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1.
Int J Mol Sci ; 25(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38891926

RESUMO

Despite advancements in vaccinology, there is currently no effective anti-HIV vaccine. One strategy under investigation is based on the identification of epitopes recognized by broadly neutralizing antibodies to include in vaccine preparation. Taking into account the benefits of anti-idiotype molecules and the diverse biological attributes of different antibody formats, our aim was to identify the most immunogenic antibody format. This format could serve as a foundational element for the development of an oligo-polyclonal anti-idiotype vaccine against HIV-1. For our investigation, we anchored our study on an established b12 anti-idiotype, referred to as P1, and proposed four distinct formats: two single chains and two minibodies, both in two different orientations. For a deeper characterization of these molecules, we used immunoinformatic tools and tested them on rabbits. Our studies have revealed that a particular minibody conformation, MbVHVL, emerges as the most promising candidate. It demonstrates a significant binding affinity with b12 and elicits a humoral anti-HIV-1 response in rabbits similar to the Fab format. This study marks the first instance where the minibody format has been shown to provoke a humoral response against a pathogen. Furthermore, this format presents biological advantages over the Fab format, including bivalency and being encoded by a monocistronic gene, making it better suited for the development of RNA-based vaccines.


Assuntos
Vacinas contra a AIDS , Anticorpos Anti-Idiotípicos , Anticorpos Anti-HIV , HIV-1 , Imunidade Humoral , Animais , Coelhos , Anticorpos Anti-HIV/imunologia , HIV-1/imunologia , Imunidade Humoral/imunologia , Anticorpos Anti-Idiotípicos/imunologia , Vacinas contra a AIDS/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Anticorpos Neutralizantes/imunologia , Simulação por Computador , Epitopos/imunologia
2.
J Immunol Res ; 2024: 2147912, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628675

RESUMO

Ever since its discovery, human immunodeficiency virus type 1 (HIV-1) infection has remained a significant public health concern. The number of HIV-1 seropositive individuals currently stands at 40.1 million, yet definitive treatment for the virus is still unavailable on the market. Vaccination has proven to be a potent tool in combating infectious diseases, as evidenced by its success against other pathogens. However, despite ongoing efforts and research, the unique viral characteristics have prevented the development of an effective anti-HIV-1 vaccine. In this review, we aim to provide an historical overview of the various approaches attempted to create an effective anti-HIV-1 vaccine. Our objective is to explore the reasons why specific methods have failed to induce a protective immune response and to analyze the different modalities of immunogen presentation. This trial is registered with NCT05414786, NCT05471076, NCT04224701, and NCT01937455.


Assuntos
Vacinas contra a AIDS , Infecções por HIV , Humanos , Vacinação , Ensaios Clínicos como Assunto
3.
Front Immunol ; 14: 1104423, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36798134

RESUMO

Human Immunodeficiency Virus (HIV) is still one of the major global health issues, and despite significant efforts that have been put into studying the pathogenesis of HIV infection, several aspects need to be clarified, including how innate immunity acts in different anatomical compartments. Given the nature of HIV as a sexually transmitted disease, one of the aspects that demands particular attention is the mucosal innate immune response. Given this scenario, we focused our attention on the interplay between HIV and mucosal innate response: the different mucosae act as a physical barrier, whose integrity can be compromised by the infection, and the virus-cell interaction induces the innate immune response. In addition, we explored the role of the mucosal microbiota in facilitating or preventing HIV infection and highlighted how its changes could influence the development of several opportunistic infections. Although recent progress, a proper characterization of mucosal innate immune response and microbiota is still missing, and further studies are needed to understand how they can be helpful for the formulation of an effective vaccine.


Assuntos
Infecções por HIV , Infecções Sexualmente Transmissíveis , Humanos , HIV , Mucosa , Imunidade Inata
4.
New Microbiol ; 45(3): 199-209, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35920875

RESUMO

The spread of multidrug-resistant (MDR) K. pneumoniae carbapenemase-producing bacteria (KPC) is one of the most serious threats to global public health. Due to the limited antibiotic options, colis- tin often represents a therapeutic choice. In this study, we performed Whole-Genome Sequencing (WGS) by Illumina and Nanopore platforms on four colistin-resistant K. pneumoniae isolates (CoRKp) to explore the resistance profile and the mutations involved in colistin resistance. Mapping reads with reference sequence of the most com- mon genes involved in colistin resistance did not show the presence of mobile colistin resistance (mcr) genes in all CoRKp. Complete or partial deletions of mgrB gene were observed in three out of four CoRKp, while in one CoRKp the mutation V24G on phoQ was identified. Complementation assay with proper wild type genes restored colistin susceptibility, validating the role of the amino acid substitution V24G and, as already described in the literature, confirming the key role of mgrB alterations in colistin resistance. In conclusion, this study allowed the identification of the novel mutation on phoQ gene involved in colistin resistance phenotype.


Assuntos
Colistina , Infecções por Klebsiella , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Colistina/farmacologia , Colistina/uso terapêutico , Farmacorresistência Bacteriana/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Mutação , beta-Lactamases/genética
5.
J Orthop ; 23: 264-272, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679018

RESUMO

BACKGROUND: Total knee arthroplasty surgery (TKA) using prenavigated Patient Specific Instruments (PSI) technique represents one of the most recent technological evolutions in development of prosthetic surgery. The aim of this study was to evaluate kinematic and functional recovery of patients operated with prenavigated PSI technique compared to those operated with traditional technique. METHODS: A cohort of 20 patients is divided in two groups; some are operated with traditional technique (with NexGen Knee system) and others with prenavigated PSI technique (with eMP Knee system) at Asiago Hospital. Limb circumferences are measured for edema evaluation and different evaluation forms are provided to patients: SF-36, KSS pre-surgery (T0), KSS 15 (T1) and 45 days after surgery (T2). Gait Analysis is performed 60 days post-surgery, after leaving crutches. RESULTS: The analysis of KSS and SF-36 evaluation forms shows a greater improvement in PSI Evolution group in terms of articulation (comparison between T0 and T1), knee function and early return to physical and social activities. Pain is lesser in NexGen group, in an earlier phase, but 45 days after surgery (T2) there are no significant differences between two groups. Perception of general state of health improves more and earlier in NexGen. In NexGen group edema evaluation had significant differences at the level of prosthetic leg, but not in knee and thigh. Overall: the walking pattern is more physiological in PSI Evolution group. CONCLUSIONS: The present study highlighted the superiority of prenavigated PSI technique over traditional technique in recovering functionality of prosthetic knee and in restoring a more physiological path pattern.

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