Variable epitope libraries: New vaccine immunogens capable of inducing broad human immunodeficiency virus type 1-neutralizing antibody response

Charles-Niño, Claudia; Pedroza-Roldán, César; Viveros, Monica; Gevorkian, Goar; Manoutcharian, Karen

doi:10.1016/j.vaccine.2011.05.007

Cited by 22 publications

(17 citation statements)

References 49 publications

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“…The primary objective of VELs is to activate the largest possible CD8+ T cell repertoire. The effi cacy of VELs has been proved in our previous studies: an HIV-1 antigenbased VEL induced HIV-1 neutralizing serum (neutralization of half of a tier 2 panel of primary HIV isolates) [2]; and in a murine breast tumor model, VELs were able to inhibit aggressive breast cancer in terms of tumor growth [3] and metastasis [4]. Our results are best-in-class achievements in their corresponding fi elds.…”

supporting

confidence: 65%

Variable epitope library-based COVID-19 vaccine for current and future related epidemics

Manoutcharian¹,

Valle²,

Odales³

2020

Open J Pharmacol Pharmacother

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supporting

confidence: 65%

Variable epitope library-based COVID-19 vaccine for current and future related epidemics

Manoutcharian¹,

Valle²,

Odales³

2020

Open J Pharmacol Pharmacother

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“…66 Moreover, based on previous reports on neutralizing activity of antibodies induced by the same V3 loop-derived epitope, 69,70 we showed that sera from VEL-immunized mice were capable of neutralizing 5 out 10 viral isolates from Tier 2 reference panel, including HIV-1 isolates known to be resistant to neutralization by several potent monoclonal antibodies described previously. 67 These data indicate the feasibility of the application of immunogens based on VEL concept as an alternative approach and as a general technological platform for the development of molecular vaccines against AVPs. The hypothesis behind the concept is simple: the activation of diverse pool of B and T lymphocytes requires the immunogens carrying antigenic diversity that mirrors the natural infections with HIV, other AVPs or disease conditions, such as cancer, in respect to interactions between immune system and rapidly evolving epitopes.…”

Section: Hivmentioning

confidence: 83%

“…1) for generation of vaccine immunogens specifically targeting genetically/antigenically variable pathogens, termed as variable epitope library (VEL). 66,67 These new classes of immunogens are combinatorial libraries bearing a mixture of heavily mutated variants of a single immunodominant epitope. In a proof of concept study, we have demonstrated that immunization with VEL expressing a mixture of thousands of variants of an immunodominat HIV-1 gp120 V3 loop-derived CTL epitope 68 (RGPGRAFVTI) induced CTLs recognizing more than 50% of heavily mutated variants of wild type epitope.…”

Section: Hivmentioning

confidence: 99%

“…The hypothesis behind the concept is simple: the activation of diverse pool of B and T lymphocytes requires the immunogens carrying antigenic diversity that mirrors the natural infections with HIV, other AVPs or disease conditions, such as cancer, in respect to interactions between immune system and rapidly evolving epitopes. 66,67 Hence, the VELs carrying random mutations may prevent or reduce the likelihood of epitope escape and, therefore, represent a realistic alternative to existing vaccine approaches targeting AVPs.…”

Section: Hivmentioning

confidence: 99%

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Antigenic variability: Obstacles on the road to vaccines against traditionally difficult targets

Servín-Blanco

Zamora-Alvarado

Gevorkian

et al. 2016

Human Vaccines & Immunotherapeutics

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Despite the impressive impact of vaccines on public health, the success of vaccines targeting many important pathogens and cancers has to date been limited. The burden of infectious diseases today is mainly caused by antigenically variable pathogens (AVPs), which escape immune responses induced by prior infection or vaccination through changes in molecular structures recognized by antibodies or T cells. Extensive genetic and antigenic variability is the major obstacle for the development of new or improved vaccines against "difficult" targets. Alternative, qualitatively new approaches leading to the generation of disease-and patient-specific vaccine immunogens that incorporate complex permanently changing epitope landscapes of intended targets accompanied by appropriate immunomodulators are urgently needed. In this review, we highlight some of the most critical common issues related to the development of vaccines against many pathogens and cancers that escape protective immune responses owing to antigenic variation, and discuss recent efforts to overcome the obstacles by applying alternative approaches for the rational design of new types of immunogens.

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“…Mice immunization provided potent and broad epitope-specific long lasting response (12 months) and effector memory T cells were induced. Moreover, recent studies demonstrated that mice immunized with these variable epitope libraries are capable of neutralizing half of the subtype B viral isolates used for challenge, including HIV-1 isolates which are known to be resistant to neutralization by several potent monoclonal antibodies [218]. …”

Section: Phage Particles As Hiv-1 Antigen Carriersmentioning

confidence: 99%

Phages and HIV-1: From Display to Interplay

Delhalle

Schmit

Chevigné

2012

IJMS

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The complex hide-and-seek game between HIV-1 and the host immune system has impaired the development of an efficient vaccine. In addition, the high variability of the virus impedes the long-term control of viral replication by small antiviral drugs. For more than 20 years, phage display technology has been intensively used in the field of HIV-1 to explore the epitope landscape recognized by monoclonal and polyclonal HIV-1-specific antibodies, thereby providing precious data about immunodominant and neutralizing epitopes. In parallel, biopanning experiments with various combinatorial or antibody fragment libraries were conducted on viral targets as well as host receptors to identify HIV-1 inhibitors. Besides these applications, phage display technology has been applied to characterize the enzymatic specificity of the HIV-1 protease. Phage particles also represent valuable alternative carriers displaying various HIV-1 antigens to the immune system and eliciting antiviral responses. This review presents and summarizes the different studies conducted with regard to the nature of phage libraries, target display mode and biopanning procedures.

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Variable epitope libraries: New vaccine immunogens capable of inducing broad human immunodeficiency virus type 1-neutralizing antibody response

Cited by 22 publications

References 49 publications

Variable epitope library-based COVID-19 vaccine for current and future related epidemics

Variable epitope library-based COVID-19 vaccine for current and future related epidemics

Antigenic variability: Obstacles on the road to vaccines against traditionally difficult targets

Phages and HIV-1: From Display to Interplay

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