Loss of HIV candidate vaccine efficacy in male macaques by mucosal nanoparticle immunization rescued by V2-specific response.

Systemic vaccination of macaques with V1-deleted (ΔV1) envelope immunogens reduce the risk of SIV acquisition by approximately 60%, with protective roles played by V2-specific ADCC and envelope-specific mucosal IL-17NKp44 innate lymphoid cells (ILCs). We investigated whether increased mucosal responses to V2 benefit vaccine efficacy by delivering oral nanoparticles (NPs) that release V2-scaffolded on Typhoid Toxin B (TTB) to the large intestine. Strikingly, mucosal immunization of male macaques abrogated vaccine efficacy with control TTB or empty NPs, but vaccine efficacy of up to 47.

CL-705G: a novel chemical Kir6.2-specific K channel opener.

K channels have diverse roles, including regulation of insulin secretion and blood flow, and protection against biological stress responses and are excellent therapeutic targets. Different subclasses of K channels exist in various tissue types due to the unique assemblies of specific pore-forming (Kir6.x) and accessory (SURx) subunits.

Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIV acquisition in macaques.

Introduction: An efficacious HIV vaccine will need to elicit a complex package of innate, humoral, and cellular immune responses. This complex package of responses to vaccine candidates has been studied and yielded important results, yet it has been a recurring challenge to determine the magnitude and protective effect of specific immune responses in isolation. We therefore designed a single, viral-spike-apical, epitope-focused V2 loop immunogen to reveal individual vaccine-elicited immune factors that contribute to protection against HIV/SIV.

Effect of Passive Administration of Monoclonal Antibodies Recognizing Simian Immunodeficiency Virus (SIV) V2 in CH59-Like Coil/Helical or β-Sheet Conformations on Time of SIV Acquisition.

The monoclonal antibodies (MAbs) NCI05 and NCI09, isolated from a vaccinated macaque that was protected from multiple simian immunodeficiency virus (SIV) challenges, both target an overlapping, conformationally dynamic epitope in SIV envelope variable region 2 (V2). Here, we show that NCI05 recognizes a CH59-like coil/helical epitope, whereas NCI09 recognizes a β-hairpin linear epitope. , NCI05 and, to a lesser extent, NCI09 mediate the killing of SIV-infected cells in a CD4-dependent manner.

Conformational change of the response regulator BvgA accompanies its activation of the virulence gene .

The BvgAS two-component system regulates virulence gene expression in . Although precise three-dimensional structural information is not available for the response regulator BvgA, its sequence conservation with NarL and previous studies have indicated that it is composed of 3 domains: an -terminal domain (NTD) containing the phosphorylation site, a linker, and a DNA-binding C-terminal domain (CTD). Previous work has determined how BvgA dimers interact with the promoter (P ) of , the gene encoding the virulence adhesin filamentous hemagglutinin.

Corrigendum to "Triazolo[4,5-]pyrimidines as validated general control nonderepressible 2 (GCN2) protein kinase inhibitors reduce growth of leukemia cells" [Comput. Struct. Biotechnol. J. 16 (2018) 350-360].

[This corrects the article DOI: 10.1016/j.csbj.

SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate.

Aim: The COVID-19 pandemic is caused by infection with the SARS-CoV-2 virus. The major mutation detected to date in the SARS-CoV-2 viral envelope spike protein, which is responsible for virus attachment to the host and is also the main target for host antibodies, is a mutation of an aspartate (D) at position 614 found frequently in Chinese strains to a glycine (G). We sought to infer health impact of this mutation.