Protection of Omicron Bivalent Vaccine, Previous Infection, and Their Induced Neutralizing Antibodies Against Symptomatic Infection With Omicron XBB.1.16 and EG.5.1.

Background: Data are limited on the protective role of the Omicron BA bivalent vaccine, previous infection, and their induced neutralizing antibodies against Omicron XBB.1.16 and EG.

Discovery of Potent DAG-Lactone Derivatives as HIV Latency Reversing Agents.

Toward human immunodeficiency virus type-1 (HIV-1) cure, cells latently infected with HIV-1 must be eliminated from people living with HIV-1. We previously developed a protein kinase C (PKC) activator, diacylglycerol (DAG)-lactone derivative , with high HIV-1 latency-reversing activity, based on YSE028 () as a lead compound and found that the activity was correlated with binding affinity for PKC and stability against esterase-mediated hydrolysis. Here, we synthesized new DAG-lactone derivatives not only containing a tertiary ester group or an isoxazole surrogate but also several symmetric alkylidene moieties to improve HIV-1 latency reversing activity.

HIV Reservoirs and Treatment Strategies toward Curing HIV Infection.

Combination antiretroviral therapy (cART) has significantly improved the prognosis of individuals living with human immunodeficiency virus (HIV). Acquired immunodeficiency syndrome has transformed from a fatal disease to a treatable chronic infection. Currently, effective and safe anti-HIV drugs are available.

Mutual generation in neuronal activity across the brain via deep neural approach, and its network interpretation.

In the brain, many regions work in a network-like association, yet it is not known how durable these associations are in terms of activity and could survive without structural connections. To assess the association or similarity between brain regions with a generating approach, this study evaluated the similarity of activities of neurons within each region after disconnecting between regions. The "generation" approach here refers to using a multi-layer LSTM (Long Short-Term Memory) model to learn the rules of activity generation in one region and then apply that knowledge to generate activity in other regions.

Whole-Brain Evaluation of Cortical Microconnectomes.

The brain is an organ that functions as a network of many elements connected in a nonuniform manner. In the brain, the neocortex is evolutionarily newest and is thought to be primarily responsible for the high intelligence of mammals. In the mature mammalian brain, all cortical regions are expected to have some degree of homology, but have some variations of local circuits to achieve specific functions performed by individual regions.

Preinfection Neutralizing Antibodies, Omicron BA.5 Breakthrough Infection, and Long COVID: A Propensity Score-Matched Analysis.

Background: Data are limited on the role of preinfection humoral immunity protection against Omicron BA.5 infection and long coronavirus disease (COVID) development.

Methods: We conducted nested case-control analysis among tertiary hospital staff in Tokyo who donated blood samples in June 2022 (1 month before Omicron BA.

Synthesis and evaluation of DAG-lactone derivatives with HIV-1 latency reversing activity.

Cells latently infected with human immunodeficiency virus type 1 (HIV-1) prevent people living with HIV-1 from obtaining a cure to the infectious disease. Latency reversing agents (LRAs) such as protein kinase C (PKC) activators and histone deacetylase (HDAC) inhibitors can reactivate cells latently infected with HIV-1. Several trials based on treatment with HDAC inhibitors alone, however, failed to reduce the number of latent HIV-1 reservoirs.

Omicron BA.1 neutralizing antibody response following Delta breakthrough infection compared with booster vaccination of BNT162b2.

Background: Longitudinal data are lacking to compare booster effects of Delta breakthrough infection versus third vaccine dose on neutralizing antibodies (NAb) against Omicron.

Methods: Participants were the staff of a national research and medical institution in Tokyo who attended serological surveys on June 2021 (baseline) and December 2021 (follow-up); in between, the Delta-dominant epidemic occurred. Of 844 participants who were infection-naïve and had received two doses of BNT162b2 at baseline, we identified 11 breakthrough infections during follow-up.

Immunogenicity and safety of single booster dose of KD-414 inactivated COVID-19 vaccine in adults: An open-label, single-center, non-randomized, controlled study in Japan.

Although vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) induce effective immune responses, vaccination with booster doses is necessary because of waning immunity. We conducted an open-label, non-randomized, single-arm study in adults in Japan to assess the immunogenicity and safety of a single booster dose of the KD-414 purified whole-SARS-CoV-2-virion inactivated vaccine candidate after vaccination with a primary series of BNT162b2. The primary endpoint was serum neutralizing activity at 7 days after booster injection compared with the primary series of BNT162b2.

Neutralizing antibodies after three doses of the BNT162b2 vaccine, breakthrough infection, and symptoms during the Omicron-predominant wave.

Objectives: To investigate the role of immunogenicity after the third vaccine dose against Omicron infection and COVID-19-compatible symptoms of infection.

Methods: First, we examined vaccine effectiveness (VE) of the third dose against the second dose during the Omicron wave among the staff at a tertiary hospital in Tokyo. In a case-control study of third vaccine recipients, we compared the preinfection live-virus neutralizing antibodies (NAb) against Omicron between breakthrough cases and their controls who had close contact with patients with COVID-19.

4-phenylquinoline-8-amine induces HIV-1 reactivation and apoptosis in latently HIV-1 infected cells.

Combinational antiretroviral therapy (cART) dramatically suppresses the viral load to undetectable levels in human immunodeficiency virus (HIV)-infected patients. However, HIV-1 reservoirs in CD4+T cells and myeloid cells, which can evade cART and host antiviral immune systems, are still significant obstacles to HIV-1 eradication. The "Shock and Kill" approach using latently-reversing agents (LRAs) is therefore currently developing strategies for effective HIV-1 reactivation from latency and inducing cell death.

Dihydroceramide Δ4-Desaturase 1 Is Not Involved in SARS-CoV-2 Infection.

Dihydroceramide Δ4-desaturase 1 (DEGS1) enzymatic activity is inhibited with N-(4-hydroxyphenyl)-retinamide (4-HPR). We reported previously that 4-HPR suppresses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry through a DEGS1-independent mechanism. However, it remains unclear whether DEGS1 is involved in other SARS-CoV-2 infection processes, such as virus replication and release.

SARS-CoV-2 specific T cell and humoral immune responses upon vaccination with BNT162b2: a 9 months longitudinal study.

The humoral and cellular immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon the coronavirus disease 2019 (COVID-19) vaccination remain to be clarified. Hence, we aimed to investigate the long-term chronological changes in SARS-CoV-2 specific IgG antibody, neutralizing antibody, and T cell responses during and after receiving the BNT162b2 vaccine. We performed serological, neutralization, and T cell assays among 100 hospital workers aged 22-73 years who received the vaccine.

A widely distributed HIV-1 provirus elimination assay to evaluate latency-reversing agents .

Persistence of HIV-1 latent reservoir cells during antiretroviral therapy (ART) is a major obstacle for curing HIV-1. Even though latency-reversing agents (LRAs) are under development to reactivate and eradicate latently infected cells, there are few useful models for evaluating LRA activity . Here, we establish a long-term cell culture system called the "widely distributed intact provirus elimination" (WIPE) assay.

An Association Study of HLA with the Kinetics of SARS-CoV-2 Spike Specific IgG Antibody Responses to BNT162b2 mRNA Vaccine.

BNT162b2, an mRNA-based SARS-CoV-2 vaccine (Pfizer-BioNTech, New York, NY, USA), is one of the most effective COVID-19 vaccines and has been approved by more than 130 countries worldwide. However, several studies have reported that the COVID-19 vaccine shows high interpersonal variability in terms of humoral and cellular responses, such as those with respect to SARS-CoV-2 spike protein immunoglobulin (Ig)G, IgA, IgM, neutralizing antibodies, and CD4 and CD8 T cells. The objective of this study is to investigate the kinetic changes in anti-SARS-CoV-2 spike IgG (IgG-S) profiles and adverse reactions and their associations with HLA profiles (, , , , , , and ) among 100 hospital workers from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan.

Coronavirus Disease 2019 (COVID-19) Breakthrough Infection and Post-Vaccination Neutralizing Antibodies Among Healthcare Workers in a Referral Hospital in Tokyo: A Case-Control Matching Study.

Background: While increasing coverage of effective vaccines against coronavirus disease 2019 (COVID-19), emergent variants raise concerns about breakthrough infection. Data are limited, however, whether breakthrough infection during the epidemic of the variant is ascribed to insufficient vaccine-induced immunogenicity.

Methods: We describe incident COVID-19 in relation to the vaccination program among workers of a referral hospital in Tokyo.

Consistency of the results of rapid serological tests for SARS-CoV-2 among healthcare workers in a large national hospital in Tokyo, Japan.

We assessed the consistency of seropositive results of three rapid immunoassays (Kits A, B, and C) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared to highly accurate serological tests (Abbott and Roche) among healthcare workers in a hospital in Tokyo. The seroprevalence of SARS-CoV-2 immunoglobulin G was 0.41%, 2.

A Therapeutic Strategy to Combat HIV-1 Latently Infected Cells With a Combination of Latency-Reversing Agents Containing DAG-Lactone PKC Activators.

Advances in antiviral therapy have dramatically improved the therapeutic effects on HIV type 1 (HIV-1) infection. However, even with potent combined antiretroviral therapy, HIV-1 latently infected cells cannot be fully eradicated. Latency-reversing agents (LRAs) are considered a potential tool for eliminating such cells; however, recent and studies have raised serious concerns regarding the efficacy and safety of the "shock and kill" strategy using LRAs.

Neutralization of SARS-CoV-2 with IgG from COVID-19-convalescent plasma.

While there are various attempts to administer COVID-19-convalescent plasmas to SARS-CoV-2-infected patients, neither appropriate approach nor clinical utility has been established. We examined the presence and temporal changes of the neutralizing activity of IgG fractions from 43 COVID-19-convalescent plasmas using cell-based assays with multiple endpoints. IgG fractions from 27 cases (62.

A novel highly quantitative and reproducible assay for the detection of anti-SARS-CoV-2 IgG and IgM antibodies.

The quantitative range and reproducibility of current serological tests for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are not optimized. Herein, we developed a diagnostic test that detects SARS-CoV-2 IgG and IgM with high quantitativeness and reproducibility and low interference. The system was based on the high-sensitivity chemiluminescence enzyme immunoassay (HISCL) platform and detects IgG and IgM specific to SARS-CoV-2 spike and nucleocapsid proteins.