Two dimensional nanosheets as immunoregulator improve HIV vaccine efficacy

2D NSs target lymph nodes and activate macrophages to enhance vaccine-induced immune responses via regulating six critical genes (Ccr2, Serpinb9, Klrk1, Klrd1, Klrc1, Msr1).

Different adjuvanted pediatric HIV envelope vaccines induced distinct plasma antibody responses despite similar B cell receptor repertoires in infant rhesus macaques

Different HIV vaccine regimens elicit distinct plasma antibody responses in both human and nonhuman primate models. Previous studies in human and non-human primate infants showed that adjuvants influenced the quality of plasma antibody responses induced by pediatric HIV envelope vaccine regimens. We recently reported that use of the 3M052-SE adjuvant and longer intervals between vaccinations are associated with higher magnitude of antibody responses in infant rhesus macaques. However, the impact of different adjuvants in HIV vaccine regimens on the developing infant B cell receptor (BCR) repertoire has not been studied. This study evaluated whether pediatric HIV envelope vaccine regimens with different adjuvants induced distinct antigen-specific memory B cell repertoires and whether specific immunoglobulin (Ig) immunogenetic characteristics are associated with higher magnitude of plasma antibody responses in vaccinated infant rhesus macaques. We utilized archived preclinical pediatric HIV vaccine studies PBMCs and tissue samples from 19 infant rhesus macaques immunized either with (i) HIV Env protein with a squalene adjuvant, (ii) MVA-HIV and Env protein co-administered using a 3-week interval, (iii) MVA-HIV prime/ protein boost with an extended 6-week interval between immunizations, or (iv) with HIV Env administered with 3M-052-SE adjuvant. Frequencies of vaccine-elicited HIV Env-specific memory B cells from PBMCs and tissues were similar across vaccination groups (frequency range of 0.06–1.72%). There was no association between vaccine-elicited antigen-specific memory B cell frequencies and plasma antibody titer or avidity. Moreover, the epitope specificity and Ig immunogenetic features of vaccine-elicited monoclonal antibodies did not differ between the different vaccine regimens. These data suggest that pediatric HIV envelope vaccine candidates with different adjuvants that previously induced higher magnitude and quality of plasma antibody responses in infant rhesus macaques were not driven by distinct antigen-specific memory BCR repertoires.

Establishing communication challenges and preferences among clinical trial participants in an under-resourced setting to improve adherence to study visits and participant retention

Background Ensuring protocol visit compliance and maintaining high participant retention remain critical elements of clinical trials. In the HVTN 702 HIV vaccine trial, Setshaba Research Centre in Soshanguve, Tshwane, South Africa, experienced challenges in communicating with participants to remind them about their study visits. In order to improve participants adhering to their study visits, and study retention, we aimed to identify challenges in mobile communication, and to establish preferences in communication methods and interest in receiving study information via cellphones. Methods We conducted a paper-based survey among HVTN 702 HIV vaccine trial participants at Setshaba Research Centre. The survey comprised of dichotomous and scale questions and was completed voluntarily and anonymously. The questions included those on their primary form of communication (calling, SMS and WhatsApp), the best time of day for the site to communicate with them, whether they were interested in receiving regular general study information updates via their cellular phone, how often they changed their cellular phones and/or network, whether they experienced any challenges with their cellular phones and what these challenges were, if any. All participants scheduled to visit the clinic from February to May 2019 were invited to participate. Thus, 90 of 380 (24%) participants enrolled by May 2019 were surveyed. Results The majority (68%) of participants were 26−35 years old and almost three-quarters (73%) were female. Almost all participants (99%) had a personal cellphone. Half of the participants experienced some challenge related to cellphones, these being poor network signal at home (12%), battery running flat frequently (11%), sharing their phone (9%), lack of data (9%), challenges with use of applications (6%) and their cellphones being unreliable (3%). Annually, 20% of participants made a single or multiple network changes. Communication preferences were calls by site staff (80%), SMS (16%) and WhatsApp (3%). Most preferred to be contacted in the morning (49%) or afternoon (31%). Site contact was rated as ‘very helpful’ (87%), and 97% were interested in receiving regular general study information updates via their cellphone. Conclusion Despite participants owning cellphones, there are still technical challenges, for example, network signals, battery-charging and applications. The majority of participants preferred being called rather than communicating by text messages or WhatsApp. Future studies need to include addressing participant challenges in maintaining contact and training of participants on use of cellphone applications to optimise communication. Noting the preferred time of day for participants to be called might improve the likelihood of making contact with them. The willingness to receive updates will aid in keeping participant interest high and enhance retention.

Young at risk-people in Maputo City, Mozambique, present a high willingness to participate in HIV trials: Results from an HIV vaccine preparedness cohort study

Introduction Vaccine efficacy testing requires engagement of willing volunteers with high disease incidence. We evaluated factors associated with willingness to participate in potential future HIV vaccine trials in Maputo, Mozambique. Methods Adults aged 18–35 years without HIV and who reported at least two sexual partners in the 3 months prior to screening were enrolled into a 24-month observational study. They were asked at screening and exit if they would be willing to participate in a theoretical HIV vaccine study. Bivariate and multivariate logistic regression analyses were done between willingness to participate, demographic, sexual behavior, and motivational factors for screening visit data. Logistic regression with generalized estimating equations (GEE) was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors potentially associated with willingness to participate for data from both visits. Results A total of 577 participants without HIV were eligible, including 275 (48%) women. The mean age was 22.2 (SD ± 3.9) years. At screening 529 (92%) expressed willingness to participate and the proportion remained stable at 378 (88%) of the 430 participants retained through the exit visit (p = 0.209). Helping the country (n = 556) and fear of needles (n = 26) were the top motive and barrier for willingness to participate, respectively. Results from the GEE binary logistic regression (screening visit and exit visit) showed that wanting to learn how to avoid risk behaviors (aOR 3.33, 95% CI: 1.61–6.86) and feeling protected against HIV infection (aOR 2.24, 95% CI: 1.07–4.7) were associated with willingness to participate in HIV vaccine studies. Conclusion The majority of our study population in Mozambique expressed willingness to participate in a theoretical HIV vaccine trial. Participation in a HIV vaccine trial was seen as a way to contribute to the fight against HIV but was associated with some unrealistic expectations such as protection against HIV. This reinforces the need for continuous mobilization and awareness of potential participants to HIV vaccine trial.

Participants’ characteristics and motivations to screen for HIV vaccine and monoclonal antibody trials in KwaZulu-Natal, South Africa

Background HIV is one of the greatest public health challenges in South Africa. Potential HIV vaccines and antibodies are thought to be cost-effective biomedical HIV prevention methods and are currently under investigation in phase I, II, and III trials. Consequently, current and future clinical trials need to ensure sufficient recruitment and retention. To achieve this goal, clinical trial staff need to understand the socio-demographic and behavioural characteristics of people volunteering to screen for these trials and their reasons for volunteering. Methods We conducted a secondary analysis of participant screening data across five vaccine and monoclonal antibody trials at four sites in KwaZulu-Natal, South Africa. Our study reviewed the demographic, behavioural, motivational, and health-related data from the case report forms and screening questionnaires. Descriptive statistics, chi-squared, and one-way ANOVA tests were used to analyse participants’ characteristics and motivation to participate in HIV vaccine and monoclonal antibody trials. Analyses were conducted using R version 3.5.2. Results Screening data from 1934 participants, including 79.2% of women, were obtained across all five trials (1034 enrolled, 900 screened out/declined). Screened participants predominately self-identified as black, heterosexual, cisgender women or men, many with lower educational backgrounds (43.9% did not complete secondary/high school), and several self-reported HIV-risk behaviours among themselves and their partners. 10.8% of the screened participants were living with HIV. Avoiding HIV risk was the main motivation to participate in clinical trials, followed by altruistic reasons such as a desire to help the community or helping to find a vaccine. Discussion The current recruitment approach of these trials attracts heterosexual participants who seek to reduce HIV risk and support their community. Hence, the data suggest the need for and potential acceptance of continued ongoing HIV prevention efforts. Current trials attract participants with lower educational levels, which may be driven by the site locations, current community mobilisation strategies and research site opening hours. The sites could consider more flexible working hours to accommodate working participants and find ways to connect participants to educational support and opportunities to upgrade education levels for the current clientele. Trial registration HVTN 100: A Safety and Immune Response Study of 2 Experimental HIV Vaccines, NCT02404311. Registered on March 17, 2015. HVTN 111: Safety and Immune Response to a Clade C DNA HIV Vaccine, NCT02997969. Registered on December 16, 2016. HVTN 108: Evaluating the Safety and Immunogenicity of HIV Clade C DNA Vaccine and MF59- or AS01B-Adjuvanted Clade C Env Protein Vaccines in Various Combinations in Healthy, HIV-Uninfected Adults, NCT02915016. Registered on September 22, 2016. HVTN 702: Pivotal Phase 2b/3 ALVAC/Bivalent gp120/MF59 HIV Vaccine Prevention Safety and Efficacy Study in South Africa, NCT02968849. Registered on November 1, 2016. HVTN 703/HPTN 081: Evaluating the Safety and Efficacy of the VRC01 Antibody in Reducing Acquisition of HIV-1 Infection in Women, NCT02568215. Registered on October 1, 2015.

Meeting report: South African Medical Research Council Standard of Care in Clinical Research in Low- And Middle-Income Settings Summit, November 2017

A cornerstone of HIV prevention clinical trials is providing a combination prevention package to all trial participants. The elements included in that standard of care (SoC) package evolve as new prevention modalities are developed. Pre-exposure prophylaxis (PrEP) was recommended by the World Health Organization for persons at high risk of acquiring HIV, but not all countries immediately adopted those recommendations. The South African Medical Research Council (SAMRC) convened a summit to discuss issues relating to SoC and PrEP in HIV prevention clinical trials taking place in lower- to middle-income countries (LMIC). Policymakers, regulators, ethicists, experts in law, researchers, representatives of advocacy groups, and the HIV Vaccine Trials Network (HVTN) presented a framework within which SoC principles could be articulated. A group of subject matter experts presented on the regulatory, ethical, scientific, and historic framework of SoC in clinical trials, focusing on PrEP in South Africa. Summit participants discussed how and when to include new HIV treatment and prevention practices into existing clinical guidelines and trial protocols, as well as the opportunities for and challenges to scaling up interventions. The summit addressed challenges to PrEP provision, such as inconsistent efficacy amongst different populations and various biological, virological, and immunological explanations for this heterogeneity. Advocates and community members propagated the urgent need for accessible interventions that could avert HIV infection. The meeting recommended supporting access to PrEP in HIV prevention trials by (1) developing PrEP access plans for HIV vaccine trials, (2) creating a PrEP fund that would supply PrEP to sites conducting HIV prevention trials via a central procurement mechanism, and (3) supporting the safety monitoring of PrEP. This report summarizes the presentations and discussions from the summit in order to highlight the importance of SoC in HIV prevention clinical trials.