Volume 229, Issue 5, 15 May 2024

In this pilot study in people with HIV, a single infusion of haploidentical related donor NK cells supported by either IL-2 or N-803 (an IL-15 superagonist) was well tolerated and resulted in decreased frequency of HIV-producing cells in lymph nodes.

Among virally suppressed PWH, SSRIs were associated with reduced neurodegeneration and lower immune activation, SNRIs with higher levels of myeloid and lymphoid activation, while ACEIs and statins had no distinct biomarker signatures. Specific comedications may affect HIV-related persistent immune activation.

IL-32, a proinflammatory cytokine upregulated in HIV infection, induces the generation of CD4 T cells with cardiotropic phenotype. Analysis from people with HIV show that these cells are enriched with HIV DNA suggesting a potential role for IL-32 in heart inflammation.

Lenacapavir is a first-in-class capsid inhibitor that acts at multiple steps in the HIV-1 replication cycle. Our findings show that lenacapavir is active against HIV-2 isolates and drug-resistant HIV-2 mutants in culture, albeit with reduced potency relative to HIV-1.

RNA profiling of rigorously separated and characterized brain tissue-derived extracellular vesicles as well as source tissues from the simian immunodeficiency virus model of HIV disease reveal potential RNA regulatory networks associated with infection and CNS pathology.

Cannabis use in men with subtype C HIV-1 and suppressed viral load associates with reduced size and distribution of tissue reservoirs, lower viral DNA copies in those tissues, as well as reduced expression levels of proinflammatory cytokines IL-1β and IL-6.

We elucidated the diversity of circulating γδ T-cell subsets with new resolution. Our results reveal novel subsets within the Vδ1⁺ and Vδ2⁺ γδ T-cell factions and indicate selective alterations of subpopulations of Vδ1⁺ and Vδ2⁺ cells with ART-suppressed HIV infection.

Overall, a third mRNA vaccine improved serological responses among immunocompromised individuals and nonimmunocompromised HCW. SOT recipients and individuals with hematologic malignancies exhibit the poorest responses. T-cell responses appear more favorable in HCW.

Using phage display to map antibody responses against SARS-CoV-2, we demonstrate that, despite globally decreased responses, kidney transplant recipients recognize similar spike epitopes as controls, suggesting antibody breadth is not the cause of decreased vaccine efficacy in this immunosuppressed group.

A mouse model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection demonstrates that the differential impact of SARS-CoV-2 variants on lung may be attributed to differential levels of viral proteins among airway, immune, and endothelial lung cells.

Kaposi sarcoma continues to cause substantial morbidity and mortality in at-risk populations in the southern United States. Among young minority men who have sex with men in Houston, Texas, the prevalence of Kaposi sarcoma–associated herpesvirus was 36.7% and the incidence was 8.9 per 100 person-years.

Despite similar antibody response, cell-based influenza vaccine induces a distinct transcriptomic response compared with egg-based vaccine. Cell-based influenza vaccination stimulates increased interferon-induced gene expression, which tracks with vaccine-induced seroconversion, regardless of vaccine type.

Human norovirus genotype–specific antibody levels measured in 3 assays were highly correlated. However, choice of antibody assay can affect assessments of vaccine immunogenicity; specifically, a bivalent GI.1/GII.4 vaccine associated with protection from GII.2-associated illness induced infrequent GII.2-specific neutralization responses.

Cytokine-expressing RNA-based adjuvants activated antigen-presenting cells and increased the proportion of polyclonal T cells when used in conjunction with an influenza vaccine while minimizing critical illness scores and weight loss in immunized mice.

Stimulating airway epithelia with interleukin 13 increased DPP4, the receptor for Middle East respiratory syndrome coronavirus (MERS-CoV). However, this failed to increase MERS-CoV infection, suggesting that elevated airway epithelial DPP4 cannot explain increased risk of severe MERS in chronic airway disease.

Replicating influenza A virus induces a robust interferon response in the human airway epithelium that interferes with SARS-CoV-2 in simultaneous and sequential infections, and both antiviral response and viral interference are reversed by targeting influenza replication with oseltamivir.

In the study, we used a CVA6-induced myocardial injury mouse model and neutrophil-depleted antibodies to investigate the pathophysiology of myocardial injury caused by CVA6. Our results showed that excessive neutrophils contribute to myocardial injury caused by CVA6 infection.

During 2 consecutive years with unchanged A(H3N2) vaccine strain, reduced antibody response was observed in older adults who received prior-year vaccination compared to those who did not, regardless of receiving standard-dose or enhanced influenza vaccines in the current year.

We conducted a meta-analysis of published rotavirus genotype data. After accounting for natural regional and temporal variation, there was no substantial evidence of long-term, vaccine-related selective pressures on circulating genotypes. Increased G2P[4] prevalence may be transient after rotavirus vaccine introduction.

We performed a systematic review and meta-analysis of studies of rotavirus in Africa and found high prevalences in human, animal, and environmental water sources, underscoring the need for a One Health approach to limiting the spread of this disease.

Whole-genome sequencing (WGS) accurately identifies isoniazid and rifampicin resistance. For most drugs, positive WGS results are reliable to predict phenotypic drug sensitivity. Noncatalog-based approach does not improve the predictive value for phenotypic antituberculosis drugs resistance compared to catalog-based approach.

We explore the potential utility and limitations of Mycobacterium tuberculosis whole-genome sequencing at a sentinel site in a high-incidence setting for assessing changes in transmission dynamics over time.

Presented are results from an open-label dose escalation human Bacillus Calmette-Guérin challenge study. The combined results indicate that this human challenge model is a feasible approach for assessing in vivo tuberculosis immunity and could facilitate the vaccine development process.

ATRA was found to modulate the immune response through ERK and p38 pathways to protect the host from Mycobacterium tuberculosis infection. Furthermore, combination therapy of ATRA and INH significantly increased the host resistance to tuberculosis.

New approaches are urgently needed for Clostridioides difficile infection. This study provides proof-of-concept for a nonantibiotic strategy against C. difficile by targeting cell survival pathway.

There is an urgent need for new nonantibiotic-based treatment strategies for Clostridioides difficile infection. C. difficile toxin B (TcdB) is a virulent factor that is essential for causing disease. Here, we investigated whether a survival-signaling pathway could protect against TcdB. We found significant increase in caspase-3 apoptotic activity in intestinal epithelial cells of mice exposed to TcdB. Subsequently, activation of the MIF-CD74-Akt prosurvival signaling pathway blocked TcdB-induced caspase-3 activity and intestinal epithelial cell death. This brief report provides proof-of-concept that targeting prosurvival pathways may represent a unique antibiotic-independent strategy for protecting against C. difficile toxin-mediated cell death.

Mycoplasma gallisepticum–produced extracellular vesicles (EVs) carry key virulence factors and influence macrophage activation, contributing to M. gallisepticum pathogenesis. Understanding EVs and their proteins sheds light on infection mechanisms and informs prevention strategies.

RNA sequencing performed with blood samples from patients with gram-positive or gram-negative bacteremia demonstrated reduced host transcriptional signatures involving mitochondrial energy transduction in methicillin-resistant versus methicillin-susceptible Staphylococcus aureus. Patients with gram-negative infection had increased activation of the classic complement system.

We demonstrated that 3 Escherichia coli strains involved in bone and joint infection (BJI) relapses adapted in patients through various molecular mechanisms, allowing them to outcompete other bacteria or evade the immune system. Understanding in-patient adaptation may help fight BJI relapses.

We assessed the unsupervised 14-day low-dose primaquine for preventing relapses in vivax malaria patients without screening for glucose-6-phosphate dehydrogenase deficiency in eastern Myanmar. One-year follow-ups revealed a cumulative recurrence rate of 9.1%, with all relapses occurring within the first 6 months.

PfGARP is an erythrocyte surface antigen encoded by Plasmodium falciparum, the causative agent of severe human malaria pathophysiology. We provide evidence for a mechanism that targets growth arrest of intraerythrocytic parasites by polyclonal antibodies against PfGARP via a novel PfGARP-independent pathway.

In India’s antimalarial resistance surveillance (2014–2015), Pfdhfr exhibited triple mutants (northeast), widespread Pfdhps wild types, and predominantly Pfmdr1 wild types (except northwest). Pfk13 had synonymous mutations (central). Resistance varied across clusters, with higher resistance in the northeast. Primaquine use likely contained drug resistance.

Tuberculosis treatment development could be accelerated with the use of adaptive platform trials, but efficient surrogates are needed for decision making. This systematic review summarizes the published evidence about biomarkers evaluated to predict outcomes relevant for tuberculosis clinical trials.