23 research outputs found
Immunological correlates of protection afforded by PHV02 live, attenuated recombinant vesicular stomatitis virus vector vaccine against Nipah virus disease
IntroductionImmune correlates of protection afforded by PHV02, a recombinant vesicular stomatitis (rVSV) vector vaccine against Nipah virus (NiV) disease, were investigated in the African green monkey (AGM) model. Neutralizing antibody to NiV has been proposed as the principal mediator of protection against future NiV infection.MethodsTwo approaches were used to determine the correlation between neutralizing antibody levels and outcomes following a severe (1,000 median lethal doses) intranasal/intratracheal (IN/IT) challenge with NiV (Bangladesh): (1) reduction in vaccine dose given 28 days before challenge and (2) challenge during the early phase of the antibody response to the vaccine.ResultsReduction in vaccine dose to very low levels led to primary vaccine failure rather than a sub-protective level of antibody. All AGMs vaccinated with the nominal clinical dose (2 × 107 pfu) at 21, 14, or 7 days before challenge survived. AGMs vaccinated at 21 days before challenge had neutralizing antibodies (geometric mean titer, 71.3). AGMs vaccinated at 7 or 14 days before challenge had either undetectable or low neutralizing antibody titers pre-challenge but had a rapid rise in titers after challenge that abrogated the NiV infection. A simple logistic regression model of the combined studies was used, in which the sole explanatory variable was pre-challenge neutralizing antibody titers. For a pre-challenge titer of 1:5, the predicted survival probability is 100%. The majority of animals with pre-challenge neutralizing titer of ≥1:20 were protected against pulmonary infiltrates on thoracic radiograms, and a majority of those with titers ≥1:40 were protected against clinical signs of illness and against a ≥fourfold antibody increase following challenge (indicating sterile immunity). Controls receiving rVSV-Ebola vaccine rapidly succumbed to NiV challenge, eliminating the innate immunity stimulated by the rVSV vector as a contributor to survival in monkeys challenged as early as 7 days after vaccination.Discussion and conclusionIt was concluded that PHV02 vaccine elicited a rapid onset of protection and that any detectable level of neutralizing antibody was a functional immune correlate of survival
Control of the HIV-1 Load Varies by Viral Subtype in a Large Cohort of African Adults With Incident HIV-1 Infection.
Few human immunodeficiency virus (HIV)-infected persons can maintain low viral levels without therapeutic intervention. We evaluate predictors of spontaneous control of the viral load (hereafter, "viral control") in a prospective cohort of African adults shortly after HIV infection. Viral control was defined as ≥2 consecutively measured viral loads (VLs) of ≤10 000 copies/mL after the estimated date of infection, followed by at least 4 subsequent measurements for which the VL in at least 75% was ≤10 000 copies/mL in the absence of ART. Multivariable logistic regression characterized predictors of viral control. Of 590 eligible volunteers, 107 (18.1%) experienced viral control, of whom 25 (4.2%) maintained a VL of 51-2000 copies/mL, and 5 (0.8%) sustained a VL of ≤50 copies/mL. The median ART-free follow-up time was 3.3 years (range, 0.3-9.7 years). Factors independently associated with control were HIV-1 subtype A (reference, subtype C; adjusted odds ratio [aOR], 2.1 [95% confidence interval {CI}, 1.3-3.5]), female sex (reference, male sex; aOR, 1.8 [95% CI, 1.1-2.8]), and having HLA class I variant allele B*57 (reference, not having this allele; aOR, 1.9 [95% CI, 1.0-3.6]) in a multivariable model that also controlled for age at the time of infection and baseline CD4+ T-cell count. We observed strong associations between infecting HIV-1 subtype, HLA type, and sex on viral control in this cohort. HIV-1 subtype is important to consider when testing and designing new therapeutic and prevention technologies, including vaccines
S1 Dataset -
IntroductionHepatitis B (HBV) prevalence remains high in Sub Saharan Africa and among some key populations such as those with continued exposure through sexual contact. We assessed the HBV status among potential participants who were screened for simulated HIV vaccine efficacy trials in Kenya and Uganda.MethodsWe conducted a cross sectional analysis of data collected from individuals who were screened in Kenya (Nairobi) and Uganda (Entebbe and Kampala). The studies followed hypothetical procedures of an HIV vaccine efficacy trial and aimed to enroll HIV negative key and vulnerable populations at elevated risk of HIV acquisition. HBV status was the main outcome categorized using Hepatitis B surface antigen (HBsAg) and total Hepatitis B core antibody (HBcAb). Baseline characteristics potentially associated with never being infected were analyzed using logistic regression.ResultsWe screened 1,366 participants with mean age (SD) 28.7 (7.3) years. Overall, 46.6% were from Entebbe, 50.7% had secondary or higher level of education, 76.4% had informal high-risk jobs and 56.3% were male. Kampala had only female participants contributing 60.6% of females screened. Of the screened participants, 94.7% and 3.4% were negative and positive for HBsAg respectively. The prevalence on HBV infection was 3.9% among males and 2.8% among females while prevalence by site was: Entebbe (4.9%); Kampala (4.1%) and Nairobi (0.3%). The highest HBV prevalence was found among participants aged 25-29-years (5.2%), those with primary level education (4.5%), and those in informal low risk jobs (6.5%). Considering 1265 participants with complete data on HBsAg and HBcAb-Total, HBV status was never infected (67.9%), past infection (28.5%), chronic infection (3.2%) and acute infection (0.5%). Of 859 who were never infected, 685 (79.7%) were tested for anti-HBs titers of whom 60 (8.8%) had titers >10IU/L (immune due to vaccination). The odds of never being HBV infected were lower among older individuals 25–29 years (AOR 0.51; 95%CI 0.36–0.71) and ≥30 years (AOR 0.35; 95% CI 0.25–0.49). The odds were higher among participants with informal high-risk jobs from Kampala (AOR 2.21; 95% CI 1.41–3.47) and Nairobi (AOR 2.61; 95% CI 1.72–4.00) compared to those from Entebbe.ConclusionHBV prevalence and immunity due to vaccination were low among HIV negative individuals who are eligible for HIV vaccine trials and prevalence varies by age, education level and main occupation. Younger individuals and those recruited from existing cohorts/ clinics have a higher likelihood of having no prior HBV infection. HIV prevention intervention trials are a platform to identify individuals that need HBV vaccination.</div
Hepatitis B status of participants screened for the SiVET studies in Kenya and Uganda by baseline characteristics.
Hepatitis B status of participants screened for the SiVET studies in Kenya and Uganda by baseline characteristics.</p
Socio-demographic characteristics by site of participants screened for SiVET studies in Kenya and Uganda (2014–2017).
Socio-demographic characteristics by site of participants screened for SiVET studies in Kenya and Uganda (2014–2017).</p
Assays used by participating research centers to screen for Hepatitis B.
Assays used by participating research centers to screen for Hepatitis B.</p
Characteristics associated with having no prior Hepatitis B infection among participants screened for SiVET studies in Kenya and Uganda (n = 1265).
Characteristics associated with having no prior Hepatitis B infection among participants screened for SiVET studies in Kenya and Uganda (n = 1265).</p
Characteristics associated with Hepatitis B surface antigen positivity among participants screened for SiVET studies in Kenya and Uganda (n = 1340).
Characteristics associated with Hepatitis B surface antigen positivity among participants screened for SiVET studies in Kenya and Uganda (n = 1340).</p
Dataset: Tathmini GBV study: Evaluation of comprehensive gender-based violence programming delivered through the HIV program platform in Tanzania
The Tathmini GBV study was a cluster randomized trial to assess the impact of a comprehensive health facility- and community-based program delivered through the HIV/AIDS program platform on reduction in gender-based violence and improved care for survivors. The study demonstrated the feasibility and impact of integrating gender-based violence and HIV programming to combat both of these major public health problems. Further opportunities to scale out GBV prevention and response strategies within HIV/AIDS service delivery platforms should be pursued
Cluster randomized trial of comprehensive gender-based violence programming delivered through the HIV/AIDS program platform in Mbeya Region, Tanzania: Tathmini GBV study.
The Tathmini GBV study was a cluster randomized trial to assess the impact of a comprehensive health facility- and community-based program delivered through the HIV/AIDS program platform on reduction in gender-based violence and improved care for survivors. Twelve health facilities and surrounding communities in the Mbeya Region of Tanzania were randomly assigned to intervention or control arms. Population-level effects were measured through two cross-sectional household surveys of women ages 15-49, at baseline (n = 1,299) and at 28 months following program scale-out (n = 1,250). Delivery of gender-based violence services was assessed through routine recording in health facility registers. Generalized linear mixed effects models and analysis of variance were used to test intervention effects on population and facility outcomes, respectively. At baseline, 52 percent of women reported experience of recent intimate partner violence. The odds of reporting experience of this violence decreased by 29 percent from baseline to follow-up in the absence of the intervention (time effect OR = 0.71, 95% CI: 0.57-0.89). While the intervention contributed an additional 15 percent reduction, the effect was not statistically significant. The program, however, was found to contribute to positive, community-wide changes including less tolerance for certain forms of violence, more gender equitable norms, better knowledge about gender-based violence, and increased community actions to address violence. The program also led to increased utilization of gender-based violence services at health facilities. Nearly three times as many client visits for gender-based violence were recorded at intervention (N = 1,427) compared to control (N = 489) facilities over a 16-month period. These visits were more likely to include provision of an HIV test (55.3% vs. 19.6%, p = .002). The study demonstrated the feasibility and impact of integrating gender-based violence and HIV programming to combat both of these major public health problems. Further opportunities to scale out GBV prevention and response strategies within HIV/AIDS service delivery platforms should be pursued. Trial Registration: Pan African Clinical Trials Registry No. PACTR201802003124149