Prime-Boost Vaccination with HIV-1 Gag Protein and Cytosine Phosphate Guanosine Oligodeoxynucleotide, Followed by Adenovirus, Induces Sustained and Robust Humoral and Cellular Immune Responses

Tritel, Marc; Stoddard, Amy; Flynn, Barbara J.; Darrah, Patricia A.; Wu, Cheng-Hung; Wille, Ulrike; Shah, Javeed A.; Huang, Yue; Xu, Li; Betts, Michael R.; Nabel, Gary J.; Seder, Robert A.

doi:10.4049/jimmunol.171.5.2538

Cited by 70 publications

(51 citation statements)

References 66 publications

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“…They used DNA encoding a chimeric protein of HIV-1 Gag and lysosomal associated membrane protein-1. When BALB/c mice were primed with both plasmid DNA encoding HIV-1 Gag and CpG followed by adenovirus boost, robust humoral and cellular immune responses were elicited [51]. A DNA primeadenovirus boost regimen against domain four of Bacillus anthracis protective antigen induced both humoral and cellular immune responses in A/J mice [52].…”

Section: Discussionmentioning

confidence: 99%

Enhancing Th2 immune responses against amyloid protein by a DNA prime-adenovirus boost regimen for Alzheimer's disease

et al. 2007

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Accumulation of aggregated amyloid β-protein (Aβ) in the brain is thought to be the initiating event leading to neurodegenetation and dementia in Alzheimer's disease (AD). Therefore, therapeutic strategies that clear accumulated Aβ and/or prevent Aβ production and its aggregation are predicted to be effective against AD. Immunization of AD mouse models with synthetic Aβ prevented or reduced Aβ load in the brain and ameliorated their memory and learning deficits. The clinical trials of Aβ immunization elicited immune responses in only 20% of AD patients and caused T-lymphocyte meningoencephalitis in 6% of AD patients. In attempting to develop safer vaccines, we previously demonstrated that an adenovirus vector, AdPEDI-(Aβ1-6) 11 , which encodes 11 tandem repeats of Aβ1-6 can induce anti-inflammatory Th2 immune responses in mice. Here, we investigated whether a DNA prime-adenovirus boost regimen could elicit a more robust Th2 response using AdPEDI-(Aβ1-6) 11 and a DNA plasmid encoding the same antigen. All mice (n = 7) subjected to the DNA prime-adenovirus boost regimen were positive for anti-Aβ antibody, while, out of 7 mice immunized with only AdPEDI-(Aβ1-6) 11 , four mice developed anti-Aβ antibody. Anti-Aβ titers were indiscernible in mice (n = 7) vaccinated with only DNA plasmid. The mean anti-Aβ titer induced by the DNA prime-adenovirus boost regimen was approximately 7-fold greater than that by AdPEDI-(Aβ1-6) 11 alone. Furthermore, anti-Aβ antibodies induced by the DNA prime-adenovirus boost regimen were predominantly of the IgG1 isotype. These results indicate that the DNA primeadenovirus boost regimen can enhance Th2-biased responses with AdPEDI-(Aβ1-6) 11 in mice and suggest that heterologous prime-boost strategies may make AD immunotherapy more effective in reducing accumulated Aβ.

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Section: Discussionmentioning

confidence: 99%

Enhancing Th2 immune responses against amyloid protein by a DNA prime-adenovirus boost regimen for Alzheimer's disease

et al. 2007

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“…Replication-defective Ad (by virture of an E1 deletion) offer some of the same attractive features as replicating Ad vectors, including infection of dendritic cells and cells lining mucosal inductive sites [11,59,115]. Likewise, they do not integrate into the host DNA, can be easily scaled up, and stably express gene inserts.…”

Section: Replication Defective Vectorsmentioning

confidence: 99%

Replicating adenovirus vector prime/protein boost strategies for HIV vaccine development

Patterson

Robert-Guroff

2008

Expert Opinion on Biological Therapy

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Background-In the last few years the HIV vaccine field has moved forward a number of promising vaccine candidates into human clinical trials.Objective-In this review we briefly discuss the advances made in vaccine development and HIV pathogenesis and give an overview of the body of work our lab has generated in multiple animal models on replication-competent Ad recombinant vaccines.Methods-Emphasis is placed on comparative examination of vaccine components, routes of immunization and challenge models using replicating Ad vectors.Results/conclusion-The overall findings make the case that replicating Ad vectors are superior in priming multiple arms of the immune system, and in conjunction with protein boosting, have resulted in dramatic protective efficacy leading to their advancement to phase 1 trials. Implications of the recent halting of the Merck Ad5-HIV phase 2b clinical trial for our vaccine approach and other vectored vaccines are discussed.

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“…Purified PBMCs were thawed, resuspended, and stimulated as previously described (6). Anti-CD107a FITC (BD Biosciences) was added at the start of all stimulation periods, as described previously (23) …”

Section: Multifunctional Assessment Of Siv-specific T Cell Responsesmentioning

confidence: 99%

Vaccine-Induced, Simian Immunodeficiency Virus-Specific CD8+ T Cells Reduce Virus Replication but Do Not Protect from Simian Immunodeficiency Virus Disease Progression

Engram

Dunham

Makedonas

et al. 2009

The Journal of Immunology

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Our limited understanding of the interaction between primate lentiviruses and the host immune system complicates the design of an effective HIV/AIDS vaccine. To identify immunological correlates of protection from SIV disease progression, we immunized two groups of five rhesus macaques (RMs) with either modified vaccinia Ankara (MVA) or MVAΔudg vectors that expressed SIVmac239 Gag and Tat. Both vectors raised a SIV-specific CD8+ T cell response, with a magnitude that was greater in mucosal tissues than in peripheral blood. After challenge with SIVmac239, all vaccinated RMs showed mucosal and systemic CD8+ T cell recall responses that appeared faster and were of greater magnitude than those in five unvaccinated control animals. All vaccinated RMs showed a ∼1-log lower peak and early set-point SIV viral load than the unvaccinated animals, and then, by 8 wk postchallenge, exhibited levels of viremia similar to the controls. We observed a significant direct correlation between the magnitude of postchallenge SIV-specific CD8+ T cell responses and SIV viral load. However, vaccinated RMs showed no protection from either systemic or mucosal CD4+ T cell depletion and no improved survival. The observation that vaccine-induced, SIV-specific CD8+ T cells that partially control SIVmac239 virus replication fail to protect from immunological or clinical progression of SIV infection underscores both the complexity of AIDS pathogenesis and the challenges of properly assessing the efficacy of candidate AIDS vaccines.

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Prime-Boost Vaccination with HIV-1 Gag Protein and Cytosine Phosphate Guanosine Oligodeoxynucleotide, Followed by Adenovirus, Induces Sustained and Robust Humoral and Cellular Immune Responses

Cited by 70 publications

References 66 publications

Enhancing Th2 immune responses against amyloid protein by a DNA prime-adenovirus boost regimen for Alzheimer's disease

Enhancing Th2 immune responses against amyloid protein by a DNA prime-adenovirus boost regimen for Alzheimer's disease

Replicating adenovirus vector prime/protein boost strategies for HIV vaccine development

Vaccine-Induced, Simian Immunodeficiency Virus-Specific CD8+ T Cells Reduce Virus Replication but Do Not Protect from Simian Immunodeficiency Virus Disease Progression

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