Combination anti-retroviral therapy (ART) has revolutionized the treatment and prevention of HIV-1 infection. Taken daily, ART prevents and suppresses the infection. However, ART interruption almost ...invariably leads to rebound viremia in infected individuals due to a long-lived latent reservoir of integrated proviruses. Therefore, ART must be administered on a life-long basis. Here we review recent preclinical and clinical studies suggesting that immunotherapy may be an alternative or an adjuvant to ART because, in addition to preventing new infections, anti-HIV-1 antibodies clear the virus, directly kill infected cells and produce immune complexes that can enhance host immunity to the virus.
Novel broadly neutralizing antibodies targeting HIV-1 hold promise for their use in the prevention and treatment of HIV-1 infection. Pre-clinical results have encouraged the evaluation of these ...antibodies in healthy and HIV-1-infected humans. In first clinical trials, highly potent broadly neutralizing antibodies have demonstrated their safety and significant antiviral activity by reducing viremia and delaying the time to viral rebound in individuals interrupting antiretroviral therapy. While emerging antibody-resistant viral variants have indicated limitations of antibody monotherapy, strategies to enhance the efficacy of broadly neutralizing antibodies in humans are under investigation. These include the use of antibody combinations to prevent viral escape, antibody modifications to increase the half-life and the co-administration of latency-reversing agents to target the cellular reservoir of HIV-1. We provide an overview of the results of pre-clinical and clinical studies of broadly HIV-1 neutralizing antibodies, discuss their implications and highlight approaches for the ongoing advancement into humans.
Bio‐based polymer building blocks derived from abundant biomass represent a promising class of monomers for the synthesis of sustainable high‐performance polymers. Lignin‐derived vanillin is used as ...a bio‐based, aromatic molecular platform for chemical modifications. The use of vanillin aldehyde derivatives as monomers with different alkyl chain length, cured with bio‐based and less‐toxic di‐ and triamines, leads to covalent adaptable Schiff base networks and thus enables sustainable and thermally reprocessable high‐performance materials without using highly toxic amines. A process is presented to prepare homogeneous films of crosslinked materials that are thermally reprocessable while maintaining their mechanical performance. The network structures, mechanical properties, and thermal stability of the obtained polymeric sheets are characterized in detail. By systematically adjusting the composition of the network building blocks, the mechanical properties could be varied from tough materials with a high elastic modulus of 1.6 GPa to materials with high flexibility and elastomeric behavior with an elongation at break of 400%. Furthermore, the stress–relaxation behavior of stoichiometric and nonstoichiometric Schiff base vitrimers is investigated. The combination of bio‐based building blocks and the degradability of Schiff base networks under acidic conditions resulted in sustainable, environmentally friendly, chemically and thermomechanically recyclable vitrimers with self‐healing and shape‐memory properties.
Network design displays an important factor for tailoring the mechanical and thermomechanical properties of vanillin‐based Schiff base vitrimers. In this paper, new environmentally friendly reprocessable and recyclable Schiff base vitrimers are presented. By systematically adjusting the formulation of the network building blocks, their influences on the mechanical and stress–relaxation properties of the vitrimers are examined.
Antibodies in HIV-1 Vaccine Development and Therapy Klein, Florian; Mouquet, Hugo; Dosenovic, Pia ...
Science (American Association for the Advancement of Science),
09/2013, Letnik:
341, Številka:
6151
Journal Article
Recenzirano
Odprti dostop
Despite 30 years of study, there is no HIV-1 vaccine and, until recently, there was little hope for a protective immunization. Renewed optimism in this area of research comes in part from the results ...of a recent vaccine trial and the use of single-cell antibody-cloning techniques that uncovered naturally arising, broad and potent HIV-1—neutralizing antibodies (bNAbs). These antibodies can protect against infection and suppress established HIV-1 infection in animal models. The finding that these antibodies develop in a fraction of infected individuals supports the idea that new approaches to vaccination might be developed by adapting the natural immune strategies or by structure-based immunogen design. Moreover, the success of passive immunotherapy in small-animal models suggests that bNAbs may become a valuable addition to the armamentarium of drugs that work against HIV-1.
Summary
Objectives
Patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications like invasive aspergillosis. Our study evaluates coronavirus ...disease 19 (COVID‐19) associated invasive aspergillosis at a single centre in Cologne, Germany.
Methods
A retrospective chart review of all patients with COVID‐19 associated ARDS admitted to the medical or surgical intensive care unit at the University Hospital of Cologne, Cologne, Germany.
Results
COVID‐19 associated invasive pulmonary aspergillosis was found in five of 19 consecutive critically ill patients with moderate to severe ARDS.
Conclusion
Clinicians caring for patients with ARDS due to COVID‐19 should consider invasive pulmonary aspergillosis and subject respiratory samples to comprehensive analysis to detect co‐infection.
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide. Given scarce resources, nonlaboratory diagnostics ...are crucial. In this cross-sectional study, two-thirds of European patients with confirmed COVID-19 reported olfactory and gustatory dysfunction, indicating the significance of these symptoms in early diagnostics.
SARS-CoV-2 neutralizing antibodies play a critical role in COVID-19 prevention and treatment but are challenged by viral evolution and the emergence of novel escape variants. Importantly, the ...recently identified Omicron sublineages BA.2.12.1 and BA.4/5 are rapidly becoming predominant in various countries. By determining polyclonal serum activity of 50 convalescent or vaccinated individuals against BA.1, BA.1.1, BA.2, BA.2.12.1, and BA.4/5, we reveal a further reduction in BA.4/5 susceptibility to vaccinee sera. Most notably, delineation of sensitivity to an extended 163-antibody panel demonstrates pronounced antigenic differences with distinct escape patterns among Omicron sublineages. Antigenic distance and/or higher resistance may therefore favor immune-escape-mediated BA.4/5 expansion after the first Omicron wave. Finally, while most clinical-stage monoclonal antibodies are inactive against Omicron sublineages, we identify promising antibodies with high pan-SARS-CoV-2 neutralizing potency. Our study provides a detailed understanding of Omicron-sublineage antibody escape that can inform on effective strategies against COVID-19.
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•Booster immunization elicits Omicron-sublineage-neutralizing activity•Omicron sublineages demonstrate distinct antibody escape profiles•Most clinical antibodies are inactive against Omicron sublineages•Identification of broad and potent SARS-CoV-2 antibodies with pan-Omicron activity
Gruell and Vanshylla et al. study the immune escape properties of emerging Omicron sublineages including BA.2.12.1 and BA.4/5. Antigenic profiling using a large panel of monoclonal antibodies revealed distinct viral escape patterns. While most clinical antibodies lose activity against Omicron, highly potent SARS-CoV-2 antibodies with retained pan-Omicron activity were identified.
Broadly neutralizing antibodies (bNAbs) against HIV-1 provide both effective pre-exposure prophylaxis and treatment of HIV-1 infection in murine and nonhuman primate models, suggesting their ...potential use in humans. Although much is known about the role of variable domains in the neutralization breadth and potency of these bNAbs, the contribution of Fc domains to their activities is, by contrast, poorly characterized. Assessment of the in vivo activity of several bNAbs revealed that FcγR-mediated effector function contributes substantially to their capacity to block viral entry, suppress viremia, and confer therapeutic activity. Enhanced in vivo potency of anti-HIV-1 bNAbs was associated with preferential engagement of activating, but not inhibitory FcγRs, and Fc domain-engineered bNAb variants with selective binding capacity for activating FcγRs displayed augmented protective activity. These findings reveal key roles for Fc effector function in the in vivo activity of anti-HIV-1 bNAbs and provide strategies for generating bNAbs with improved efficacy.
The SARS-CoV-2 pandemic has unprecedented implications for public health, social life, and the world economy. Because approved drugs and vaccines are limited or not available, new options for ...COVID-19 treatment and prevention are in high demand. To identify SARS-CoV-2-neutralizing antibodies, we analyzed the antibody response of 12 COVID-19 patients from 8 to 69 days after diagnosis. By screening 4,313 SARS-CoV-2-reactive B cells, we isolated 255 antibodies from different time points as early as 8 days after diagnosis. Of these, 27 potently neutralized authentic SARS-CoV-2 with IC100 as low as 0.04 μg/mL, showing a broad spectrum of variable (V) genes and low levels of somatic mutations. Interestingly, potential precursor sequences were identified in naive B cell repertoires from 48 healthy individuals who were sampled before the COVID-19 pandemic. Our results demonstrate that SARS-CoV-2-neutralizing antibodies are readily generated from a diverse pool of precursors, fostering hope for rapid induction of a protective immune response upon vaccination.
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•Isolation of highly potent SARS-CoV-2-neutralizing antibodies•Longitudinal sampling reveals early class-switched neutralizing response•SARS-CoV-2 S-protein-reactive antibodies show little somatic mutation over time•Potential antibody precursor sequences identified in SARS-CoV-2-naive individuals
In a longitudinal analysis of SARS-CoV-2-infected people, Kreer et al. find highly potent neutralizing antibodies that use a broad spectrum of variable (V) genes and show low levels of somatic mutations. They also identify potential precursor sequences of these SARS-CoV-2-neutralizing antibodies from virus-naive individuals, sampled before the COVID-19 pandemic. This could indicate that neutralizing antibodies can be readily generated from existing germline antibody sequences found in the general population.
Despite 30 years of effort, there is no effective vaccine for HIV-1. However, antibodies can prevent HIV-1 infection in humanized mice and macaques when passively transferred. New single-cell-based ...methods have uncovered many broad and potent donor-derived antibodies, and structural studies have revealed the molecular bases for their activities. The new data suggest why such antibodies are difficult to elicit and inform HIV-1 vaccine development efforts. In addition to protecting against infection, the newly identified antibodies can suppress active infections in mice and macaques, suggesting they could be valuable additions to anti-HIV-1 therapies and to strategies to eradicate HIV-1 infection.
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