High-Functional-Avidity Cytotoxic T Lymphocyte Responses to HLA-B-Restricted Gag-Derived Epitopes Associated with Relative HIV Control

Berger, Christoph T.; Frahm, Nicole; Price, David A.; Mothe, Beatriz; Ghebremichael, Musie; Hartman, Kari L.; Henry, Leah M.; Brenchley, Jason M.; Ruff, Laura E.; Venturi, Vanessa; Pereyra, Florencia; Sidney, John; Sette, Alessandro; Douek, Daniel C.; Walker, Bruce D.; Kaufmann, Daniel E.; Berthou, Christian

doi:10.1128/jvi.00460-11

Cited by 123 publications

(110 citation statements)

References 88 publications

(117 reference statements)

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“…Favorable characteristics include broadly directed targeting of Gag-derived epitopes (7,8), especially those restricted by HLA-B molecules (9), high-avidity interactions with cognate Ag (10,11), and the ability to proliferate (12,13) and deploy multiple effector functions upon Ag encounter (14). The latter include direct killing of HIV-infected cells (15,16), which is incorporated in measurements of viral suppressive activity in vitro (17,18).…”

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confidence: 99%

Epitope Specificity Delimits the Functional Capabilities of Vaccine-Induced CD8 T Cell Populations

Hill

Darrah

Ende

et al. 2014

The Journal of Immunology

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Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2Kd epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9/H-2Dd epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9/H-2Dd specificity. Higher proportions of central memory-like cells were present after low-dose vaccination and at later time points. However, there were no noteworthy phenotypic differences between epitope-specific CD8 T cell populations across vaccine doses or time points. Collectively, these data indicate that the functional and phenotypic properties of vaccine-induced CD8 T cell populations are sensitive to dose manipulation, yet constrained by epitope specificity in a clonotype-dependent manner.

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confidence: 99%

Epitope Specificity Delimits the Functional Capabilities of Vaccine-Induced CD8 T Cell Populations

Hill

Darrah

Ende

et al. 2014

The Journal of Immunology

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“…The other chimaeric L1s did not form distinct particles, and elicited significantly weaker humoral immune responses for the same dose of protein. The L1:L2 [108][109][110][111][112][113][114][115][116][117][118][119][120] particle formation was in contrast to repeated previous expression of this and the other chimaeras in insect cells, where only loose aggregates of capsomers were formed for L1:L2 [108][109][110][111][112][113][114][115][116][117][118][119][120] [95,96].…”

Section: Papillomavirus Vaccinesmentioning

confidence: 98%

“…All chimaeras were very highly expressed, with yields of up to 1.2 g/kg plant tissue. The L1 chimaera containing L2 amino acids 108-120 (L1:L2 [108][109][110][111][112][113][114][115][116][117][118][119][120] ) was the most successful candidate in that it assembled into small VLPs (~30 nm), and elicited anti-L1 and anti-L2 responses in IM immunised mice, and immune sera neutralised homologous HPV-16 and heterologous HPV-52 pseudovirions. The other chimaeric L1s did not form distinct particles, and elicited significantly weaker humoral immune responses for the same dose of protein.…”

Section: Papillomavirus Vaccinesmentioning

confidence: 99%

Plant-based vaccines against viruses

Rybicki

2014

Virology Journal

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Plant-made or "biofarmed" viral vaccines are some of the earliest products of the technology of plant molecular farming, and remain some of the brightest prospects for the success of this field. Proofs of principle and of efficacy exist for many candidate viral veterinary vaccines; the use of plant-made viral antigens and of monoclonal antibodies for therapy of animal and even human viral disease is also well established. This review explores some of the more prominent recent advances in the biofarming of viral vaccines and therapies, including the recent use of ZMapp for Ebolavirus infection, and explores some possible future applications of the technology.

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“…The HLA genotypes that are the most protective from disease progression seem to enable CTL to target immutable HIV epitopes [57,58]. Furthermore, ECs appear to have increased functional avidities of Gag-specific and HLA-B-restricted CTL responses [59]. Importantly, HLA-associated effects can reflect CTL activity as well as other immune responses such as the killer Ig-like receptor (KIR)-HLA interactions involving NK cells [60] and CNAR [44].…”

Section: Cytotoxic T-cell Responsesmentioning

confidence: 99%

HIV/AIDS: 30 Years of progress and future challenges

Killian

Levy

2011

Eur J Immunol

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Acquired immune deficiency syndrome (AIDS) was first described 30 years ago in a report from the US Centers for Disease Control. Two years later the causative virus was identified and afterwards named the human immunodeficiency virus (HIV). This article reviews the progress made in the three decades since the recognition of AIDS and the discovery of HIV, with respect to the virus, the infected cell, and the host, as well as directions for future studies.

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High-Functional-Avidity Cytotoxic T Lymphocyte Responses to HLA-B-Restricted Gag-Derived Epitopes Associated with Relative HIV Control

Abstract: Virus-specific cytotoxic T lymphocytes (CTL) with high levels of functional avidity have been associated with viral clearance in hepatitis

Cited by 123 publications

References 88 publications

Epitope Specificity Delimits the Functional Capabilities of Vaccine-Induced CD8 T Cell Populations

Epitope Specificity Delimits the Functional Capabilities of Vaccine-Induced CD8 T Cell Populations

Plant-based vaccines against viruses

HIV/AIDS: 30 Years of progress and future challenges

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