Contraception use and pregnancy in women receiving a 2-dose Ebola vaccine in Rwanda: A retrospective analysis of UMURINZI vaccination campaign data.

Background: Rwandan individuals bordering the Democratic Republic of the Congo (DRC) are at-risk of Ebola virus disease. A 2019 to 2021 vaccination campaign called UMURINZI offered a Janssen Vaccines & Prevention B.V.

Dynamics of the blood plasma proteome during hyperacute HIV-1 infection.

The complex dynamics of protein expression in plasma during hyperacute HIV-1 infection and its relation to acute retroviral syndrome, viral control, and disease progression are largely unknown. Here, we quantify 1293 blood plasma proteins from 157 longitudinally linked plasma samples collected before, during, and after hyperacute HIV-1 infection of 54 participants from four sub-Saharan African countries. Six distinct longitudinal expression profiles are identified, of which four demonstrate a consistent decrease in protein levels following HIV-1 infection.

Phenotypic Characterization of Subtype A and Recombinant AC Transmitted/Founder Viruses from a Rwandan HIV-1 Heterosexual Transmission Cohort.

HIV-1 subtypes have distinct geographical distributions, with subtypes A, C, and D and inter-subtype recombinants circulating in sub-Saharan Africa. Historically, individuals living with subtype A viruses exhibit slower CD4 decline and progression to AIDS diagnosis. Despite this, there are few authentic infectious molecular clones (IMCs) of subtype A or AC recombinant transmitted founder (TF) viruses with which to investigate viral impacts on pathogenesis.

Uptake and perceptions of voluntary medical male circumcision among HIV-negative men in serodiscordant relationships in Zambia (2012-2015).

Voluntary medical male circumcision (VMMC) is a recommended HIV prevention strategy that few studies have promoted to HIV-negative men in serodiscordant relationships. We conducted a cross-sectional study on uptake and perceptions of VMMC among serodiscordant couples between 2012 and 2015. Heterosexual couples attending couples voluntary counselling and testing for HIV who had discordant results (M-, F+) were referred for VMMC.

The role of Zambia's expansive Inter-agency Coordinating Committee (ICC) in supporting evidence-based vaccine and health sector programming.

New vaccines, technologies, and regulations, alongside increased demand for vaccines, all require prioritization and coordination from key players within the vaccine sector. Inter-agency Coordinating Committees (ICC) support decision-making and coordination at the national-level and act as key drivers for sustainable improvements in vaccination programming. We utilized a previous qualitative case study, which investigated critical success factors for high routine immunization coverage in Zambia from 2000-2018, specifically to study the Zambian ICC.

Success in vaccination programming through community health workers: a qualitative analysis of interviews and focus group discussions from Nepal, Senegal and Zambia.

Objectives: Community health workers are essential to front-line health outreach throughout low-income and middle-income countries, including programming for early childhood immunisation. Understanding how community health workers are engaged for successful early childhood vaccination among countries who showed success in immunisation coverage would support evidence-based policy guidance across contexts.

Design: We employed a multiple case study design using qualitative research methods.

Low pre-existing endemic human coronavirus (HCoV-NL63)-specific T cell frequencies are associated with impaired SARS-CoV-2-specific T cell responses in people living with HIV.

Background: Understanding how HIV affects SARS-CoV-2 immunity is crucial for managing COVID-19 in sub-Saharan populations due to frequent coinfections. Our previous research showed that unsuppressed HIV is associated with weaker immune responses to SARS-CoV-2, but the underlying mechanisms are unclear. We investigated how pre-existing T cell immunity against an endemic human coronavirus HCoV-NL63 impacts SARS-CoV-2 T cell responses in people living with HIV (PLWH) compared to uninfected individuals, and how HIV-related T cell dysfunction influences responses to SARS-CoV-2 variants.

Female Genital Schistosomiasis Lesion Resolution Post-Treatment with Praziquantel in Zambian Adults.

We evaluated changes in female genital schistosomiasis (FGS) 6 to 12 months after praziquantel treatment among 43 adult Zambian women. Most women (60%) experienced decreased FGS severity and 23% experienced complete lesion resolution. This is the first study to demonstrate a meaningful effect of praziquantel treatment of FGS in adult women.

High throughput analysis of B cell dynamics and neutralizing antibody development during immunization with a novel clade C HIV-1 envelope.

A protective HIV-1 vaccine has been hampered by a limited understanding of how B cells acquire neutralizing activity. Our previous vaccines expressing two different HIV-1 envelopes elicited robust antigen specific serum IgG titers in 20 rhesus macaques; yet serum from only two animals neutralized the autologous virus. Here, we used high throughput immunoglobulin receptor and single cell RNA sequencing to characterize the overall expansion, recall, and maturation of antigen specific B cells longitudinally over 90 weeks.

Africa-specific human genetic variation near CHD1L associates with HIV-1 load.

HIV-1 remains a global health crisis, highlighting the need to identify new targets for therapies. Here, given the disproportionate HIV-1 burden and marked human genome diversity in Africa, we assessed the genetic determinants of control of set-point viral load in 3,879 people of African ancestries living with HIV-1 participating in the international collaboration for the genomics of HIV. We identify a previously undescribed association signal on chromosome 1 where the peak variant associates with an approximately 0.

Monitoring of Adverse Events in Recipients of the 2-Dose Ebola Vaccine Regimen of Ad26.ZEBOV Followed by MVA-BN-Filo in the UMURINZI Ebola Vaccination Campaign.

Background: From 2019 to 2021, Rwandan residents of the border with the Democratic Republic of the Congo were offered the Ad26.ZEBOV (adenovirus type 26 vector vaccine encoding Ebola virus glycoprotein) and MVA-BN-Filo (modified vaccinia virus Ankara vector vaccine, encoding glycoproteins from Ebola, Sudan, Marburg, and nucleoprotein from Tai Forest viruses) Ebola vaccine regimen.

Methods: Nonpregnant persons aged ≥2 years were eligible.

Safety, reactogenicity, and immunogenicity of a 2-dose Ebola vaccine regimen of Ad26.ZEBOV followed by MVA-BN-Filo in healthy adult pregnant women: study protocol for a phase 3 open-label randomized controlled trial.

Background: Risks to mother and fetus following Ebola virus infection are very high. Evaluation of safety and immunogenicity of non-replicating Ebola vaccine candidates is a priority for use in pregnant women. This is the protocol for a randomized, open-label, single-center phase 3 clinical trial of the safety, reactogenicity, and immunogenicity of the 2-dose Ebola vaccine regimen in healthy adult pregnant women.

Critical success factors for routine immunization performance: A case study of Zambia 2000 to 2018.

Introduction: The essential components of a vaccine delivery system are well-documented, but robust evidence on how and why the related processes and implementation strategies prove effective at driving coverage is not well-established. To address this gap, we identified critical success factors associated with advancing key policies and programs that may have led to the substantial changes in routine childhood immunization coverage in Zambia between 2000 and 2018.

Methods: We identified Zambia as an exemplar in the delivery of childhood vaccines through analysis of DTP1 and DTP3 coverage data.

A neutralizing antibody target in early HIV-1 infection was recapitulated in rhesus macaques immunized with the transmitted/founder envelope sequence.

Transmitted/founder (T/F) HIV-1 envelope proteins (Envs) from infected individuals that developed neutralization breadth are likely to possess inherent features desirable for vaccine immunogen design. To explore this premise, we conducted an immunization study in rhesus macaques (RM) using T/F Env sequences from two human subjects, one of whom developed potent and broad neutralizing antibodies (Z1800M) while the other developed little to no neutralizing antibody responses (R66M) during HIV-1 infection. Using a DNA/MVA/protein immunization protocol, 10 RM were immunized with each T/F Env.

Implementation and evaluation of a large-scale postpartum family planning program in Rwanda: study protocol for a clinic-randomized controlled trial.

Background: Though the Rwandan Ministry of Health (MOH) prioritizes the scale-up of postpartum family planning (PPFP) programs, uptake and sustainability of PPFP services in Rwanda are low. Furthermore, highly effective long-acting reversible contraceptive method use (LARC), key in effective PPFP programs, is specifically low in Rwanda. We previously pilot tested a supply-demand intervention which significantly increased the use of postpartum LARC (PPLARC) in Rwandan government clinics.

Measles immunity gap among reproductive-age women participating in a simulated HIV vaccine efficacy trial in Zambia.

Measles is a vaccine-preventable viral disease whose vaccination coverage remains low in Zambia, where the target group for vaccination is children aged 9 to 18 months. In addition to inadequate measles vaccination coverage among children, few studies address potential resultant immunity gaps among adults. We analyzed data from a simulated HIV vaccine efficacy trial (SiVET) conducted from 2015-2017 among adult Zambian women of childbearing age to determine measles antibody seroprevalence before and after vaccination with the measles, mumps and rubella (MMR) vaccine.

Hepatic safety and tolerability of cipargamin (KAE609), in adult patients with Plasmodium falciparum malaria: a randomized, phase II, controlled, dose-escalation trial in sub-Saharan Africa.

Background: The novel anti-malarial cipargamin (KAE609) has potent, rapid activity against Plasmodium falciparum. Transient asymptomatic liver function test elevations were previously observed in cipargamin-treated subjects in two trials: one in malaria patients in Asia and one in volunteers with experimentally induced malaria. In this study, the hepatic safety of cipargamin given as single doses of 10 to 150 mg and 10 to 50 mg once daily for 3 days was assessed.

Efficacy of Cipargamin (KAE609) in a Randomized, Phase II Dose-Escalation Study in Adults in Sub-Saharan Africa With Uncomplicated Plasmodium falciparum Malaria.

Background: Cipargamin (KAE609) is a potent antimalarial in a phase II trial. Here we report efficacy, pharmacokinetics, and resistance marker analysis across a range of cipargamin doses. These were secondary endpoints from a study primarily conducted to assess the hepatic safety of cipargamin (hepatic safety data are reported elsewhere).

Evolution of Condom Use Among a 5-Year Cohort of Female Sex Workers in Zambia.

Observing sexual behaviour change over time could help develop behavioural HIV prevention interventions for female sex workers in Zambia, where these interventions are lacking. We investigated the evolution of consistent condom use among female sex workers and their clients and steady partners. Participants were recruited into an HIV incidence cohort from 2012 to 2017.

Leapfrogging with technology: introduction of a monitoring platform to support a large-scale Ebola vaccination program in Rwanda.

Continued outbreaks of Ebola virus disease, including recent outbreaks in the Democratic Republic of the Congo (DRC), highlight the need for effective vaccine programs to combat future outbreaks. Given the population flow between DRC and Rwanda, the Rwanda Ministry of Health initiated a preventive vaccination campaign supported by a vaccination monitoring platform (VMP). The campaign aimed to vaccinate approximately 200,000 people from Rwanda's Rubavu and Rusizi districts with the two-dose vaccine regimen Ad26.

Utilizing Computational Machine Learning Tools to Understand Immunogenic Breadth in the Context of a CD8 T-Cell Mediated HIV Response.

Predictive models are becoming more and more commonplace as tools for candidate antigen discovery to meet the challenges of enabling epitope mapping of cohorts with diverse HLA properties. Here we build on the concept of using two key parameters, diversity metric of the HLA profile of individuals within a population and consideration of sequence diversity in the context of an individual's CD8 T-cell immune repertoire to assess the HIV proteome for defined regions of immunogenicity. Using this approach, analysis of HLA adaptation and functional immunogenicity data enabled the identification of regions within the proteome that offer significant conservation, HLA recognition within a population, low prevalence of HLA adaptation and demonstrated immunogenicity.