Delineating the functional activity of antibodies with cross-reactivity to SARS-CoV-2, SARS-CoV-1 and related sarbecoviruses.

The recurring spillover of pathogenic coronaviruses and demonstrated capacity of sarbecoviruses, such SARS-CoV-2, to rapidly evolve in humans underscores the need to better understand immune responses to this virus family. For this purpose, we characterized the functional breadth and potency of antibodies targeting the receptor binding domain (RBD) of the spike glycoprotein that exhibited cross-reactivity against SARS-CoV-2 variants, SARS-CoV-1 and sarbecoviruses from diverse clades and animal origins with spillover potential. One neutralizing antibody, C68.

Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection.

The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines.

Reconstruction of a polyclonal ADCC antibody repertoire from an HIV-1 non-transmitting mother.

Human natural history and vaccine studies support a protective role of antibody dependent cellular cytotoxicity (ADCC) activity against many infectious diseases. One setting where this has consistently been observed is in HIV-1 vertical transmission, where passively acquired ADCC activity in HIV-exposed infants has correlated with reduced acquisition risk and reduced pathogenesis in HIV+ infants. However, the characteristics of HIV-specific antibodies comprising a maternal plasma ADCC response are not well understood.

Identification of broad, potent antibodies to functionally constrained regions of SARS-CoV-2 spike following a breakthrough infection.

The antiviral benefit of antibodies can be compromised by viral escape especially for rapidly evolving viruses. Therefore, durable, effective antibodies must be both broad and potent to counter newly emerging, diverse strains. Discovery of such antibodies is critically important for SARS-CoV-2 as the global emergence of new variants of concern (VOC) has compromised the efficacy of therapeutic antibodies and vaccines.

Functional development of a V3/glycan-specific broadly neutralizing antibody isolated from a case of HIV superinfection.

Stimulating broadly neutralizing antibodies (bnAbs) directly from germline remains a barrier for HIV vaccines. HIV superinfection elicits bnAbs more frequently than single infection, providing clues of how to elicit such responses. We used longitudinal antibody sequencing and structural studies to characterize bnAb development from a superinfection case.

A diverse collection of B cells responded to HIV infection in infant BG505.

Increasing evidence suggests infants develop unique neutralizing antibody (nAb) responses to HIV compared to adults. Here, we dissected the nAb response of an infant whose virus is in clinical trials as a vaccine immunogen, with a goal of characterizing the broad responses in the infant to this antigen. We isolated 73 nAbs from infant BG505 and identified a large number of clonal families.

Correlates of HIV detection among breastfeeding postpartum Kenyan women eligible under Option B.

Background: The Option B+ strategy streamlines delivery of HIV antiretroviral therapy (ART) to pregnant women, but concerns remain about ART treatment adherence and long term outcomes.

Methods: We conducted a retrospective analysis of a cohort of HIV-positive, postpartum breastfeeding women receiving ART via Option B+ in Nairobi, Kenya. The primary outcome was virologic failure in plasma (HIV RNA >1000 copies/mL), and detection in breast milk (>150 copies/mL) and endocervical secretions (>100 copies/mL) at 2 postpartum timepoints.

Gender-Based Violence, Physiological Stress, and Inflammation: A Cross-Sectional Study.

Background: Female sex workers (FSWs) are at high risk for gender-based violence (GBV) and HIV infection. This study aimed to identify associations between GBV exposure in the past 12 months and biomarkers of physiologic stress and inflammation that may play a role in increased HIV risk among Kenyan FSWs.

Materials And Methods: Participating women responded to a detailed questionnaire on GBV and mental health.

Genital Shedding of Resistant Human Immunodeficiency Virus-1 Among Women Diagnosed With Treatment Failure by Clinical and Immunologic Monitoring.

Background.  The accumulation of human immunodeficiency virus (HIV) resistance mutations can compromise treatment outcomes and promote transmission of drug-resistant virus. We conducted a study to determine the duration and evolution of genotypic drug resistance in the female genital tract among HIV-1-infected women failing first-line therapy.

Maternal Neutralization-Resistant Virus Variants Do Not Predict Infant HIV Infection Risk.

Unlabelled: Mother-to-child transmission (MTCT) of HIV provides a setting for studying immune correlates of protection. Neutralizing antibodies (NAbs) are suggested to contribute to a viral bottleneck during MTCT, but their role in blocking transmission is unclear, as studies comparing the NAb sensitivities of maternal viruses have yielded disparate results. We sought to determine whether transmitting mothers differ from nontransmitting mothers in the ability to neutralize individual autologous virus variants present at transmission.

Early development of broadly neutralizing antibodies in HIV-1-infected infants.

Eliciting protective neutralizing antibodies (NAbs) against HIV-1 is daunting because of the extensive genetic and antigenic diversity of HIV-1. Moreover, broad and potent responses are uncommon even during persistent infection, with only a subset of adults developing broadly neutralizing antibodies (bNAbs) that recognize viral variants from different HIV-1 clades. It is not known whether bNAbs can also arise in HIV-1-infected infants, who typically progress to disease faster than adults, presumably in part due to an immature immune system.

A prospective cohort study of the effect of depot medroxyprogesterone acetate on detection of plasma and cervical HIV-1 in women initiating and continuing antiretroviral therapy.

Depot medroxyprogesterone acetate (DMPA) use among HIV-1-infected women may increase transmission by increasing plasma and genital HIV-1 RNA shedding. We investigated associations between DMPA use and HIV-1 RNA in plasma and cervical secretions. One hundred two women initiated antiretroviral therapy, contributing 925 follow-up visits over a median of 34 months.

A prospective cohort study comparing the effect of single-dose 2 g metronidazole on Trichomonas vaginalis infection in HIV-seropositive versus HIV-seronegative women.

Background: This analysis compared the frequency of persistent Trichomonas vaginalis (TV) among HIV-seropositive and HIV-seronegative women.

Methods: Data were obtained from women enrolled in an open cohort study of sex workers in Kenya. Participants were examined monthly, and those diagnosed as having TV by saline microscopy were treated with single-dose 2 g oral metronidazole.

Antiretroviral treatment interruptions predict female genital shedding of genotypically resistant HIV-1 RNA.

Objectives: Resistant viruses may emerge in the female genital tract during antiretroviral therapy (ART). Our objective was to identify predictors of drug-resistant HIV-1 RNA in genital secretions after initiation of nonnucleoside reverse transcriptase inhibitor-based therapy.

Design: We conducted a prospective cohort study with periodic evaluation of plasma and genital swab samples for HIV-1 RNA levels and antiretroviral resistance mutations.

The neutralization sensitivity of viruses representing human immunodeficiency virus type 1 variants of diverse subtypes from early in infection is dependent on producer cell, as well as characteristics of the specific antibody and envelope variant.

Neutralization properties of human immunodeficiency virus (HIV-1) are often defined using pseudoviruses grown in transformed cells, which are not biologically relevant HIV-1 producer cells. Little information exists on how these viruses compare to viruses produced in primary lymphocytes, particularly for globally relevant HIV-1 strains. Therefore, replication-competent chimeras encoding envelope variants from the dominant HIV-1 subtypes (A, C, and D) obtained early after infection were generated and the neutralization properties explored.

Effect of acquisition and treatment of cervical infections on HIV-1 shedding in women on antiretroviral therapy.

Background: Cervicitis increases the quantity of HIV-1 RNA in cervical secretions when women are not taking antiretroviral therapy (ART), and successful treatment of cervicitis reduces HIV-1 shedding in this setting.

Objective: To determine the effect of acquisition and treatment of cervical infections on genital HIV-1 shedding in women receiving ART.

Design: Prospective cohort study.

Improvement of vaginal health for Kenyan women at risk for acquisition of human immunodeficiency virus type 1: results of a randomized trial.

Background: Vaginal infections are common and have been associated with increased risk for acquisition of human immunodeficiency virus type 1 (HIV-1).

Methods: We conducted a randomized trial of directly observed oral treatment administered monthly to reduce vaginal infections among Kenyan women at risk for HIV-1 acquisition. A trial intervention of 2 g of metronidazole plus 150 mg of fluconazole was compared with metronidazole placebo plus fluconazole placebo.

Chronic HIV-1 infection frequently fails to protect against superinfection.

Reports of HIV-1 superinfection (re-infection) have demonstrated that the immune response generated against one strain of HIV-1 does not always protect against other strains. However, studies to determine the incidence of HIV-1 superinfection have yielded conflicting results. Furthermore, few studies have attempted to identify superinfection cases occurring more than a year after initial infection, a time when HIV-1-specific immune responses would be most likely to have developed.

HIV-1 subtype D infection is associated with faster disease progression than subtype A in spite of similar plasma HIV-1 loads.

We investigated the effect of human immunodeficiency virus type 1 (HIV-1) subtype on disease progression among 145 Kenyan women followed from the time of HIV-1 acquisition. Compared with those infected with subtype A, women infected with subtype D had higher mortality (hazard ratio, 2.3 [95% confidence interval, 1.

Associations between intravaginal practices and bacterial vaginosis in Kenyan female sex workers without symptoms of vaginal infections.

Background: Bacterial vaginosis (BV) is highly prevalent among African women and has been associated with adverse pregnancy outcomes, sexually transmitted diseases, and HIV-1.

Goal: The goal of this study was to analyze the relationship among intravaginal practices, bathing, and BV.

Study Design: The authors conducted a cross-sectional study of HIV-1-seronegative Kenyan female sex workers without symptoms of vaginal infections.

Contribution of HIV-1 infection to acquisition of sexually transmitted disease: a 10-year prospective study.

Background: Sexually transmitted diseases (STDs) enhance human immunodeficiency virus (HIV)-1 susceptibility, but few studies have examined the reciprocal effect of HIV-1 on STD acquisition.

Methods: Data from a prospective cohort study conducted among female sex workers in Mombasa, Kenya between 1993 and 2003 were used to determine the effect of HIV-1 infection on STD susceptibility. The cohort included 1215 HIV-1-seronegative women who underwent monthly HIV-1 and STD screening, of whom 238 experienced seroconversion to HIV-1 during follow-up.