Expansion of genital Tregs reduces neutrophil influx and maintains mucosal barrier integrity during inflammatory bacteria challenge.

Genital inflammation is associated with increased HIV risk. We previously found that endocervical Tregs correlated with decreased genital inflammation and reduced HIV target cells. IL-2 induces Tregs, and efforts to potentiate its regulatory activities clinically are ongoing.

Circulating Short-Chain Fatty Acids: Association with Vaginal Microbiota, Genital Inflammation, and HIV Acquisition.

Little is known about the relationships between circulating short-chain fatty acids (SCFAs) and genital microbiota, inflammation, and the risk for HIV infection in women. As circulating SCFAs are potentially modifiable, for example, through dietary fiber or probiotics, we investigated association of circulating SCFA levels with these outcomes. We carried out a nested matched case-control study within a randomized trial of an antiretroviral microbicide to prevent HIV infection to study the association between circulating SCFAs and HIV acquisition (primary outcome for case definition), vaginal microbiota, and genital inflammation.

Integrin α4β7 as a predictor of HIV acquisition: one thread in a complex tapestry.

Cellular susceptibility to HIV is associated with integrin α4β7, a mucosal homing receptor involved with trafficking HIV target cells to sites of HIV replication. However, studies investigating preinfection α4β7 expression as a predictor of HIV outcomes have yielded inconsistent findings, raising questions about the role of α4β7 in HIV acquisition across populations. In this issue of the JCI, Machmach et al.

Improved antibody breadth with an extended primary dose interval of COVID-19 vaccine is overcome by boosters.

Introduction: During rollout of mRNA-based COVID-19 vaccines, several jurisdictions extended the interval between the first and second doses to prioritize wider population access to limited vaccine supply. This study evaluated the effects of an extended dose interval on development of antibody and cell-mediated responses following the primary dose series and a subsequent booster dose.

Methods: Blood samples were collected from mRNA COVID-19 vaccine recipients at baseline and longitudinally after each dose.

Pre-Human Immunodeficiency Virus (HIV) α4β7hi CD4+ T Cells and HIV Risk Among Heterosexual Individuals in Africa.

Background: CD4+ T cells expressing α4β7 are optimal targets for human immunodeficiency virus (HIV) infections, with higher pre-HIV α4β7hi expression linked to increased HIV acquisition and progression in South African women. However, similar associations were not observed in men who have sex with men or people who inject drugs in the Americas, indicating need for further research.

Methods: This retrospective case-control study enrolled heterosexual men and women from South Africa (HIV Vaccine Trials Network [HVTN] 503) and East Africa (Partners Preexposure Prophylaxis/Couples' Observational Study [PP/COS]), quantifying α4β7 expression on CD4+ T cells as a predictor of subsequent HIV risk using flow cytometry analyses.

A Population-Based Study of SARS-CoV-2 IgG Antibody Responses to Vaccination in Manitoba.

Understanding variables that influence antibody responses to COVID-19 vaccination within a population can provide valuable information on future vaccination strategies. In this population-based study, we examined the antibody responses to COVID-19 vaccination in Manitoba using residual serum specimens collected between January 2021 and March 2022 (n = 20,365). Samples were tested for spike and nucleocapsid IgG against SARS-CoV-2 using clinically validated assays.

Toward improving anal health care among GBMSM in Kenya: Lessons from a patient's illness, treatment and recovery journey.

We aimed to illuminate the challenges of treating anal diseases among gay, bisexual and other men who have sex with men (GBMSM) in a homophobic climate amid resource constraints. Building on a long-term Kenyan-Canadian collaboration, an anal healthcare intervention study, known as the WEMAH Project, was initiated in January 2022. The initial collaborative work strengthened existing anal health services provided at a community-based clinic serving GBMSM in Nairobi.

A cross-sectional survey exploring HIV and HCV prevalence among men who purchase sex in Dnipro, Ukraine.

Background: HIV programming in Ukraine largely targets "key population" groups. Men who purchase sex are not directly reached. The aim of our study was to explore the prevalence of sexually transmitted and blood-borne infections (STBBIs) among men who purchase sex from female sex workers.

Host genetic variation at a locus near CHD1L impacts HIV sequence diversity in a South African population.

It has been previously shown that genetic variants near on chromosome 1 are associated with reduced HIV VL in African populations. However, the impact of these variants on viral diversity and how they restrict viral replication are unknown. We report on a regional association analysis in a South African population and show evidence of selective pressure by variants near on HIV RT and gag.

Blood monocyte and dendritic cell profiles among people living with HIV with Mycobacterium tuberculosis co-infection.

Background: Understanding the complex interactions of the immune response mediated by Mycobacterium tuberculosis and HIV co-infection is fundamental to disease biomarker discovery, vaccine, and drug development. Using flow cytometry, we characterized the frequencies and phenotypic differences in monocytes and dendritic cell populations using peripheral blood mononuclear cells from individuals with recurrent, active pulmonary tuberculosis with and without coexisting HIV infection (CAPRISA 011, Clinicaltrials.gov, NCT02114684, 29/01/2014) and compared them to samples from HIV positive individuals and healthy controls.

Immune resilience despite inflammatory stress promotes longevity and favorable health outcomes including resistance to infection.

Some people remain healthier throughout life than others but the underlying reasons are poorly understood. Here we hypothesize this advantage is attributable in part to optimal immune resilience (IR), defined as the capacity to preserve and/or rapidly restore immune functions that promote disease resistance (immunocompetence) and control inflammation in infectious diseases as well as other causes of inflammatory stress. We gauge IR levels with two distinct peripheral blood metrics that quantify the balance between (i) CD8 and CD4 T-cell levels and (ii) gene expression signatures tracking longevity-associated immunocompetence and mortality-associated inflammation.

Geographical Associations of HIV Prevalence in Female Sex Workers From Nairobi, Kenya (2014-2017).

Background: Kenya's HIV epidemic is heterogeneously distributed. Although HIV incidence in Kenya has shown signs of recent decline, focused interventions are still needed for female sex workers (FSWs). Geospatially informed approaches have been advocated for targeted HIV prevention.

Nonoptimal bacteria species induce neutrophil-driven inflammation and barrier disruption in the female genital tract.

Neutrophil recruitment and activation within the female genital tract are often associated with tissue inflammation, loss of vaginal epithelial barrier integrity, and increased risk for sexually transmitted infections, such as HIV-1. However, the direct role of neutrophils on vaginal epithelial barrier function during genital inflammation in vivo remains unclear. Using complementary proteome and immunological analyses, we show high neutrophil influx into the lower female genital tract in response to physiological surges in progesterone, stimulating distinct stromal, immunological, and metabolic signaling pathways.

HIV acquisition prior to entry into formal sex work: inference from next-generation viral sequencing.

Objective: To infer the timing of HIV acquisition in relation to self-reported events in the sexual life course of adolescent girls and young women (AGYW) who self-identify as female sex workers (FSW) in Mombasa, Kenya.

Design: Next-generation viral sequencing of samples of AGYW living with HIV in the Transitions study, a cross-sectional bio-behavioural survey of AGYW aged 14-24 years in Mombasa, Kenya.

Method: Dried blood spot specimens were collected from study participants ( n  = 37, all FSW).

subgroup dominant microbiomes are associated with divergent cervicovaginal immune responses in a longitudinal cohort of Kenyan women.

Most cervicovaginal microbiome-immunology studies to date have relied on 16S rDNA microbial profiling which does not resolve the molecular subgroups of , believed to be central to the pathogenesis of bacterial vaginosis (BV) and subsequent risk of HIV acquisition. Here we used the 60 universal target which in addition to other microbial taxa, resolves four subgroups, for cervicovaginal microbial profiling in a longitudinal cohort of Kenyan women to examine associations with cellular and soluble markers of inflammation and HIV susceptibility. Participants (N = 41) were sampled, contributing 362 samples for microbiome analysis.

Non-Lactobacillus-Dominant and Polymicrobial Vaginal Microbiomes Are More Common in Younger South African Women and Predictive of Increased Risk of Human Immunodeficiency Virus Acquisition.

Background: Adolescent girls and young women aged 15‒24 years in sub-Saharan Africa are at disproportionate risk of human immunodeficiency virus (HIV) infection. Given the known association between vaginal microbial dysbiosis and HIV susceptibility, we performed an age-stratified analysis of the vaginal microbiome in South African women and compared this to their risk of HIV acquisition.

Methods: Vaginal microbiome data were generated by mass spectrometry-based proteomic analysis of cervicovaginal lavages collected from participants (n = 688) in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 trial.

Baseline host determinants of robust human HIV-1 vaccine-induced immune responses: A meta-analysis of 26 vaccine regimens.

Background: The identification of baseline host determinants that associate with robust HIV-1 vaccine-induced immune responses could aid HIV-1 vaccine development. We aimed to assess both the collective and relative performance of baseline characteristics in classifying individual participants in nine different Phase 1-2 HIV-1 vaccine clinical trials (26 vaccine regimens, conducted in Africa and in the Americas) as High HIV-1 vaccine responders.

Methods: This was a meta-analysis of individual participant data, with studies chosen based on participant-level (vs.

The functional diversity of tissue-resident natural killer cells against infection.

For decades, studies of natural killer (NK) cells have focused on those found in peripheral blood (PBNK cells) as the prototype for NK cell biology. Only recently have researchers begun to explore the diversity of tissue-resident NK (tr-NK) cells. While tr-NK cells were initially identified from mice parabiosis and intravascular staining experiments, they can also be identified by tissue retention markers such as CD69, CD103 and others.

Expansion of cytotoxic tissue-resident CD8 T cells and CCR6CD161 CD4 T cells in the nasal mucosa following mRNA COVID-19 vaccination.

Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the human upper respiratory tract, is less well known. Here, we enumerate and phenotype T cells in nasal mucosa and blood using flow cytometry before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n = 21). Tissue-resident memory (Trm) CD8 T cells expressing CD69CD103 increase in number ~12 days following the first and second doses, by 0.

Viral suppression among pregnant adolescents and women living with HIV in rural KwaZulu-Natal, South Africa: a cross sectional study to assess progress towards UNAIDS indicators and Implications for HIV Epidemic Control.

Background: South Africa has made significant progress in scaling up antiretroviral therapy (ART) to achieve the aspirational goal of HIV epidemic control. The aim of this study was to determine the prevalence of HIV, assess progress towards each of the Joint United Nations Programme on HIV/AIDS (UNAIDS) indicators and determine factors associated with achieving viral suppression among pregnant adolescents and women living with HIV in rural KwaZulu-Natal, South Africa.

Methods: Pregnant adolescents and women, 12 years and older seeking antenatal care at six primary health care clinics were enrolled in a cross-sectional study.