Bringing the path toward an HIV-1 vaccine into focus

Angel, Cesar J. Lopez; Tomaras, Georgia D.

doi:10.1371/journal.ppat.1008663

Cited by 13 publications

(14 citation statements)

References 35 publications

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“…In the case of AIDS, the capacity of immunodeficiency virus type 1 (HIV-1) to escape components of the human immune response through mutation, the debilitated response due to the HIV-1 tropism for cells involved in the immune response, and the proviral DNA integration as part of the virus life cycle are reasons why to date there are no effective anti-AIDS vaccines [ 17 , 18 ]. Antiretroviral therapy has been successful in reducing AIDS and HIV-1 infection-related mortality, but antiretroviral resistance through genetic variation of the virus and selection of escape mutants remains an issue.…”

Section: Introduction: Mistakes As Hallmark Of the Evolution Of Life And Of Present Day Virusesmentioning

confidence: 99%

Mutation Rates, Mutation Frequencies, and Proofreading-Repair Activities in RNA Virus Genetics

Domingo

García-Crespo

Lobo-Vega

et al. 2021

Viruses

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The error rate displayed during template copying to produce viral RNA progeny is a biologically relevant parameter of the replication complexes of viruses. It has consequences for virus–host interactions, and it represents the first step in the diversification of viruses in nature. Measurements during infections and with purified viral polymerases indicate that mutation rates for RNA viruses are in the range of 10−3 to 10−6 copying errors per nucleotide incorporated into the nascent RNA product. Although viruses are thought to exploit high error rates for adaptation to changing environments, some of them possess misincorporation correcting activities. One of them is a proofreading-repair 3′ to 5′ exonuclease present in coronaviruses that may decrease the error rate during replication. Here we review experimental evidence and models of information maintenance that explain why elevated mutation rates have been preserved during the evolution of RNA (and some DNA) viruses. The models also offer an interpretation of why error correction mechanisms have evolved to maintain the stability of genetic information carried out by large viral RNA genomes such as the coronaviruses

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Section: Introduction: Mistakes As Hallmark Of the Evolution Of Life And Of Present Day Virusesmentioning

confidence: 99%

Mutation Rates, Mutation Frequencies, and Proofreading-Repair Activities in RNA Virus Genetics

Domingo

García-Crespo

Lobo-Vega

et al. 2021

Viruses

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“…In addition, Th-cell mediated immunity is important to promote a functional CD8 ? CTL response and prolong antibody immune responses leading to protection and viral load reduction (Abdulla et al 2019;Lopez Angel and Tomaras 2020). Development of new immunoinformatics tools for analysis of HIV-1 proteins and identifying their poly-functional T-cell epitopes, especially when used in combination with in vivo analyses, can improve the immunogen design for HIV-1 vaccines (Khairkhah et al 2018).…”

Section: Discussionmentioning

confidence: 99%

In silico design and in vitro expression of novel multiepitope DNA constructs based on HIV-1 proteins and Hsp70 T-cell epitopes

et al. 2021

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Objectives Epitope-driven vaccines carrying highly conserved and immunodominant epitopes have emerged as promising approaches to overcome human immunodeficiency virus-1 (HIV-1) infection. Methods Two multiepitope DNA constructs encoding T cell epitopes from HIV-1 Gag, Pol, Env, Nef and Rev proteins alone and/or linked to the immunogenic epitopes derived from heat shock protein 70 (Hsp70) as an immunostimulatory agent were designed. In silico analyses were applied including MHC-I and MHC-II binding, MHC-I immunogenicity and antigen processing, population coverage, conservancy, allergenicity, toxicity and hemotoxicity. The peptide-MHC-I/MHC-II molecular docking and cytokine production analyses were carried out for predicted epitopes. The selected highly immunogenic T-cell epitopes were then used to design two multiepitope fusion constructs. Next, prediction of the physicochemical and structural properties, B cell epitopes, and constructs-toll-like receptors (TLRs) molecular docking were performed for each construct. Finally, the eukaryotic expression plasmids harboring totally 12 cytotoxic T Lymphocyte (CTL) and 10 helper T lymphocytes (HTL) epitopes from HIV-1 proteins (i.e., pEGFP-N1-gag-pol-env-nef-rev), and linked to 2 CTL and 2 HTL epitopes from Hsp70 (i.e., pEGFP-N1-hsp70-gag-pol-env-nef-rev) were generated and transfected into HEK-293 T cells for evaluating the percentage of multiepitope peptides expression using flow cytometry and western blotting. Results The designed DNA constructs could be successfully expressed in mammalian cells. The

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“…Many studies have shown the potential protective role of neutralizing antibodies in both animal and human models [ 216 ]. However, in the RV144 vaccine trial, IgG antibodies correlated with lower HIV-1 risk and were able to drive ADCC, ADCP and complement activation [ 79 , 217 ], underscoring the role of non-neutralizing effector functions in protective vaccination. In a recent study, HIV-specific antibodies demonstrated antibody-dependent neutrophil phagocytosis (ADNP) and ADCC functions in the genital tract [ 218 ].…”

Section: Mucosal Immunitymentioning

confidence: 99%

Preventive HIV Vaccines-Leveraging on Lessons from the Past to Pave the Way Forward

Sobia

Archary

2021

Vaccines

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Almost four decades on, since the 1980’s, with hundreds of HIV vaccine candidates tested in both non-human primates and humans, and several HIV vaccines trials later, an efficacious HIV vaccine continues to evade us. The enormous worldwide genetic diversity of HIV, combined with HIV’s inherent recombination and high mutation rates, has hampered the development of an effective vaccine. Despite the advent of antiretrovirals as pre-exposure prophylaxis and preventative treatment, which have shown to be effective, HIV infections continue to proliferate, highlighting the great need for a vaccine. Here, we provide a brief history for the HIV vaccine field, with the most recent disappointments and advancements. We also provide an update on current passive immunity trials, testing proof of the concept of the most clinically advanced broadly neutralizing monoclonal antibodies for HIV prevention. Finally, we include mucosal immunity, the importance of vaccine-elicited immune responses and the challenges thereof in the most vulnerable environment–the female genital tract and the rectal surfaces of the gastrointestinal tract for heterosexual and men who have sex with men transmissions, respectively.

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Bringing the path toward an HIV-1 vaccine into focus

Abstract: Why do we need a human immunodeficiency virus (HIV-1) vaccine in the age of antiretroviral therapy and preexposure prophylaxis?

Cited by 13 publications

References 35 publications

Mutation Rates, Mutation Frequencies, and Proofreading-Repair Activities in RNA Virus Genetics

Mutation Rates, Mutation Frequencies, and Proofreading-Repair Activities in RNA Virus Genetics

In silico design and in vitro expression of novel multiepitope DNA constructs based on HIV-1 proteins and Hsp70 T-cell epitopes

Preventive HIV Vaccines-Leveraging on Lessons from the Past to Pave the Way Forward

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