Decreased CD4 T cell counts drive aberrant B cell repertoire alterations in people living with HIV.

Understanding the evolution of broadly neutralizing antibody (bNAb) activity in people living with HIV is crucial for vaccine design and immunization strategies. It has been proposed that antibody cross-reactive activity is associated with lower CD4 T cell counts during people living with HIV, but the underlying mechanisms remain unclear. To further explore the correlation between antibody reactivity and CD4 T cell counts, we recruited people living with HIV with varying CD4 T cell counts: (i) CD4 T cell ≤50 cells/μL, (ii) 50 cells/μL < CD4 T cell ≤200 cells/μL, (iii) 200 cells/μL < CD4 T cell ≤500 cells/μL, (iv) 500 cells/μL < CD4 T cell.

Impact of CD4+ T cell and TCR repertoires on SARS-CoV-2-Specific antibody responses in PLWH following COVID-19 vaccination.

In people living with human immunodeficiency virus (HIV, PLWH), the coronavirus disease 2019 (COVID-19) vaccine often results in a limited humoral immune response. While a reduced absolute CD4+ T cell count is a known factor, other determinants remain unclear. To investigate variables influencing the differential antibody response to the COVID-19 vaccine in PLWH, 43 HIV-1/AIDS patients receiving antiretroviral therapy (ART) and 2 doses of the COVID-19 vaccine were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulin G (IgG) levels and neutralizing antibody (NAb) titers.

Advances in Mechanism of HIV-1 Immune Reconstitution Failure: Understanding Lymphocyte Subpopulations and Interventions for Immunological Nonresponders.

In individuals diagnosed with AIDS, the primary method of sustained suppression of HIV-1 replication is antiretroviral therapy, which systematically increases CD4+ T cell levels and restores immune function. However, there is still a subset of 10-40% of people living with HIV who not only fail to reach normal CD4+ T cell counts but also experience severe immune dysfunction. These individuals are referred to as immunological nonresponders (INRs).

Are the original SARS-CoV-2 novel mutants from in vitro culture able to escape the immune response?

Monitoring variations in the virus genome to understand the SARS-CoV-2 evolution and spread of the virus is extremely important. Seven early SARS-CoV-2 isolates in China were cultured in vitro and were analyzed for their viral infectivity through viral growth assay, tissue culture infectious dose (TCID ) assay, spike protein quantification, and next generation sequencing analysis, and the resultant mutations in spike protein were used to generate the corresponding pseudoviruses for analysis of immune escape from vaccination and postinfection immunity. The results revealed that in vitro cultured SARS-CoV-2 virus had much higher mutation frequency (up to ~20 times) than that in infected patients, suggesting that SARS-CoV-2 diversify under favorable conditions.

Two Resveratrol Oligomers Inhibit Cathepsin L Activity to Suppress SARS-CoV-2 Entry.

Cell entry of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) depends on specific host cell proteases, which are the key targets for preventing and treating viral infections. Herein, we describe miyabenol C and trans-ε-viniferin, two resveratrol oligomers that specifically inhibit SARS-CoV-2 entry by targeting host protease cathepsin L. Several cell-based assays were used to demonstrate the effect of resveratrol oligomers, and their target was identified via screening of antiviral targets.

Evaluation of humoral immune responses induced by different SARS-CoV-2 spike trimers from wild-type and emerging variants with individual, sequential, and combinational delivered strategies.

The spike trimer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an effective target for inducing neutralizing antibodies by coronavirus disease 2019 (COVID-19) vaccines. However, the diversity of spike protein from emerging SASR-CoV-2 variants has become the major challenge for development of a universal vaccine. To investigate the immunogenicity of spike proteins from various circulating strains including wild type, Delta, and Omicron variants, we produced various natural spike trimers and designed three vaccination strategies, that is, individual, sequential, and bivalent regimens to assess autologous and heterogenous antibody responses in a mouse model.

Novel Monoclonal Antibodies and Recombined Antibodies Against Variant SARS-CoV-2.

The mutants resulted from the ongoing SARS-CoV-2 epidemic have showed resistance to antibody neutralization and vaccine-induced immune response. The present study isolated and identified two novel SARS-CoV-2 neutralizing antibodies (nAbs) from convalescent COVID-19 patients. These two nAbs (XG81 and XG83) were then systemically compared with nine nAbs that were reconstructed by using published data, and revealed that, even though these two nAbs shared targeting epitopes on spike protein, they were different from any of the nine nAbs.

Crucial Mutations of Spike Protein on SARS-CoV-2 Evolved to Variant Strains Escaping Neutralization of Convalescent Plasmas and RBD-Specific Monoclonal Antibodies.

Small number of SARS-CoV-2 epidemic lineages did not efficiently exhibit a neutralization profile, while single amino acid mutation in the spike protein has not been confirmed in altering viral antigenicity resulting in immune escape. To identify crucial mutations in spike protein that escape humoral immune response, we evaluated the cross-neutralization of convalescent plasmas and RBD-specific monoclonal antibodies (mAbs) against various spike protein-based pseudoviruses. Three of 24 SARS-CoV-2 pseudoviruses containing different mutations in spike protein, including D614G, A475V, and E484Q, consistently showed an altered sensitivity to neutralization by convalescent plasmas.

Employing Broadly Neutralizing Antibodies as a Human Immunodeficiency Virus Prophylactic & Therapeutic Application.

Despite the discovery that the human immunodeficiency virus 1 (HIV-1) is the pathogen of acquired immunodeficiency syndrome (AIDS) in 1983, there is still no effective anti-HIV-1 vaccine. The major obstacle to the development of HIV-1 vaccine is the extreme diversity of viral genome sequences. Nonetheless, a number of broadly neutralizing antibodies (bNAbs) against HIV-1 have been made and identified in this area.

Digital PCR assay for the effective detection of COVID-19 patients with SARS-CoV-2 low viral load.

Objective: Viral nucleic acid detection by real-time reverse transcription polymerase chain reaction (qPCR) is the current standard method for diagnosis of SARS-CoV-2 infection. However, due to low viral load in some COVID-19 patients, false negative results from this method have been repeatedly reported.

Method: In this study, we compared the sensitivity and specificity of digital PCR (dPCR) in simulated samples and clinical samples with qPCR assay through a series of vigorous tests.

A colorimetric immunoassay for determination of Escherichia coli O157:H7 based on oxidase-like activity of cobalt-based zeolitic imidazolate framework.

Cobalt-based zeolitic imidazolate framework nanosheets (ZIF-67) with oxidase-like catalytic activities as an immunoprobe were employed to enhance the sensitivity of an immunoassay. ZIF-67 was synthesized via the solvothermal method using 2-methylimidazole and cobalt dichloride as substrates. A colorimetric immunoassay for Escherichia coli (E.

Biochemical characterization of SARS-CoV-2 nucleocapsid protein.

The nucleocapsid (N) protein is an important antigen for coronavirus, which participate in RNA package and virus particle release. In this study, we expressed the N protein of SARS-CoV-2 and characterized its biochemical properties. Static light scattering, size exclusive chromatography, and small-angle X-ray scattering (SAXS) showed that the purified N protein is largely a dimer in solution.

Characteristics of patients with coronavirus disease (COVID-19) confirmed using an IgM-IgG antibody test.

Coronavirus disease (COVID-19), caused by a novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly developed into a pandemic since it was first reported in December 2019. Nucleic acid testing is the standard method for the diagnosis of viral infections. However, this method reportedly has a low positivity rate.

Advances in Developing CAR T-Cell Therapy for HIV Cure.

Acquired immune deficiency syndrome (AIDS), which is caused by HIV infection, is an epidemic disease that has killed millions of people in the last several decades. Although combination antiretroviral therapy (cART) has enabled tremendous progress in suppressing HIV replication, it fails to eliminate HIV latently infected cells, and infected individuals remain HIV positive for life. Lifelong antiretroviral therapy is required to maintain control of virus replication, which may result in significant problems, including long-term toxicity, high cost, and stigma.

Attenuated as a Vaccine Vector for the Delivery of OMPW, the Outer Membrane Protein of .

(LM) is a gram-positive facultative intracellular pathogen that could stimulate host to produce inflammatory response, cell-mediated immunity, and humoral immunity. In this study, an attenuated live vector vaccine for (AH) named was successfully constructed using an attenuated vector named , in which , , A, and B genes were deleted from wild-type LM. To construct , a recombinant plasmid pERL3-dat-ompW obtained by inserting the gene from and outer membrane protein gene W from AH into pERL3 plasmid was transformed into cell.

Attenuated Listeria monocytogenes protecting zebrafish (Danio rerio) against Vibrio species challenge.

Live attenuated bacteria is a promising candidate vector for the delivery of vaccines in clinic trials. In the field of aquaculture industry, live vector vaccine also could provide long-term and effective protection against fish bacterial diseases. In our previous work, we demonstrated attenuated Listeria monocytogenes (Lm) had the potential to be an aquaculture vaccine vector in cellular level and zebrafish model.

Reactive oxygen species inhibit biofilm formation of Listeria monocytogenes.

Although the level of reactive oxygen species (ROS) is altered upon the formation of bacterial biofilm, the relationship between ROS alteration and biofilm formation is still unclear. The aim of the present study is to use Listeria monocytogenes (L. monocytogenes) as a model organism to examine whether ROS have an effect on the biofilm formation.

Development of a Bacterial Macroarray for the Rapid Screening of Targeted Antibody-Secreted Hybridomas.

Hybridoma screening is a key step for the successful generation of high-affinity analyte-specific monoclonal antibodies (MAbs). This work presents an innovative screening method, known as a bacterial macroarray, generated by contact printing of hybridoma cell supernatant samples on a nitrocellulose (NC) membrane initially coated with fluorescein isothiocyanate (FITC)-labeled bacteria. Given that bacterial fixation will be influenced by complex bacterial surface structures, we selected both gram-positive bacteria ( Staphylococcus aureus and Listeria monocytogenes) and gram-negative bacteria ( Escherichia coli O157:H7 and Cronobacter sakazakii) to optimize the fixation conditions for binding to the NC membrane, such as the aperture of the NC membrane, the concentration of bacteria, the dosage of glycerin in the spotting buffer, and the fixation time and temperature.

Gut Microbiota and Relevant Metabolites Analysis in Alcohol Dependent Mice.

Alcohol abuse is a major public health crisis. Relative evidences supported that the gut microbiota (GM) played an important role in central nervous system (CNS) function, and the composition of them had changed after alcohol drinking. We sought to explore the changes of GM in alcohol dependence.

Exploration of the bacterial invasion capacity of Listeria monocytogenes in ZF4 cells.

Despite the results from zebrafish challenged model have demonstrated that Listeria monocytogenes (Lm) has strong adjuvant effects when this attenuated pathogenic bacteria is viewed as aquaculture vaccine vector, the underlying mechanism is not clear and extensive investigations are required. To further explore the potential of Lm in the field of aquaculture vaccine, zebrafish embryonic fibroblast cell line (ZF4) was used to evaluate the invasion ability of Lm. The data from cellular level showed that Lm had the lower invasion tendentiousness in ZF4 cells while bacterial invasion capacity was compared between zebrafish embryos cell line and human intestinal epithelial cell line.

Evaluation of Caco-2 cells response to Listeria monocytogenes virulence factors by RT-PCR.

Listeria monocytogenes expresses various virulence factors enabling the invasion and multiplying in host cells, and together induces cytokines transcription. In order to explore the relationship between virulence factors of L. monocytogenes wild-type EGD-e and cellular response in human colonic epithelial cell line(Caco-2), we constructed mutant strains with in-frame deletions of critical virulence genes of inlA, inlB, hly, actA and virulence regulatory factor prfA from EGD-e, respectively.

Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.

Live bacteria, including attenuated bacteria and probiotics, can be engineered to deliver target antigen to excite the host immune system. The preponderance of these live bacterial vaccine vectors is that they can stimulate durable humoral and cellular immunity. Moreover, delivery strategies of heterologous antigen in live bacterial promote the applications of new vaccine development.