A pilot phase II study of the safety and immunogenicity of HIV p17/p24:VLP (p24-VLP) in asymptomatic HIV seropositive subjects

Peters, Barry; Cheingsong-Popov, Rachanee; Callow, David; Foxall, Russell B.; Patou, Gary; Hodgkin, K; Weber, Jonathan

doi:10.1016/s0163-4453(97)92814-0

Cited by 46 publications

(22 citation statements)

References 21 publications

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“…RecgB expressed in muscle cells probably maintains a particle-like structure, as the purified recgB secreted by CHO cells (15), which probably favors its immunogenicity. Comparable results were previously reported for expressed antigens that spontaneously form particles (16) or for proteins or peptides expressed as viruslike particles (24,25,28). Analysis of antibody isotype in DNA-vaccinated mice revealed the presence of both IgGl and IgG2a, suggesting that the immune response developed after DNA immunization is Thland Th2-mediated.…”

Section: -supporting

confidence: 73%

Differential Neutralizing Antibody Responses to Varicella-Zoster Virus Glycoproteins B and E Following Naked DNA Immunization

Massaer¹,

Haumont²,

Garcia³

et al. 1999

Viral Immunology

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The only available vaccine against varicella-zoster virus (VZV) consists of the VZV-Oka attenuated but persistent virus strain. Development of a safer, subunit vaccine is therefore desirable. In this prospect, nucleic acid vaccines, expressing truncated forms of VZV glycoproteins B (recgB) and E (recgE) from which the anchor and the cytoplasmic domains were deleted, were used to immunize mice. Vaccination with recgB encoding plasmid elicited a strong and specific humoral immune response. Total IgG and neutralizing titres were comparable to those previously obtained by vaccination with purified and adjuvanted native recgB. In contrast, mice immunization with recgE encoding plasmid only induced a very weak immune response whereas we previously showed that vaccination with adjuvanted native or denatured recgE protein led to high neutralizing titres. The weakness of the immune response induced by recgE-encoding plasmid depended neither on the deletion of the anchor domain in the gE gene nor on the animal model. Analysis of antibody isotypes produced by plasmid immunizations revealed a response slightly dominated by IgG2a. Taken together, the data indicate that a VZV subunit vaccine based on adjuvanted recombinant glycoprotein E is more promising than a nucleic acid-based vaccine strategy. As regards recgB, both vaccination approaches might be appropriate.

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Section: -supporting

confidence: 73%

Differential Neutralizing Antibody Responses to Varicella-Zoster Virus Glycoproteins B and E Following Naked DNA Immunization

Massaer¹,

Haumont²,

Garcia³

et al. 1999

Viral Immunology

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“…Concordantly, specific increase of solely anti-p24 responses as achieved in vaccination with diverse p24 antigen regimens has not shown clinical benefits. [26][27][28][29][30][31][32][33][34][35] Hence, the boost in reactivites to p24 observed here likely reflects the capacity of the immune system to react to antigenic challenge and is not a direct correlate of protection. Previous studies on the prognostic value of antibodies to p24 measured absolute antibody levels at a specific time point and sought to derive associations with disease progression from these values.…”

Section: Discussionmentioning

confidence: 99%

Humoral immunity to HIV-1: kinetics of antibody responses in chronic infection reflects capacity of immune system to improve viral set point

Trkola¹

2004

Blood

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We analyzed the humoral immune response in 46 patients following structured treatment interruption (STI) to investigate the general potential of therapeutic vaccination in chronic HIV-1 infection. Evoked antibody titer increases to glycoprotein 120 (gp120) and p24 were low during 4 short-term STIs and only reached significance during a fifth long-term interruption. Although induction of binding antibodies to viral antigens was not associated with potent suppression of viremia, we observed that individuals with a rapid and high response to p24, and to a lesser extent also to gp120, lowered their viral set points significantly. Of note, the increase of the anti-p24 response correlated with specific CD4 T helper frequency to this antigen. Despite induction of binding antibody responses, which correlated with improved viral control, the increase in neutralizing activity was marginal and did not lead to this enhanced viral suppression. However, a subgroup of patients who potently suppressed viremia independently of STI had significantly higher pre-existing neutralization titers, suggesting a role of humoral immunity in conferring potent protection. In summary, measuring the kinetics of antibody responses provided a marker to validate the responsiveness and capacities of the immune system of HIV-1-infected individuals and reflected the patients' ability to decrease viral set points.

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“…An alternative HIV-1 VLP vaccine candidate has been produced in yeast as a chimeric non-enveloped VLP by fusing HIV-1 p17 and p24 proteins to p1 protein of S. cerevisiae retrotransposon Ty [129]. The resulting HIV-1 p17/p24:Ty chimeric VLPs elicited HIV-specific serum antibodies in rabbits [129] and were immunogenic when evaluated in prophylactic clinical studies [130,131], but were not effective as a therapeutic vaccine (Table 2) [132].…”

Section: Yeastmentioning

confidence: 99%

Virus-like particles as a highly efficient vaccine platform: Diversity of targets and production systems and advances in clinical development

Kushnir

Streatfield

Yusibov

2012

Vaccine

518

403

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Virus-like particles (VLPs) are a class of subunit vaccines that differentiate themselves from soluble recombinant antigens by stronger protective immunogenicity associated with the VLP structure. Like parental viruses, VLPs can be either non-enveloped or enveloped, and they can form following expression of one or several viral structural proteins in a recombinant heterologous system. Depending on the complexity of the VLP, it can be produced in either a prokaryotic or eukaryotic expression system using target-encoding recombinant vectors, or in some cases can be assembled in cell-free conditions. To date, a wide variety of VLP-based candidate vaccines targeting various viral, bacterial, parasitic and fungal pathogens, as well as non-infectious diseases, have been produced in different expression systems. Some VLPs have entered clinical development and a few have been licensed and commercialized. This article reviews VLP-based vaccines produced in different systems, their immunogenicity in animal models and their status in clinical development.

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A pilot phase II study of the safety and immunogenicity of HIV p17/p24:VLP (p24-VLP) in asymptomatic HIV seropositive subjects

Cited by 46 publications

References 21 publications

Differential Neutralizing Antibody Responses to Varicella-Zoster Virus Glycoproteins B and E Following Naked DNA Immunization

Differential Neutralizing Antibody Responses to Varicella-Zoster Virus Glycoproteins B and E Following Naked DNA Immunization

Humoral immunity to HIV-1: kinetics of antibody responses in chronic infection reflects capacity of immune system to improve viral set point

Virus-like particles as a highly efficient vaccine platform: Diversity of targets and production systems and advances in clinical development

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