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The global energy system is in transition. It is attempting to reach net‐zero greenhouse gas emissions by 2050. The systemic changes mean that the role of bioenergy will change. The potential of bioenergy to make a flexible contribution to the energy system is key for the achievement of global emission reduction ambitions and the functioning of the low‐carbon energy system and economy. As the volume of sustainably available biomass resources is limited, defining the contributions from bioenergy to a low‐carbon energy system and finding balances – and ideally synergies – between the different possible energy and climate system services that biomass can provide will be very important. The recognized system services include, among others, the flexible operation of bioenergy plants to integrate variable renewable energy sources and to provide negative carbon dioxide (CO2) emissions. Interest in flexible operation of bioenergy value chains, bioenergy with carbon capture and utilization as well as synergies with renewable hydrogen‐based value chains has increased recently. The objective of this paper is to present a holistic definition of flexible bioenergy as a system service based on the work conducted in International Energy Agency (IEA) Bioenergy Technology Collaboration Programme's Task 44 Flexible Bioenergy and System Integration, and to provide some practical examples. The paper also presents the different bioenergy system services and considers their definitions and interactions, as this is important in energy system design. The definition of flexible bioenergy shows that the flexibility provision from bioenergy goes far beyond the traditional definition of providing short‐term flexibility in the power sector. Indicators to demonstrate the value of services as well as further quantitative assessment of synergies and trade‐offs are needed to valorize the different services from bioenergy and create viable business cases. [ABSTRACT FROM AUTHOR]

The potency of antibody neutralization in cell culture has been used as the key criterion for selection of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for clinical development. As other aspects may also influence the degree of protection in vivo, we compared the efficacy of two neutralizing monoclonal antibodies (TRES6 and 4C12) targeting different epitopes of the receptor binding domain (RBD) of SARS-CoV-2 in a prophylactic setting in rhesus monkeys. All four animals treated with TRES6 had reduced viral loads in the upper respiratory tract 2 days after naso-oropharyngeal challenge with the Alpha SARS-CoV-2 variant. Starting 2 days after challenge, mutations conferring resistance to TRES6 were dominant in two of the rhesus monkeys, with both animals failing to maintain reduced viral loads. Consistent with its lower serum neutralization titer at the day of challenge, prophylaxis with 4C12 tended to suppress viral load at day 2 less efficiently than TRES6. However, a week after challenge, mean viral loads in the lower respiratory tract in 4C12-treated animals were lower than in the TRES6 group and no mutations conferring resistance to 4C12 could be detected in viral isolates from nasal or throat swabs. Thus, genetic barrier to resistance seems to be a critical parameter for the efficacy of prophylaxis with monoclonal antibodies against SARS-CoV-2. Furthermore, comparison of antibody concentrations in respiratory secretions to those in serum shows reduced distribution of the 4C12 antibody into respiratory secretions and a delay in the appearance of antibodies in bronchoalveolar lavage fluid compared to their appearance in secretions of the upper respiratory tract. IMPORTANCE Monoclonal antibodies are a powerful tool for the prophylaxis and treatment of acute viral infections. Hence, they were one of the first therapeutic agents licensed for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Oftentimes, the main criterion for the selection of antibodies for clinical development is their potency of neutralization in cell culture. By comparing two antibodies targeting the Spike protein of SARS-CoV-2, we now observed that the antibody that neutralized SARS-CoV-2 more efficiently in cell culture suppressed viral load in challenged rhesus monkeys to a lesser extent. Extraordinary rapid emergence of mutants of the challenge virus, which had lost their sensitivity to the antibody, was identified as the major reason for the reduced efficacy of the antibody in rhesus monkeys. Therefore, the viral genetic barrier to resistance to antibodies also affects their efficacy. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus (HIV) envelope protein (Env) mediates viral entry into host cells and is the primary target for the humoral immune response. Env is extensively glycosylated, and these glycans shield underlying epitopes from neutralizing antibodies. The glycosylation of Env is influenced by the type of host cell in which the virus is produced. Thus, HIV is distinctly glycosylated by CD4+ T cells, the major target cells, and macrophages. However, the specific differences in glycosylation between viruses produced in these cell types have not been explored at the molecular level. Moreover, it remains unclear whether the production of HIV in CD4+ T cells or macrophages affects the efficiency of viral spread and resistance to neutralization. To address these questions, we employed the simian immunodeficiency virus (SIV) model. Glycan analysis implied higher relative levels of oligomannose-type N-glycans in SIV from CD4+ T cells (T-SIV) compared to SIV from macrophages (M-SIV), and the complex-type N-glycans profiles seem to differ between the two viruses. Notably, M-SIV demonstrated greater infectivity than T-SIV, even when accounting for Env incorporation, suggesting that host cell-dependent factors influence infectivity. Further, M-SIV was more efficiently disseminated by HIV binding cellular lectins. We also evaluated the influence of cell type-dependent differences on SIV's vulnerability to carbohydrate binding agents (CBAs) and neutralizing antibodies. T-SIV demonstrated greater susceptibility to mannose-specific CBAs, possibly due to its elevated expression of oligomannose-type N-glycans. In contrast, M-SIV exhibited higher susceptibility to neutralizing sera in comparison to T-SIV. These findings underscore the importance of host cell-dependent attributes of SIV, such as glycosylation, in shaping both infectivity and the potential effectiveness of intervention strategies. Author summary: The human immunodeficiency virus (HIV) is the causative agent of the acquired immunodeficiency syndrome (AIDS), a lethal condition that necessitates life-long antiretroviral therapy for prevention. The envelope protein (Env) of HIV mediates the viral entry into host cells and is the sole target for the immune system on the surface of the virus. Env's extensive modification with sugars, so called N-glycans, shields crucial epitopes from neutralizing antibodies. Interestingly, key HIV producing cell types, such as CD4+ T cells and macrophages, modify Env with distinct N-glycosylation patterns. However, the specific molecular disparities in N-glycosylation between viruses from these cell types are unexplored, and whether the producer cell type impacts the viral spread and resistance to neutralization is incompletely understood. Utilizing the simian immunodeficiency virus (SIV) as a model for HIV, our study revealed differing N-glycan profiles between SIV Env produced in CD4+ T cells (T-SIV) and macrophages (M-SIV), with T-SIV incorporating more N-glycans of the oligomannose-type into Env than M-SIV. M-SIV displayed enhanced infectivity and transmissibility in in vitro studies. Additionally, M-SIV exhibited greater susceptibility to neutralizing sera compared to T-SIV, while T-SIV showed heightened susceptibility to mannose-specific carbohydrate-binding agents. These findings emphasize the critical role of host cell-dependent attributes in shaping N-glycosylation of Env as well as viral infectivity and spread. These findings have important implications for the development of new biomedical interventions against HIV. [ABSTRACT FROM AUTHOR]

The value of urinary neopterin as a predictive marker for disease progression in SIV- and HIV-2-infected rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis) was assessed by comparing pre- with postinfection data. Before infection stable baselines for neopterin were observed in both species with significantly higher concentrations in cynomolgus macaques than in rhesus macaques. After infection of cynomolgus macaques with human immunodeficiency virus type 2 (HIV-2) neopterin concentrations exceeded 1.2 - 4.2 times preinfection values, whereas rhesus monkeys infected with simian immunodeficiency virus (SIV) yielded concentrations of more than 8 times above baseline. Increased neopterin concentrations always preceded seroconversion. No rise of neopterin was observed in cynomolgus macaques remaining seronegative after inoculation with HIV-2, whereas after inoculation with SIV neopterin was slightly elevated in rhesus monkeys despite remaining seronegative. In animals with high virus replication a pronounced increase of neopterin levels was followed by signs of immunodeficiency. Therefore like in HIV-1-infected man, in macaques infected with SIV or HIV-2 the urinary neopterin concentration is an early and reliably predictive marker for AIDS disease progression and reflects pathogenicity. This parameter can be easily assessed in study protocols for drug and vaccine tests in monkeys as in man.

A two-stage genome-wide association study (GWAS) investigates whether any variation in the X chromosome is associated with the rate of progression to AIDS in HIV-1-infected women. Results reveal that SNP rs5968255 variation located at human Xq21.1 chromosome is a significant genetic determinant associated with the slow progression to AIDS in HIV-1-infected women.