Potent human monoclonal antibodies targeting Epstein-Barr virus gp42 reveal vulnerable sites for virus infection.

Epstein-Barr virus (EBV) is linked to various malignancies and autoimmune diseases, posing a significant global health challenge due to the lack of specific treatments or vaccines. Despite its crucial role in EBV infection in B cells, the mechanisms of the glycoprotein gp42 remain elusive. In this study, we construct an antibody phage library from 100 EBV-positive individuals, leading to the identification of two human monoclonal antibodies, 2B7 and 2C1. These antibodies effectively neutralize EBV infection in vitro and in vivo while preserving gp42's interaction with the human leukocyte antigen class II (HLA-II) receptor. Structural analysis unveils their distinct binding epitopes on gp42, different from the HLA-II binding site. Furthermore, both 2B7 and 2C1 demonstrate potent neutralization of EBV infection in HLA-II-positive epithelial cells, expanding our understanding of gp42's role. Overall, this study introduces two human anti-gp42 antibodies with potential implications for developing EBV vaccines targeting gp42 epitopes, addressing a critical gap in EBV research.

A gB nanoparticle vaccine elicits a protective neutralizing antibody response against EBV.

Epstein-Barr virus (EBV) is a global public health concern, as it is known to cause multiple diseases while also being etiologically associated with a wide range of epithelial and lymphoid malignancies. Currently, there is no available prophylactic vaccine against EBV. gB is the EBV fusion protein that mediates viral membrane fusion and participates in host recognition, making it critical for EBV infection in both B cells and epithelial cells. Here, we present a gB nanoparticle, gB-I53-50 NP, that displays multiple copies of gB. Compared with the gB trimer, gB-I53-50 NP shows improved structural integrity and stability, as well as enhanced immunogenicity in mice and non-human primate (NHP) preclinical models. Immunization and passive transfer demonstrate a robust and durable protective antibody response that protects humanized mice against lethal EBV challenge. This vaccine candidate demonstrates significant potential in preventing EBV infection, providing a possible platform for developing prophylactic vaccines for EBV.

Induction of Broadly Cross-Reactive Antibody Responses to SARS-CoV-2 Variants by S1 Nanoparticle Vaccines.

Despite the rapid deployment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, the emergence of SARS-CoV-2 variants and reports of their immune evasion characteristics have led to an urgent need for novel vaccines that confer potent cross-protective immunity. In this study, we constructed three different SARS-CoV-2 spike S1-conjugated nanoparticle vaccine candidates that exhibited high structural homogeneity and stability. Notably, these vaccines elicited up to 50-times-higher neutralizing antibody titers than the S1 monomer in mice. Crucially, it was found that the S1-conjugated nanoparticle vaccine could elicit comparable levels of neutralizing antibodies against wild-type or emerging variant SARS-CoV-2, with cross-reactivity to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), the effect of which could be further enhanced using our designed nanoparticles. Our results indicate that the S1-conjugated nanoparticles are promising vaccine candidates with the potential to elicit potent and cross-reactive immunity against not only wild-type SARS-CoV-2, but also its variants of concern, variants of interest, and even other pathogenic betacoronaviruses. IMPORTANCE The emergence of SARS-CoV-2 variants led to an urgent demand for a broadly effective vaccine against the threat of variant infection. The spike protein S1-based nanoparticle designed in our study could elicit a comprehensive humoral response toward different SARS-CoV-2 variants of concern and variants of interest and will be helpful to combat COVID-19 globally.

Second-order nonlinear optical responses of carboranyl-substituted indole/indoline derivatives: impact of different substituents.

Carborane has been the subject of great interest over the last decades due to its high structural, chemical, biological stability and diverse applications. In the present work, carboranyl-substituted indole/indoline compounds and their functionalized derivatives have been systematically investigated by density functional theory (DFT) method with the view of assessing their electronic structures and first hyperpolarizabilities. Significantly, the first hyperpolarizabilities can be obviously enhanced by the introduction of a strong electron-withdrawing group for closed-ring forms, while the strong electron-donating group is beneficial for large first hyperpolarizabilities for open-ring forms. It indicates that the NLO properties of these compounds can be enhanced by controlling their relative substituent groups. Furthermore, the time-dependent DFT calculation illustrates that the enhancement of the first hyperpolarizabilities are found due to the obvious charge transfer (CT) transition, and closed-ring forms have a significant difference on the CT patterns versus open-ring ones. Investigation of the structure-property relationship and substituent effects at the molecular level can benefit for further exploration of carboranyl-substituted indole/indoline derivatives with versatile and fascinating NLO properties.

Ion-π interaction in impacting the nonlinear optical properties of ion-buckybowl complexes.

Ion-buckybowl complexes have received considerable attention in modern chemical research due to its fundamental and practical importance. Herein, we performed density functional theory (DFT) to calculate the geometical structure, binding interactions, dipole moments and the first hyperpolarizabilities (ßtot) of ion-buckybowl complexes (ions are Cl(-) and Na(+), buckybowls are quadrannulene, corannulene and sumanene). It is found that the stabilities of ion-buckybowl compounds primarily originate from the interaction energy, which was proved by a new isomerization energy decomposition analysis approach. Plots of reduced density gradient mirror the ion-π weak interaction has been formed between the ions and buckybowls. Significantly, the buckybowl subunits cannot effectively impact the nonlinear optical (NLO), but the kind of ion has marked influence on the second-order NLO responses. The ßtot values of Cl(-)-buckybowl complexes are all larger as compared to that of Na(+)-buckybowl complexes, which is attributed to the large charge-transfer (CT) from Cl(-) to buckybowl. Our present work will be beneficial for further theoretical and experimental studies on the NLO properties of ion-buckybowl compounds.

Carborane tuning on iridium complexes: redox-switchable second-order NLO responses.

Much effort has been devoted to investigating the molecular geometries, electronic structures, redox properties and nonlinear optical (NLO) properties of Ir complexes involving o-, m- or p-carborane groups by density functional theory (DFT) methods. Switchable second-order NLO properties were induced by redox processes involving these complexes, and it was found that mainly the coordination bonds of Ir complexes changed during the oxidation process. Our calculations revealed that oxidation reactions have a significant influence on the second-order NLO response owing to the change in charge transfer pattern. The ß tot values of oxidized species are at least ∼9 times larger for set I and ∼5 times larger for set II than those of the corresponding parent complexes. Introduction of carborane groups into ppy (phenylpyridine) ligands can enhance the second-order NLO response by 1.2- 1.6 times by a metal-to-ligand charge transfer (MLCT) transition between the Ir atom and carborane. The ß tot of complex 2 [(ppy)2Ir(phen)](+) (phen = phenanthroline) is 3.3 times larger than that of complex 1 (ppy)2Ir(acce) (acce = acetylacetonate), which is caused by ligand-to-ligand charge transfer (LLCT) between ppy ligands and the ancillary ligand. Therefore, it can be concluded that the second-order NLO response can be effectively enhanced by oxidation reactions.