Induction of Systemic and Mucosal Cross-Clade Neutralizing Antibodies in BALB/c Mice Immunized with Human Immunodeficiency Virus Type 1 Clade A Virus-Like Particles Administered by Different Routes of Inoculation

Buonaguro, Luigi; Visciano, Maria Luisa; Tornesello, Maria Lina; Tagliamonte, Maria; Biryahwaho, Benon

doi:10.1128/jvi.79.11.7059-7067.2005

Cited by 71 publications

(48 citation statements)

References 64 publications

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“…These data confirm the efficient induction of humoral and cellular systemic as well as mucosal immunity by intra-nasal administration of HIV-VLP A s, as previously reported [16]. This is likely due to efficient presentation in the major histocompatibility complex (MHC)…”

Section: Discussionsupporting

confidence: 75%

“…The results obtained at systemic and mucosal levels with these prime-boost protocols, performed with a single VLP boosting dose of 2ug, are particularly interesting compared to our previous results obtained with 4 doses of VLP (20 and 100 ug/dose) without adjuvant [16]. In particular, the vaginal IgA anti-gag response is considerably increased in both homologous and heterologous protocols adjuvanted in L3 (8.06 folds the homologous and 14.38 folds the heterologous) ( Table 2).…”

Section: Induction Of Mucosal Antibody Response By Intra-nasal Adminimentioning

confidence: 53%

“…Furthermore, the immunogenicity of the HIV-VLP A s has been evaluated in Balb/c mice by intra-nasal (i.n.) routes, in a homologous (VLP+VLP) primeboost protocol without any adjuvant formulation, showing the induction of humoral IgA and/or IgG antibody response with neutralizing activity, in sera and at mucosal (vaginal and intestinal) sites, as well as cellular immune response [16].…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 75%

Section: Induction Of Mucosal Antibody Response By Intra-nasal Adminimentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

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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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“…Inducing mucosal immune responses has been the focus of many efforts over the past 5-10 years, including comparisons of different immunization routes, often alternating prime-boost strategies mucosally and systemically, as well as comparisons of different immunization sites, with subsequent evaluation of induced mucosal immune responses [7][8][9][10][11][12][13][14][15][16][17][18][19]. While this human, Phase 1 trial aimed to secondarily assess the differential impact on induced mucosal responses with two systemic immunization sites (deltoid and inguinal) [10], but was halted after enrollment of 8 subjects in favor of a larger trial to address the question using a canarypox vaccine.…”

Section: Introductionmentioning

confidence: 99%

Differential immunogenicity of vaccinia and HIV-1 components of a human recombinant vaccine in mucosal and blood compartments

Anton¹,

Ibarrondo²,

Boscardin

et al. 2008

Vaccine

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Mucosal immune responses induced by HIV-1 vaccines are likely critical for prevention. We report a Phase 1 safety and immunogenicity trial in 8 participants using the vaccinia-based TBC-3B vaccine given subcutaneously to determine the relationship between HIV-1 specific systemic and gastrointestinal mucosal responses. Across all subjects, detectable levels of blood vaccinia-and HIV-1-specific antibodies were elicited but none were seen mucosally. While the vaccinia component was immunogenic for CD8 + T lymphocyte (CTL) responses in both blood and mucosa, it was greater in blood. The HIV-1 component of the vaccine was poorly immunogenic in both blood and mucosa. Although only 8 volunteers were studied intensively, the discordance between mucosal and blood responses may highlight mechanisms contributing to recent vaccine failures.

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“…VLP-based vaccines are currently under investigation for several families of human viruses, including hepatitis viruses, papillomavirus, rotavirus, parvovirus, and influenza virus (3,8,17,21,39). Several studies have demonstrated the induction of neutralizing antibodies by HIV VLP immunization using murine models (9,13,52) or primates (33). Importantly, VLP antigens can be processed to present antigens through the major histocompatibility class (MHC) II pathway as well as the MHC I endogenous pathway, inducing both CD4 ϩ -and CD8 ϩ -T-cell-mediated immune responses (4,12,40).…”

mentioning

confidence: 99%

Incorporation of Glycosylphosphatidylinositol-Anchored Granulocyte- MacrophageColony-Stimulating Factor or CD40 Ligand Enhances Immunogenicity of Chimeric Simian Immunodeficiency Virus-Like Particles

Skountzou

Quan

Gangadhara

et al. 2007

J Virol

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The rapid worldwide spread of human immunodeficiency virus (HIV) mandates the development of successful vaccination strategies. Since live attenuated HIV is not accepted as a vaccine due to safety concerns, virus-like particles (VLPs) offer an attractive safe alternative because they lack the viral genome yet they are perceived by the immune system as a virus particle. We hypothesized that adding immunostimulatory signals to VLPs would enhance their efficacy. To accomplish this we generated chimeric simian immunodeficiency virus (SIV) VLPs containing either glycosylphosphatidylinositol (GPI)-anchored granulocyte-macrophage colonystimulating factor (GM-CSF) or CD40 ligand (CD40L) and investigated their biological activity and ability to enhance immune responses in vivo. Immunization of mice with chimeric SIV VLPs containing GM-CSF induced SIV Env-specific antibodies as well as neutralizing activity at significantly higher levels than those induced by standard SIV VLPs, SIV VLPs containing CD40L, or standard VLPs mixed with soluble GM-CSF. In addition, mice immunized with chimeric SIV VLPs containing either GM-CSF or CD40L showed significantly increased CD4 ؉ -and CD8 ؉ -T-cell responses to SIV Env, compared to standard SIV VLPs. Taken together, these results demonstrate that the incorporation of immunostimulatory molecules enhances humoral and cellular immune responses. We propose that anchoring immunostimulatory molecules into SIV VLPs can be a promising approach to augmenting the efficacy of VLP antigens.

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Induction of Systemic and Mucosal Cross-Clade Neutralizing Antibodies in BALB/c Mice Immunized with Human Immunodeficiency Virus Type 1 Clade A Virus-Like Particles Administered by Different Routes of Inoculation

Cited by 71 publications

References 64 publications

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

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

Differential immunogenicity of vaccinia and HIV-1 components of a human recombinant vaccine in mucosal and blood compartments

Incorporation of Glycosylphosphatidylinositol-Anchored Granulocyte- MacrophageColony-Stimulating Factor or CD40 Ligand Enhances Immunogenicity of Chimeric Simian Immunodeficiency Virus-Like Particles

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