Definitive toxicology and biodistribution study of a polyvalent DNA prime/protein boost human immunodeficiency virus type 1 (HIV-1) vaccine in rabbits

Pal, Ranajit; Qiao, Yu; WANG, S; Kalyanaraman, Vaniambadi S.; Nair, Bindukumar; Hudacik, Lauren; Whitney, Stephen; Keen, T.E.B.; Hung, Chia-Ling; Hocker, Lindsey

doi:10.1016/j.vaccine.2005.07.112

Cited by 32 publications

(27 citation statements)

References 20 publications

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“…Multi-gene, polyvalent, DNA prime-protein boost formulation DP6−001 2.1.a. DNA vaccines-The DP6−001 vaccine contains equal amounts of six individual DNA plasmid components utilizing the same vector pSW3891 [17]: five plasmids each encoding a codon-optimized gp120 gene sequence from the following primary HIV-1 Envelope proteins: subtypes A (92UG037.8), B (92US715.6 and Bal), C (96ZM651) and E (93TH976.17) and the sixth plasmid encoding a codon-optimized gag gene from subtype C (96ZM651) as previously described [28]. The cGMP plasmid DNA for this Phase I clinical trial was produced by Althea Technology (San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

“…The recombinant Env protein vaccine components included in the DP6−001 formulation contain equal amounts of five gp120 proteins matching that used in DNA prime components and were produced in CHO cell lines by Advanced BioScience Laboratories (ABL, Kensington, MD) using GMP compliance as previously described [28]. The final protein vaccine product was supplied in saline and re-formulated at the time of injection with 50μg of QS-21 adjuvant (Antigenics Inc., Woburn, MA) and 30 mg of excipient cyclodextrin (Cargill Cerestar USA Inc., Hammond, IN), to reach a final concentration of 0.375 mg/ml of five gp120 proteins (0.075 mg/ml/each protein) [28].…”

Section: 1b Protein Vaccines-mentioning

confidence: 99%

“…The final protein vaccine product was supplied in saline and re-formulated at the time of injection with 50μg of QS-21 adjuvant (Antigenics Inc., Woburn, MA) and 30 mg of excipient cyclodextrin (Cargill Cerestar USA Inc., Hammond, IN), to reach a final concentration of 0.375 mg/ml of five gp120 proteins (0.075 mg/ml/each protein) [28].…”

Section: 1b Protein Vaccines-mentioning

confidence: 99%

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Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Wang

Kennedy

West

et al. 2008

Vaccine

124

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An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report the induction of Human Immunodeficiency Virus Type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime-protein boost HIV-1 vaccine formulation, DP6−001 in a Phase I clinical trial conducted in healthy adult volunteers of both genders. Robust cross-subtype HIV-1-specific T cell responses were detected in IFNγ ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 Env antigens and also neutralized pseudotyped viruses that express the primary Env antigens from multiple HIV-1 subtypes. These findings demonstrate that the DNA prime-protein boost approach is an effective immunization method to elicit both humoral and cellmediated immune responses in humans, and that a polyvalent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds.

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Section: Methodsmentioning

confidence: 99%

Section: 1b Protein Vaccines-mentioning

confidence: 99%

Section: 1b Protein Vaccines-mentioning

confidence: 99%

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Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Wang

Kennedy

West

et al. 2008

Vaccine

124

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“…A previous detailed report of exaggerated skin reactions following re-administration of gp160 in HIV+ subjects was attributed to contaminating insect cell proteins [20], and is not similar to our observations of DTH or vasculitis. Our rabbit toxicology study demonstrated gradual clearance of DNA plasmids over several months at skin and muscle sites of DNA inoculations [3], suggesting that some skin reactions observed may be attributable to prolonged presence of Env antigen at the DNA inoculation sites.…”

mentioning

confidence: 68%

“…Recently, we reported that a novel multi-gene, polyvalent DNA prime-recombinant protein boost HIV vaccine formulation, DP6-001, elicited strong and balanced humoral and cell-mediated immunity in healthy, HIV-1-negative adult subjects [1]. Preclinical testing of DP6-001 demonstrated no significant adverse reactions in either rabbits or non-human primates despite the induction of robust immunity [2,3]. Previously tested HIV DNA vaccines have demonstrated excellent human safety profiles [4][5][6][7][8][9].…”

Section: Hiv; Vaccine; Adverse Event; Vasculitismentioning

confidence: 99%

The safety and tolerability of an HIV-1 DNA prime–protein boost vaccine (DP6-001) in healthy adult volunteers

Kennedy

Green

et al. 2008

Vaccine

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This report describes the safety observations following administration of a polyvalent DNA primeprotein boost HIV-1 vaccine formulated with adjuvant QS21. Local injection site reactionswere the most common (65% of subjects), and included type IV delayed-type hypersensitivity (DTH) reactions at prior DNA inoculation sites in 12 of 28 (43%) subjects following protein vaccination. Systemic reactions revealed two cases of vasculitis temporally related to inoculation with recombinant Env protein + QS21 adjuvant. Questions remain regarding the cause of the vasculitis, but the unique DTH observation may have contributed to the high level of immune responses previously reported for this vaccine. Keywords HIV; vaccine; adverse event; vasculitisOver the past two decades, various HIV vaccines have been tested for safety and several for efficacy in humans. However, the majority have not reproduced, in humans, the high immunogenicity seen in preclinical testing. Recently, we reported that a novel multi-gene, polyvalent DNA prime-recombinant protein boost HIV vaccine formulation, DP6-001, elicited strong and balanced humoral and cell-mediated immunity in healthy, HIV-1-negative adult subjects [1]. Preclinical testing of DP6-001 demonstrated no significant adverse reactions in either rabbits or non-human primates despite the induction of robust immunity [2,3]. Previously tested HIV DNA vaccines have demonstrated excellent human safety profiles [4][5][6][7][8][9]. Recombinant protein-based HIV vaccines formulated with QS21 adjuvant have reported local reactions, but have shown limited systemic adverse events in humans [10][11][12][13][14][15]. The current report summarizes the phase 1 clinical safety and tolerability data, highlighting local and *Address correspondence to: Jeff Kennedy, M.D., Division of Molecular Medicine, Wadsworth Center, Biggs Laboratory, ESP, C606, NYS Department of Health, P.O. Box 509, Albany, New York 12201-0509, P: 518-473-8421, F: 518-473-2900, E: jsk07@health.state.ny.us. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The clinical trial was an open-label, 3-arm design requiring each subject to receive two vaccine components; three sequential inoculations using a DNA plasmid vaccine administered either intradermally (ID) or intramuscularly (IM) followed by two sequential inoculations using a protein vaccine as shown in Table 1. Healthy HIV-negative adults (aged 18-50) were enrolled under informed consent as previously described [1]. This study involved 2 dose levels of DNA vaccines (1.2mg (Groups A and B); 7.2mg (Group C)) expressing five gp120 Env ant...

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ADMEProcesses in Vaccines andPK/PDApproaches for Vaccination Optimization

Gómez-Mantilla

Trocóniz

Garrido

2015

Pharmaceutical Sciences Encyclopedia

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In order to present the current knowledge on vaccine absorption, distribution, metabolism, and excretion (ADME) and vaccine modeling, this chapter briefly summarizes how vaccines are developed, what type of vaccines are available, and how much it is known about their mechanisms of action. It also summarizes the current knowledge on the impact of administration routes, dosing schedules, and formulation on vaccine ADME processes, focusing on the vaccine properties that can be altered without modifying the antigens (Ag). The chapter then describes the influence of biopharmaceutics properties on vaccine pharmacokinetic (PK) processes such as absorption and distribution. Mathematical models may be used to optimize vaccination in cancer treatment. There is an urgent need to perform studies based on PK, pharmacodynamics, and systems biology principles, to get the longitudinal information required, that once analyzed under the model‐based framework, can be linked to the biopharmaceutical characteristics of the vaccine formulation.

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Definitive toxicology and biodistribution study of a polyvalent DNA prime/protein boost human immunodeficiency virus type 1 (HIV-1) vaccine in rabbits

Cited by 32 publications

References 20 publications

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

The safety and tolerability of an HIV-1 DNA prime–protein boost vaccine (DP6-001) in healthy adult volunteers

ADMEProcesses in Vaccines andPK/PDApproaches for Vaccination Optimization

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