Initial Studies on Active Immunization of HIV-Infected Subjects Using a gp120-Depleted HIV-1 Immunogen: Long-Term Follow-Up

Levine, Alexandra M.; Groshen, Susan; Allen, J. R.; Munson, Katharine M.; Carlo, Dennis J.; Daigle, Anne E.; Ferre, Francois; Jensen, Fred C.; Richieri, Steven P.; Trauger, Richard; Parker, Jōhn W.; Salk, Peter L.; Salk, Jonas

doi:10.1097/00042560-199604010-00005

Cited by 50 publications

(22 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results presented in this report confirmed the results of previous studies with the HIV-1 immunogen in terms of its ability to augment CD4-cell numbers and HIV-1-specific immune function in asymptomatic subjects not taking antiviral drug therapy (19,38,39). Furthermore, the augmentation of absolute CD4-cell numbers observed in this study is in contrast to the lack of beneficial effects observed with gp160 or gp120 therapeutic vaccines (11,14,34).…”

Section: Discussionsupporting

confidence: 89%

A Double-Blind, Adjuvant-Controlled Trial of Human Immunodeficiency Virus Type 1 (HIV-1) Immunogen (Remune) Monotherapy in Asymptomatic, HIV-1-Infected Thai Subjects with CD4-Cell Counts of >300

Churdboonchart¹,

Sakondhavat

Kulpradist

et al. 2000

Clin Diagn Lab Immunol

View full text Add to dashboard Cite

We examined the effect of a human immunodeficiency virus (HIV)-specific immune-based therapy in Thailand, where access to antiviral drug therapy is limited. A 40-week trial was conducted with 297 asymptomatic, HIV-infected Thai subjects with CD4-cell counts greater than 300 l/mm 3 . Subjects were randomized to receive either HIV type 1 (HIV-1) immunogen (Remune; inactivated HIV-1 from which gp120 is depleted in incomplete Freund's adjuvant or adjuvant control at 0, 12, 24, and 36 weeks at five different clinical sites in Thailand. Neither group received antiviral drug therapy. The a priori primary endpoint for the trial was changes in CD4-cell counts with secondary parameters of percent changes in CD8-cell counts (percent CD4, CD8, and CD4/CD8) and body weight. Subsets of subjects were also examined for changes in plasma HIV-1 RNA levels, Western blot immunoreactivity, and HIV-1 delayed-type hypersensitivity (DTH) skin test reactivity. There was a significant difference in changes in CD4-cell counts that favored the HIV-1 immunogen-treated group compared to those for the adjuvant-treated control group (P < 0.05). On average, for HIV-1 immunogentreated subjects CD4-cell counts increased by 84 cells by week 40, whereas the increase for the control group was 38 cells by week 40. This increase in CD4-cell count was associated with increased HIV-specific immunogenicity, as shown by Western blotting and enhanced HIV-1 DTH skin reactivity. No significant differences in adverse events were observed between the groups. The results of this trial suggest that HIV-1 immunogen is safe and significantly increases CD4-cell counts and HIV-specific immunity compared to those achieved with the adjuvant control in asymptomatic HIV-1-infected subjects not taking antiviral drugs.

show abstract

Section: Discussionsupporting

confidence: 89%

A Double-Blind, Adjuvant-Controlled Trial of Human Immunodeficiency Virus Type 1 (HIV-1) Immunogen (Remune) Monotherapy in Asymptomatic, HIV-1-Infected Thai Subjects with CD4-Cell Counts of >300

Churdboonchart¹,

Sakondhavat

Kulpradist

et al. 2000

Clin Diagn Lab Immunol

View full text Add to dashboard Cite

show abstract

“…Further problems associated with such treatments include toxicity and side effects, high cost, development of viral resistance, and low efficacy owing to viral genotype specificity/ patient variables (11,43,61,101,108,121,145,157,171). Efforts to develop conventional vaccines for HIV have been hampered by potential pathogenicity and poor capacity to elicit protective immune responses (6,54,80,162). Several new vaccination approaches for HIV (e.g., DNA and viral vectors) are in clinical trials (3,4,7,23,82,105,133,146).…”

Section: Tetraspanins As Potential Therapeutic Targets For Viruses Thmentioning

confidence: 99%

Tetraspanins in Viral Infections: a Fundamental Role in Viral Biology?

Martin

Roth

Jans

et al. 2005

J Virol

View full text Add to dashboard Cite

4The tetraspanins are a broadly expressed superfamily of transmembrane glycoproteins with over 30 members found in humans and with homologues conserved through distantly related species, including insects, sponges, and fungi. Members of this family appear to form large integrated signaling complexes or tetraspanin-enriched microdomains (TEMs) by their association with a variety of transmembrane and intracellular signaling/cytoskeletal proteins (49). These interactions link tetraspanins to an array of physiological functions and, in consequence, to numerous endogenous pathologies, including cancer development and inherited disorders (Table 1).Tetraspanins are also known to have roles in the pathology of infectious diseases such as diphtheria, malaria, and numerous viral infections (Table 1). The literature currently indicates that specific tetraspanin family members are selectively associated with specific viruses and affect multiple stages of infectivity, from initial cellular attachment to syncytium formation and viral particle release. Thus, the relationship of tetraspanins with viruses appears to be particularly complex.Here, we will consider this data in the context of recent developments in tetraspanin biology, particularly in our understanding of the architecture and function of TEMs. With the benefit of recent insights into tetraspanin function in cell fusion events and intracellular trafficking, we discuss common features of tetraspanin/viral associations which indicate a fundamental role for TEMs in a number of viral infections. We will also consider the existing therapeutic strategies for human immunodeficiency virus (HIV), hepatitis C virus (HCV), and human T-cell lymphotropic virus type 1 (HTLV-1), focusing on the potential therapeutic value of targeting TEMs, using peptide reagents based on tetraspanin extracellular regions.

show abstract

“…The different sites used for the sequential DNA priming, as well as two sequential protein boost inoculations, enabled the clinical separation of DTH-like reactions from local reactions induced by QS21 as reported in a previous HIV Env-QS21 vaccine study [10]. DTH reactions have been reported in other vaccine studies involving prophylactic vaccines against HIV [16], syphilis [17] and malaria [18], and a therapeutic vaccine for HIV [19]. 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.…”

mentioning

confidence: 91%

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

View full text Add to dashboard Cite

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...

show abstract

Initial Studies on Active Immunization of HIV-Infected Subjects Using a gp120-Depleted HIV-1 Immunogen: Long-Term Follow-Up

Cited by 50 publications

References 22 publications

A Double-Blind, Adjuvant-Controlled Trial of Human Immunodeficiency Virus Type 1 (HIV-1) Immunogen (Remune) Monotherapy in Asymptomatic, HIV-1-Infected Thai Subjects with CD4-Cell Counts of >300

A Double-Blind, Adjuvant-Controlled Trial of Human Immunodeficiency Virus Type 1 (HIV-1) Immunogen (Remune) Monotherapy in Asymptomatic, HIV-1-Infected Thai Subjects with CD4-Cell Counts of >300

Tetraspanins in Viral Infections: a Fundamental Role in Viral Biology?

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

Contact Info

Product

Resources

About