Abstract:Biopanning of serum IgG can yield mimotopes of HIV-1-related antigen epitopes. This methodology provides a basis for exploration into HIV-1-related antigen-antibody interactions and furthers NAb immunotherapy and vaccine design.
“…It complicates the design of immunogens capable of inducing sufficient B-cell response. Phage peptide libraries offer the unique possibility to obtain mimics of such epitopes [41][42][43][44][45][46].…”
Section: B-cell Epitopes To Hiv-1 Generating Broadly Neutralizing Antmentioning
One of the promising approaches for designing HIV vaccines is construction of synthetic polyepitope HIV-1 immunogen using a wide range of conservative T-and B-cell epitopes of the main virus antigens. In theory this approach helps cope with HIV-1 antigenic variability, focuses immune responses on protective determinants and enables to exclude from the vaccine compound adverse regions of viral proteins that can induce autoantibodies or antibodies enhancing infectivity of virus. The paper presents the experience of our team in development of artificial polyepitope HIV-1 immunogens, which can induce both a humoral response, and responses of cytotoxic (CD8 + CTL) and helpers (CD4 + Th) T-cells. The design of HIV-immunogens has been done using our original software, TEpredict and PolyCTLDesigner. We describe development of the candidate HIV-1/ AIDS vaccine-CombiHIVvac, which included two artificial polyepitope immunogens TBI and TCI for stimulating humoral and cellular responses. The results of the specific activity and safety of CombiHIVvac vaccine, obtained during preclinical and clinical trials, are presented.
“…It complicates the design of immunogens capable of inducing sufficient B-cell response. Phage peptide libraries offer the unique possibility to obtain mimics of such epitopes [41][42][43][44][45][46].…”
Section: B-cell Epitopes To Hiv-1 Generating Broadly Neutralizing Antmentioning
One of the promising approaches for designing HIV vaccines is construction of synthetic polyepitope HIV-1 immunogen using a wide range of conservative T-and B-cell epitopes of the main virus antigens. In theory this approach helps cope with HIV-1 antigenic variability, focuses immune responses on protective determinants and enables to exclude from the vaccine compound adverse regions of viral proteins that can induce autoantibodies or antibodies enhancing infectivity of virus. The paper presents the experience of our team in development of artificial polyepitope HIV-1 immunogens, which can induce both a humoral response, and responses of cytotoxic (CD8 + CTL) and helpers (CD4 + Th) T-cells. The design of HIV-immunogens has been done using our original software, TEpredict and PolyCTLDesigner. We describe development of the candidate HIV-1/ AIDS vaccine-CombiHIVvac, which included two artificial polyepitope immunogens TBI and TCI for stimulating humoral and cellular responses. The results of the specific activity and safety of CombiHIVvac vaccine, obtained during preclinical and clinical trials, are presented.
“…HR2 plays a critical role in viral fusion; antibodies targeting this region may impair hairpin formation and viral entry ( 55 ). NAbs targeting HR2 have been described in slow progressors ( 56 ) and controllers ( 57 ), while non-neutralizing HR2 antibodies with robust ADCC activity were found in a non-controller ( 58 ). This report demonstrates that pre-infection antibody reactivity to the C epitope is associated with controller status and lower VL after infection, consistent with antibody-mediated suppression of viral replication.…”
BackgroundHigh HIV viral load (VL) is associated with increased transmission risk and faster disease progression. HIV controllers achieve viral suppression without antiretroviral (ARV) treatment. We evaluated viremic control in a community-randomized trial with >48,000 participants.MethodsA massively multiplexed antibody profiling system, VirScan, was used to quantify pre- and post-infection antibody reactivity to HIV peptides in 664 samples from 429 participants (13 controllers, 135 viremic non-controllers, 64 other non-controllers, 217 uninfected persons). Controllers had VLs <2,000 copies/mL with no ARV drugs detected at the first HIV-positive visit and one year later. Viremic non-controllers had VLs 2,000 copies/mL with no ARV drugs detected at the first HIV-positive visit. Other non-controllers had either ARV drugs detected at the first HIV-positive visit (n=47) or VLs <2,000 copies/mL with no ARV drugs detected at only one HIV-positive visit (n=17).ResultsWe identified pre-infection HIV antibody reactivities that correlated with post-infection VL. Pre-infection reactivity to an epitope in the HR2 domain of gp41 was associated with controller status and lower VL. Pre-infection reactivity to an epitope in the C2 domain of gp120 was associated with non-controller status and higher VL. Different patterns of antibody reactivity were observed over time for these two epitopes.ConclusionThese studies suggest that pre-infection HIV antibodies are associated with controller status and modulation of HIV VL. These findings may inform research on antibody-based interventions for HIV treatment.
“…Identification of mimotopes is a powerful technique as it easily allows to map many antigenic determinants at the same time using a polyclonal serum or to identify a single mAb epitope at a medium resolution [24,25]. The canonical 18 mer peptides allow the study of conformational epitopes, as they are long enough to fold into a specific secondary structure.…”
Defining immunogenic domains of viral proteins capable of eliciting a protective immune response is crucial in the development of novel epitope-based prophylactic strategies. This is particularly important for the selective targeting of conserved regions shared among hypervariable viruses. Studying postinfection and postimmunization sera, as well as cloning and characterization of monoclonal antibodies (mAbs), still represents the best approach to identify protective epitopes. In particular, a protective mAb directed against conserved regions can play a key role in immunogen design and in human therapy as well. Experimental approaches aiming to characterize protective mAb epitopes or to identify T-cell-activating peptides are often burdened by technical limitations and can require long time to be correctly addressed. Thus, in the last decade many epitope predictive algorithms have been developed. These algorithms are continually evolving, and their use to address the empirical research is widely increasing. Here, we review several strategies based on experimental techniques alone or addressed by in silico analysis that are frequently used to predict immunogens to be included in novel epitope-based vaccine approaches. We will list the main strategies aiming to design a new vaccine preparation conferring the protection of a neutralizing mAb combined with an effective cell-mediated response.
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