (DC) [3]. As a result, helper-free HSV-1 amplicons encoding mammalian or microbial proteins can elicit strong, antigenspecific immune responses, and may have utility in a range of applications, including cancer treatment and prophylactic vaccination against pathogens such as human immunodeficiency virus type-1 (HIV-1) [3][4][5][6][7][8][9][10].…”

Section: Introductionmentioning

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

Self Cite

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

Section: Introductionmentioning

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…We previously showed that the HSV amplicon is an effective gene transfer and vaccine platform for the preclinical evaluation of therapeutic actions in many mouse models of neurological and oncologic diseases (Geschwind et al, 1996;Carew et al, 2001;Zager et al, 2001;Bennett et al, 2002;Bowers et al, 2002Bowers et al, , 2005Delman et al, 2002;Sortwell et al, 2007). These prior results led us to develop an immunotherapeutic approach by combining the HSV amplicon vaccine platform with the most potent antigen-presenting cells, dendritic cells.…”

Section: Discussionmentioning

confidence: 99%

Effects of Herpes Simplex Virus Amplicon Transduction on Murine Dendritic Cells

et al. 2009

Self Cite

View full text Add to dashboard Cite

The herpes simplex virus (HSV)-based amplicon is a versatile vaccine platform that has been preclinically vetted as a gene-based immunotherapeutic for cancer, HIV, and neurodegenerative disorders. Although it is well known that injection of dendritic cells (DCs) transduced ex vivo with helper virus-free HSV amplicon vectors expressing disease-relevant antigens induces antigen-specific immune responses, the cellular receptor(s) by which the amplicon virion gains entry into DCs, as well as the effects that viral vector transduction impinges on the physiological status of these cells, is less understood. Herein, we examine the effects of amplicon transduction on mouse bone marrow-derived DCs. We demonstrate that HSV-1 cellular receptors HveC and HveA are expressed on the cell surface of murine DCs, and that HSV amplicons transduce DCs at high efficiency (>90%) with minimal effects on cell viability. Transduction of dendritic cells with amplicons induces a transient DC maturation phenotype as represented by self-limited upregulation of MHCII and CD11c markers. Mature DCs are less sensitive to HSV amplicon transduction than immature DCs regarding DC-related surface marker maintenance. From this and our previous work, we conclude that HSV amplicons transduce DCs efficiently, but impart differential and transient physiological effects on mature and immature DC pools, which will facilitate fine-tuning of this vaccination platform and further exploit its potential in immunotherapy.

show abstract

“…Other therapeutic Ab vaccination strategies that are currently being pursued include immunoconjugates and monoclonal antibodies, although amplicon vectors derived from agents such as the herpes simplex virus 65 and direct genetic therapies have also been suggested as suitable methods for the treatment of AD. Moreover, it is possible that active and passive immunization approaches may be synergistic, and thereby could be used effectively in tandem.…”

Section: Discussionmentioning

confidence: 99%

Immunization in Alzheimer's disease: naïve hope or realistic clinical potential?

et al. 2008

View full text Add to dashboard Cite

There has been considerable recent interest in vaccination of patients by immunotherapy as a potentially clinically useful methodology for combating histopathological changes in Alzheimer's disease (AD). The focus of the majority of this research has been on (1) active immunotherapy using the pre-aggregated synthetic b-amyloid (Ab) 42 preparation AN1792 vaccine (QS-21), or (2) passive immunization using injections of already prepared polyclonal anti-Ab antibodies (intravenous immunoglobulin). These two clinical approaches to the treatment of patients with AD represent the focus of this review. We conclude here that, with certain caveats, immunization offers further potential as a technique for the treatment (and possible prevention) of AD. New studies are seeking to develop and apply safer vaccines that do not result in toxicity and neuroinflammation. Nevertheless, caution is warranted, and future clinical investigations are required to tackle key outstanding issues. These include the need to demonstrate efficacy in humans as well as animal models (especially with respect to the potentially toxic side effects of immunotherapy), and fine-tuning in safely guiding the immune response. The issue of defining necessary and sufficient criteria for determining clinical efficacy remains an additional important issue for future immunization trials. The vaccination methodology appears to offer substantial current promise for clearing both soluble and aggregated amyloid in AD. However, it remains to be determined whether this approach will help to repair already damaged neural systems in the disease, and the extent to which vaccination-driven amyloid clearance will impact beneficially on patients' neurocognitive capacity and their functional status. The outcomes of future studies will be important both clinically and scientifically: an important further test of the validity of the amyloid hypothesis of AD is to evaluate the impact of an effective anti-amyloid strategy on the functional status of patients with this disease.

show abstract

HSV amplicon-mediated Aβ vaccination in Tg2576 mice: differential antigen-specific immune responses

Cited by 40 publications

References 65 publications

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

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

Effects of Herpes Simplex Virus Amplicon Transduction on Murine Dendritic Cells

Immunization in Alzheimer's disease: naïve hope or realistic clinical potential?

Contact Info

Product

Resources

About