Induction of neutralizing antibodies and cytotoxic T lymphocytes in Balb/c mice immunized with virus-like particles presenting a gp120 molecule from a HIV-1 isolate of clade A

Buonaguro, Luigi; Means, Anthony; Tornesello, Maria Lina; Arra, Claudio; Visciano, Maria Luisa; Biryahwaho, Benon; Sempala, S. D. K.; Giraldo, Gaetano; Buonaguro, Franco M.

doi:10.1016/s0166-3542(02)00004-9

Cited by 68 publications

(48 citation statements)

References 53 publications

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“…We can also exclude that successful vaccination of mice using H⌬gp2-syngag-1 was caused by a mere adjuvant effect of the vector, because only minute amounts of p24 of maximally 6 ng were present in the inocula, which is approximately 1,000-fold below the p24 amounts that have been used for successful vaccination using HIV Gag virus-like particles. As such, a specific anti-HIV CTL response to protein in the used inocula is highly unlikely (6,7).…”

Section: Discussionmentioning

confidence: 99%

Potential of Equine Herpesvirus 1 as a Vector for Immunization

Trapp

Einem

Hofmann

et al. 2005

J Virol

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Key problems using viral vectors for vaccination and gene therapy are antivector immunity, low transduction efficiencies, acute toxicity, and limited capacity to package foreign genetic information. It could be demonstrated that animal and human cells were efficiently transduced with equine herpesvirus 1 (EHV-1) reconstituted from viral DNA maintained and manipulated in Escherichia coli. Between 13 and 23% of primary human CD3 ؉ , CD4 ؉ , CD8 ؉ , CD11b ؉ , and CD19 ؉ cells and more than 70% of CD4 ؉ MT4 cells or various human tumor cell lines (MeWo, Huh7, HeLa, 293T, or H1299) could be transduced with one infectious unit of EHV-1 per cell. After intranasal instillation of EHV-1 into mice, efficient transgene expression in lungs was detectable. Successful immunization using EHV-1 was shown after delivery of the human immunodeficiency virus type 1 Pr55 gag precursor by the induction of a Gag-specific CD8 ؉ immune response in mice. Because EHV-1 was not neutralized by human sera containing high titers of antibodies directed against human herpesviruses 1 to 5, it is concluded that this animal herpesvirus has enormous potential as a vaccine vector, because it is able to efficiently transduce a variety of animal and human cells, has high DNA packaging capacity, and can conveniently be maintained and manipulated in prokaryotic cells.Equine herpesvirus 1 (EHV-1), an alphaherpesvirus, causes infections in equines. Usually the disease induced by the virus is mild, and approximately 90% of equines worldwide harbor the agent, whose persistence in animals is lifelong. One of the peculiarities of EHV-1 is its tropism for blood mononuclear cells, which are the primary site for establishment of EHV-1 latency. Neuronal tissues, including the trigeminal ganglion and the brain, are only rarely infected by the agent. Neurological symptoms after infection of equines with certain EHV-1 strains are caused by infection of endothelial cells and subsequent hypoxia and neuronal degradation and are consistent with myeloencephalopathy and not myeloencephalitis (40,62).Herpesviridae enter target cells by fusion of the viral envelope with the plasma membrane at neutral pH after attachment of virions to cell surface glycosaminoglycans (47,51). Glycoproteins are crucially involved in these early stages of infection, and 11 glycoproteins in the prototype member of the Alphaherpesvirinae subfamily, Herpes simplex virus type 1 (HSV-1), have been identified. The herpesvirus glycoproteins involved in attachment, receptor binding, and fusion (i.e., gB, gC, gD, and the gH-gL complex) also appear to largely determine the mostly very restricted host tropism of Alphaherpesvirinae, i.e., the inability of animal viruses to naturally infect species other than those they have coevolved with (23). While the first contact and heparin-sensitive attachment of the studied alphaherpesviruses, including EHV-1, is mainly mediated by gC, receptor binding of HSV-1, pseudorabies virus, and bovine herpesvirus 1 (BHV-1) is via interaction of gD with cellular receptors th...

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Section: Discussionmentioning

confidence: 99%

Potential of Equine Herpesvirus 1 as a Vector for Immunization

Trapp

Einem

Hofmann

et al. 2005

J Virol

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“…The HIV-targeted VLPs (HIVVLPs) are based on the HIV-1 Pr55gag precursor protein property to assemble as immature, non-replicating and non-infectious VLPs with an effective induction of both arms of the immune response [7][8][9][10][11][12][13]. In particular, the enveloped HIV-VLPs developed in our laboratory present an entire gp120 molecule derived from an Ugandan HIV-1 isolate of the clade A, identified in our laboratory [11;14;15].…”

Section: Introductionmentioning

confidence: 99%

“…In particular, the enveloped HIV-VLPs developed in our laboratory present an entire gp120 molecule derived from an Ugandan HIV-1 isolate of the clade A, identified in our laboratory [11;14;15]. The HIV-VLP A s show a strong in vivo immunogenicity in Balb/c mice, in absence of adjuvants, and HIV-1-specific CTLs as well as cross-clade neutralizing antibodies, active on primary HIV-1 isolates, have been detected in immunized animals [12]. Furthermore, the immunogenicity of the HIV-VLP A s has been evaluated in Balb/c mice by intra-nasal (i.n.)…”

Section: Introductionmentioning

confidence: 99%

DNA–VLP prime–boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity

Buonaguro

Devito

Tornesello

et al. 2007

Vaccine

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The immune response to HIV-1 Virus-Like Particles (VLPs), presenting a clade A Ugandan gp120, has been evaluated in a mouse model by intranasal (i.n.) administration by a VLP+VLP homologous or a DNA+VLP heterologous prime-boost immunization protocol, including a HIV-1 DNA gp160/rev plasmid. Furthermore, the effect of the Eurocine lipidbased mucosal L3 adjuvant on the VLP immunogenicity has been assessed as well.The designed heterologous protocol is able to increase the env-specific humoral and cellular immune response, compared to the homologous protocol, which is to some extent increased by the administration of L3-adjuvanted VLP boosting dose. The anti-gag response is statistically increased in both homologous and heterologous protocols, particularly when the VLP boosting dose is adjuvanted.Immune sera from immunized animals exhibit >50% ex vivo neutralizing activity against heterologous A and B-clade viral isolates. An envelope B-cell epitope mapping shows an enhanced response against V3 epitopes all across the C2-V5 region in the heterologous prime-boost immunization strategy.The induction of humoral immunity at mucosal sites, which represents the main port of entry for the HIV-1 infection, is extremely relevant. In this framework, the DNA-VLP heterologous prime-boost protocol appears a promising preventive vaccine approach which can significantly benefit from specific mucosal adjuvants, as the Eurocine L3.

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“…Foreign proteins are imbedded into VLP envelopes during budding and are displayed on the surface of the VLPs. HIV-VLPs displaying Env glycoprotein (gp120) have been produced in insect cells and induce humoral and cellular immune responses [15,16]. HIV-1-specific CTLs and cross-clade neutralizing antibodies have been detected in immunized mice.…”

Section: Virus-like Particles Vlps As Vaccinesmentioning

confidence: 99%

“…One enveloped virus protein, human immunodeficiency virus (HIV) type 1 gag protein, cannot assemble efficiently in yeast but in spheroplasts [46] and the formation of HIV type 2 virus gag protein VLPs has also failed in yeast [47]. However, in insect cells, HIV 1 gag protein VLPs can be formed and secreted into culture medium efficiently using baculovirus expression systems [15,16] and stably transformed cell systems [48]. Another enveloped virus protein, influenza A virus matrix protein (M1), can be assembled in insect cells and its VLPs are produced rapidly and easily in sufficient amounts [49] using Spodopterafrugiperda 9 (Sf-9) and High Five cells.…”

Section: Insectsmentioning

confidence: 99%

Functional Virus-Like Particles Production Using Silkworm and Their Application in Life Science

Kato¹,

Deo²,

Park

et al. 2012

J Biotechnol Biomaterial

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Virus-like particles (VLPs), which mimic the structure of authentic virus, are of significant importance owing to their wide ranging applications. VLPs have the potential to serve as candidate vaccine in addition to subunit vaccines and also serve as a nano-bioparticle scaffold for displaying complex foreign proteins. Here, we review different methods available to produce VLPs with various host expression systems including from microorganisms to mammalian cells and the current potential of silkworms as producers of these VLPs. Recently, silkworms have been used for efficient production of VLPs too in addition to mass production of recombinant proteins, which have contributed to molecular structural analysis, molecule-molecule interactions in biology and biotechnology.

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Induction of neutralizing antibodies and cytotoxic T lymphocytes in Balb/c mice immunized with virus-like particles presenting a gp120 molecule from a HIV-1 isolate of clade A

Cited by 68 publications

References 53 publications

Potential of Equine Herpesvirus 1 as a Vector for Immunization

Potential of Equine Herpesvirus 1 as a Vector for Immunization

DNA–VLP prime–boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity

Functional Virus-Like Particles Production Using Silkworm and Their Application in Life Science

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