Future Vaccine Trials Research Articles

The Influence of Bacille Calmette-Guérin Vaccine Strain on the Immune Response against Tuberculosis

Approximately 100 million doses of bacille Calmette-Guérin (BCG) vaccine are given each year to protect against tuberculosis (TB). More than 20 genetically distinct BCG vaccine strains are in use worldwide. Previous studies suggest that BCG vaccine strain influences the immune response and protection against TB. Current data on which BCG vaccine strain induces the optimal immune response in humans are insufficient. To compare the immune response to three different BCG vaccine strains given to infants at birth. Newborn infants in a tertiary women's hospital were immunized at birth with one of three BCG vaccine strains. A stratified randomization according to the mother's region of birth was used. The presence of mycobacterial-specific polyfunctional CD4 T cells measured by flow cytometry 10 weeks after immunization. Of the 209 infants immunized, data from 164 infants were included in the final analysis (BCG-Denmark, n = 54; BCG-Japan, n = 54; BCG-Russia, n = 57). The proportion of polyfunctional CD4 T cells was significantly higher in infants immunized with BCG-Denmark (0.013%) or BCG-Japan (0.016%) than with BCG-Russia (0.007%) (P = 0.018 and P = 0.003, respectively). Infants immunized with BCG-Japan had higher concentrations of secreted Th1 cytokines; infants immunized with BCG-Denmark had higher proportions of CD107-expressing cytotoxic CD4 T cells. There are significant differences in the immune response induced by different BCG vaccine strains in newborn infants. Immunization with BCG-Denmark or BCG-Japan induced higher frequencies of mycobacterial-specific polyfunctional and cytotoxic T cells and higher concentrations of Th1 cytokines. These findings have potentially important implications for global antituberculosis immunization policies and future tuberculosis vaccine trials.

Atlantic halibut experimentally infected with nodavirus shows increased levels of T-cell marker and IFNγ transcripts

The transcript levels of viral RNAs, selected T-cell marker and cytokine genes, toll like receptor (TLR) 7, and two interferon stimulated genes (ISG) were analysed in sexually immature adult Atlantic halibut (Hippoglossus hippoglossus L.) experimentally infected with nodavirus. The expression of the T-cell markers, TLR7 and the cytokine genes was further explored in in vitro stimulated anterior kidney leucocytes (AK leucocytes) isolated from the experiment fish and from additional untreated non-injected fish. The levels of viral RNA1 and RNA2 were increasing in brain and eye at around 4 and 8weeks post injection (wpi), respectively, and still increasing at the end of the experiment, especially in eye. Immuno-positive cells and signs of vacuolisation in both brain and eye were seen at 14wpi. Increased transcript levels of TCRβ, CD4-2, CD4, CD8α, and Lck in brain and eye of the experimentally infected halibut suggested an involvement of halibut T-cells in the immune response against nodavirus. Interestingly, a similar expression pattern of TCRβ, CD4 and Lck was seen in both brain and eye. However, compared to brain that showed elevated transcript levels of TCRβ, CD4 and Lck mainly at 10 and 14wpi, the increase appeared earlier between 3 and 4wpi in the eye. Yet, an increase in the transcript level of IFNγ was seen at 10 and 14wpi in both organs. Moreover, elevated levels of TLR7, IL-1β, IL-6, ISG15 and Mx were detected in vivo. The in vitro experiments, stimulating AK leucocytes with ConA–PMA, imiquimod or nodavirus, further supported an involvement of IL-6 and IFNγ in the immune response against nodavirus and the involvement of CD8β+ cells. Results from the present study thus indicate an importance of T-cells, IFNγ and the analysed ISGs in the immune response against nodavirus in Atlantic halibut, and would be of great help in future vaccination trials giving the possibility to monitor the immune response rather than mortality during post-vaccination challenge experiments.

Adolescents' Understanding of Research Concepts

To identify ways to improve adolescents' understanding of informed assent by exploring adolescent comprehension of concepts common to all clinical trials as well as those specific to a human immunodeficiency virus vaccine trial. Qualitative descriptive study. Community-based organizations. Healthy adolescents aged 15 to 17 years in 8 focus groups. Focus groups were conducted using a semistructured interview guide. Digital recordings of the groups were transcribed verbatim. Textual data were categorized by 2 investigators using directed qualitative content analysis techniques. Major themes and subthemes were identified, and representative quotes were selected. The general research concepts that were most difficult for teens to understand were placebo and randomization. The most difficult vaccine trial concepts were how a vaccine works and that a vaccine is used for prevention rather than treatment. The most difficult human immunodeficiency virus vaccine-specific trial concept was that standard human immunodeficiency virus antibody tests might provide a false-positive result for participants receiving the test vaccine. Focus group participants wanted to be informed about adverse effects, trial procedures, and whether previous research had been performed before making a decision about trial participation. Many clinical trial concepts were difficult for teens to understand. Attention needs to be directed toward developing effective ways to explain these concepts to adolescents participating in future human immunodeficiency virus vaccine and other clinical trials.

Abstract 5534: Evaluation of clinical safety and immunogenicity of DPX-0907, a multi-epitope vaccine for the treatment of breast, ovarian and prostate cancers

Abstract A successful cancer vaccine needs to overcome tumor-induced immune suppression while enhancing protective Type1-biased tumor-specific immune responses. To achieve this, enhanced vaccine delivery technologies are needed. We have developed a novel liposome-in-oil depot vaccine platform called DepoVaxTM (DPX) which increases the potency of peptide-based cancer vaccines and elicits a strong cytotoxic T cell response. DPX-0907 is a human DPX-based vaccine containing 7 HLA-A2 restricted peptides and is indicated for breast, ovarian and prostate cancer. The antigens were carefully selected with a multi-targeted approach that focuses on proteins involved in pathways that are critical for the survival of a cancer cell. This reduces the likelihood of immune escape through loss of antigen expression/presentation as a tumor responds to vaccine-induced immune pressure. We recently showed that DPX-0907 produces stronger and better sustained immune responses in HLA-A2 transgenic mice than a GM-CSF/ emulsion vaccine. A multicenter phase I clinical trial was initiated in five US clinical sites in March 2010 to evaluate the safety and immunogenicity of DPX-0907 in patients with advanced breast, ovarian or prostate cancer. The open label, dose escalation study recruited patients into one of 2 dose levels (0.25 mL and 1 mL). The vaccine was administered subcutaneously every three weeks for a total of three vaccinations. PBMC's were collected prior to each vaccination and at three time points following the last vaccination. These samples were also used to monitor the immunosuppressive MDSC population in patients receiving the vaccine treatment. In addition, immune monitoring of vaccine-induced responses is based on multi-parametric intracellular cytokine staining of multiple immune cell types and the functional analysis of peptide-MHC-multimer positive CD8 T cells. This first- in-man trial has generated important safety information that support the use of DepoVax for delivering multi-peptide based vaccines. The extensive immune monitoring will aid in the rational design of future DPX-0907 and other DepoVax-based vaccine trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5534. doi:10.1158/1538-7445.AM2011-5534

Communication, recruitment and enrolment in the preventative and therapeutic phase I clinical trial against HIV/AIDS based on the recombinant HIV-1 Tat protein

The role of volunteer recruitment in HIV vaccine trials has recently been considered particularly with respect to critical issues, such as motivation, psychological assessment and social impact. The preventative and therapeutic phase I trials based on the recombinant biologically active Tat vaccine candidate, sponsored in Italy by the Istituto Superiore di Sanità, included a specific centralised procedure (SCP) developed to support both the sponsor and the volunteers during trial enrolment and conduction. This process, which is an integrated, multidisciplinary, biomedical and psycho-socio-behavioural network, represented a novel and important aspect for the conduction and success of the clinical study. A specific flow of information from the sponsor to the population was developed through the SCP which started from the national announcement of the trials (through a press conference and a press release) to the enrolment of the volunteers. To this aim a telephone counselling intervention was performed to supply the scientific information translated in personalised message, allowing to select potential participants prior to the first contact with the clinical sites. Furthermore, the multi-step procedure contributed in reinforcing the motivation to participation and trial retention, providing important hints for the design of standardised enrolment procedures to be used in clinical studies. Indeed, this methodological approach, which foresees the joined participation of researchers and expert of communication, could be followed in future vaccine trials in order to improve the effectiveness of enrolment procedures.

HIV vaccine trial willingness among injection and non-injection drug users in two urban centres, Barcelona and San Francisco

Being able to recruit high-risk volunteers who are also willing to consider future participation in vaccine trials are critical features of vaccine preparedness studies. We described data from two cohorts of injection- and non-injection drug users in Barcelona, Spain [Red Cross centre] and in San Francisco, USA, [UFO-VAX study] at high risk of HIV/HCV infection to assess behaviour risk exposure and willingness to participate in future preventive HIV vaccine trials. We successfully identified drug-using populations that would be eligible for future HIV vaccine efficacy trials, based on reported levels of risk during screening and high levels of willingness to participate. In both groups, Red Cross and UFO-VAX respectively, HCV infection was highly prevalent at baseline (41% and 34%), HIV baseline seroprevalence was 4.2% and 1.5%, and high levels of willingness were seen (83% and 78%).

Effect of schistosoma infection on malaria immune response: A systematic review

Executive Summary Background Worldwide an estimated 225 million cases and about 800, 000 deaths due to malaria were documented in 2009. Malaria vaccines have been developed as a malaria control strategy. Immune response to these vaccines might be affected by the blood fluke schistosoma which is often co-endemic with malaria in Sub-Saharan Africa where most of phase II and Phase III malaria vaccine trials were conducted. Objectives To systematically search, appraise and synthesize the best available evidence on the effect of schistosoma infection on the immune response to malaria antigens and provide direction to future malaria vaccination trials. Types of participants The review considered studies with above 5 year old individuals as participants. Phenomenon of interest The phenomenon of interest was the presence of schistosoma infection Types of outcomes Blood serum levels of Th1 and Th2 specific to Merozoite Surface Proteins 1, 2, and 3 of malaria were considered as primary outcomes. While blood serum levels of IgG1, IgG2, IgG3, IFN-γ, IL-10 and TGF-β directed against Merozoite Surface Proteins were considered as secondary outcomes. Types of studies Studies with any quantitative study designs were considered for inclusion. Search Strategy Any quantitative English language articles published between 1994 and April 2011 were sought using a comprehensive search strategy. Assessment of methodological quality It was done using Joanna Briggs Institutes' Meta Analysis of Statistical Assessment and Review Instrument critical appraisal tools. Data extraction Data extraction was carried out using the Joanna Briggs Institute Meta Analysis of Statistical Assessment and Review Instrument data extraction tool. Data synthesis Meta- analysis was conducted using random effects model with an inverse variance method with RevMan5 software. Heterogeneity between the studies was assessed using ξ2 test at a p-value of <0.1. Summary statistics were expressed as Standardized Mean Difference with 95% confidence intervals at a p-value of <0.05. Results From 3985 titles identified during the initial search, 3 cohort studies were included in the review following detailed examination and critical appraisal. Mean blood serum level of IgG1 directed against MSP of malaria was increased in S.hematobium positive individuals than in schistosoma negative individuals (0.478 and 0.181). This effect was small with no statistical significance, SMD (95% CI), 0.15 (-2.00, 2.31), p=0.89. Similarly a small and statistically not significant increase in mean blood serum levels of IgG3 and IFN-γ directed against MSP of malaria were found in schistosoma positive individuals than in schistosoma negative individuals with a SMD (95% CI) of 0.31 (-0.66, 1.29), p=0.52 and 0.16 (-0.27, 0.59), p=0.46, respectively. Conclusions Implications for Practice Concurrent schistosoma infection increases humoral immune response measures to malaria. This could confound an increase in humoral immune response measures after the administration of malaria vaccine. In addition, it might increase the incidence of malaria complication such as cerebral malaria by increasing IFN-γ levels. Implications for Research Further longitudinal studies aimed at determining the difference in long term response (cellular immunity) to malaria vaccine in individuals with and without schistosoma infection need to be undertaken.

“Once Bitten, Twice Shy”: Participant perspectives in the aftermath of an early HIV vaccine trial termination

The Step Study phase IIb HIV-1 vaccine trial was terminated early due to futility; subsequent analyses revealed increased susceptibility to HIV infection among a subset of test vaccine recipients. We conducted a mixed methods investigation, including a brief, self-administered baseline questionnaire and in-depth, semi-structured, 1-h interviews after unblinding, to explore experiences and perspectives among trial participants and key informants. Interviews were digitally recorded, transcribed, and analyzed using NVivo and thematic techniques. Forty-eight trial participants (46 gay/bisexual men) completed baseline surveys; 15 (14 gay/bisexual men) engaged in post-trial interviews. Participants indicated surprise and disappointment about the early trial termination and unexpected risks. Some articulated understanding the uncertainties of clinical trials, steadfast support and willingness to participate in the future; others reported greater risks than they deemed acceptable and unlikelihood of volunteering again. A few indicated mistrust of trial sponsors and ethics. Participants’ most profound criticism was not about unexpected results, but perceived delays in unblinding and gaps in post-trial dissemination of information. Future HIV vaccine trials may benefit from increased emphasis on: (1) communication mechanisms among participants, investigators and trial sponsors, and (2) post-trial dissemination of information and psychosocial support.

HIV vaccines: lessons learned and the way forward

An effective HIV vaccine is a global health priority. We describe lessons learned from four HIV vaccine trials that failed to demonstrate efficacy and one that showed modest protection as a pathway forward. The Merck Ad5 phase IIb T-cell vaccine failed to show efficacy and might have increased the risk of HIV acquisition in men who have sex with men. Although VaxGen gp120 alone was not efficacious in groups at high risk for HIV-1 infection, the RV144 ALVAC prime and gp120 boost regimen showed 31% efficacy in low-incidence heterosexuals. All trials demonstrated the limitations of available laboratory and animal models to assess relevant vaccine-induced immune responses and predict clinical trial outcome. Analysis of innate and adaptive responses induced in RV144 will guide future trial design. Future HIV vaccine trials should define the RV144 immune responses relevant to protection, improve durability and level of protection, and assess efficacy in diverse risk groups. New strategies examining heterologous vector prime-boost, universal inserts, replicating vectors, and novel protein or adjuvant immunogens should be explored to induce T-cell and antibody responses. HIV vaccine development requires innovative ideas and a sustained long-term commitment of scientists, governments, and the community.

Health education through analogies: preparation of a community for clinical trials of a vaccine against hookworm in an endemic area of Brazil.

BackgroundObtaining informed consent for clinical trials is especially challenging when working in rural, resource-limited areas, where there are often high levels of illiteracy and lack of experience with clinical research. Such an area, a remote field site in the northeastern part of the state of Minas Gerais, Brazil, is currently being prepared for clinical trials of experimental hookworm vaccines. This study was conducted to assess whether special educational tools can be developed to increase the knowledge and comprehension of potential clinical trial participants and thereby enable them to make truly informed decisions to participate in such research.Methodology/Principal FindingsAn informational video was produced to explain the work of the research team and the first planned hookworm vaccine trial, using a pedagogical method based on analogies. Seventy-two adults living in a rural community of Minas Gerais were administered a structured questionnaire that assessed their knowledge of hookworm, of research and of the planned hookworm vaccine trial, as well as their attitudes and perceptions about the researchers and participation in future vaccine trials. The questionnaire was administered before being shown the educational video and two months after and the results compared. After viewing the video, significant improvements in knowledge related to hookworm infection and its health impact were observed: using a composite score combining related questions for which correct answers were assigned a value of 1 and incorrect answers a value of 0, participants had a mean score of 0.76 post-video compared to 0.68 pre-video (p = 0.0001). Similar improvements were seen in understanding the purpose of vaccination and the possible adverse effects of an experimental vaccine. Although 100% of participants expressed a positive opinion of the researchers even before viewing the film and over 90% said that they would participate in a hookworm vaccine trial, an increase in the number who expressed fear of being vaccinated with a novel vaccine was seen after viewing the video (51.4% post-video versus 29.2% pre-video). Increases were also seen in the proportion who thought that participation in a vaccine trial would be inconvenient or disrupt their daily activities.Conclusions/SignificanceEven in rural, resource-limited populations, educational tools can be specially designed that significantly improve understanding and therefore the likelihood of obtaining truly informed consent for participation in clinical research. The observed changes in the knowledge and perceptions of the research participants about hookworm infection and the experimental hookworm vaccine demonstrate that the video intervention was successful in increasing understanding and that the subjects acquired knowledge pertinent to the planned research.

HIV infection awareness and willingness to participate in future HIV vaccine trials across different risk groups in Abuja, Nigeria

The purpose of this survey is to generate baseline data on the level of HIV infection awareness and willingness to participate (WTP) in hypothetical vaccine trials, ahead of any trial conduct in Nigeria. In a cross-sectional survey, 500 respondents were interviewed, including sex workers, male motorcycle taxi drivers, students, and the general public. About 153 (30.6%) of the respondents did not believe that correct and consistent use of condom can protect people from getting HIV, while about 66 (13.2%) respondents believed it is possible to get HIV by sharing meal with an infected person. Population groups considered at high risk for HIV were less aware of the disease, however, they were more willing to participate in HIV vaccine trials compared those at low risk of the disease. A total of 55% expressed WTP in a hypothetical vaccine trial after they were informed about it. Age, population group, and ethnicity were significantly associated with WTP.

A randomized trial of enhanced HIV risk-reduction and vaccine trial education interventions among HIV-negative, high-risk women who use noninjection drugs: the UNITY study.

Limited data are available on interventions to reduce sexual risk behaviors and increase knowledge of HIV vaccine trial concepts in high-risk populations eligible to participate in HIV vaccine efficacy trials. The UNITY Study was a 2-arm randomized trial to determine the efficacy of enhanced HIV risk-reduction and vaccine trial education interventions to reduce the occurrence of unprotected vaginal sex acts and increase HIV vaccine trial knowledge among 311 HIV-negative noninjection drug using women. The enhanced vaccine education intervention using pictures along with application vignettes and enhanced risk-reduction counseling consisting of 3 one-on-one counseling sessions were compared with standard conditions. Follow-up visits at 1 week and 1, 6, and 12 months after randomization included HIV testing and assessment of outcomes. During follow-up, the percent of women reporting sexual risk behaviors declined significantly but did not differ significantly by study arm. Knowledge of HIV vaccine trial concepts significantly increased but did not significantly differ by study arm. Concepts about HIV vaccine trials not adequately addressed by either condition included those related to testing a vaccine for both efficacy and safety, guarantees about participation in future vaccine trials, assurances of safety, medical care, and assumptions about any protective effect of a test vaccine. Further research is needed to boost educational efforts and strengthen risk-reduction counseling among high-risk noninjection drug using women.

Dendritic Cell-Derived Exosomes for Cancer Immunotherapy: What's Next?

Exosomes are nanovesicles originating from late endosomal compartments and secreted by most living cells in ex vivo cell culture conditions. The interest in exosomes was rekindled when B-cell and dendritic cell-derived exosomes were shown to mediate MHC-dependent immune responses. Despite limited understanding of exosome biogenesis and physiological relevance, accumulating evidence points to their bioactivity culminating in clinical applications in cancer. This review focuses on the preclinical studies exploiting the immunogenicity of dendritic cell-derived exosomes (Dex) and will elaborate on the past and future vaccination trials conducted using Dex strategy in melanoma and non-small cell lung cancer patients.

Using Social Networks to Recruit an HIV Vaccine Preparedness Cohort

To evaluate a social network approach to develop an adolescent cohort for HIV vaccine preparedness and investigate characteristics that influence recruitment. We summarize baseline data from a prospective cohort study that included 4 sessions over 6 months. Fifty-nine HIV-infected adolescent and adult patients of a family-based HIV clinic named significant others and indicated willingness to involve them in this study. Sixty-two adolescent and adult significant others not known to be HIV infected were enrolled. Logistic regression was used to estimate factors associated with willingness. Participants identified 624 social network members including 276 adolescents (44%). Network member's awareness of the index's HIV positivity (P < 0.01) and older age (P = 0.05) affected willingness. Respondents were less willing to invite drug-risk alters (P = 0.006). Adolescents were willing to invite more adolescents than were adults (P < 0.0001). Adolescents younger than 18 years old reported fewer sexual and drug-using risk behaviors than expected. HIV-infected patients are willing to recruit their social networks, provided concerns about disclosure of HIV status are addressed. Using social networks to identify and recruit adolescent populations is appropriate and feasible for vaccine preparedness activities, future vaccine trials, and other prevention programs, but procedures are needed to selectively identify and retain high-risk youth.

Clinical, Parasitologic, and Immunologic Evolution in Dogs Experimentally Infected with Sand Fly-Derived Leishmania chagasi Promastigotes

Experimental infection of dogs with Leishmania infantum has yielded heterogeneous clinical, parasitologic, and immunologic results. We studied dogs infected with 10(5) or 10(4) sand fly-derived promastigotes delivered by the intradermal (ID) or intravenous (IV) routes. Total mortality over 1 year post-infection reached 23.8%. The mortality and proportion of sustained polysymptomatic dogs was highest in the IV-10(5) group. The early appearance of polysymptoms was associated with an increased risk of progression to death. Dissemination of the parasite to lymph nodes was faster, and the subsequent infectivity to sand flies higher, in the IV compared with ID-infected dogs. Parasite-specific IgG1 or IgG2 production was similar among the groups, but higher interferon-gamma (IFN-gamma) and interleukin-10 (IL-10) expression was associated with polysymptomatic dogs. On the basis of the data obtained from this study, a sample size analysis using different endpoints for future vaccine trials is described.

Short Communication: HIV Type 1 Genetic Diversity among Tea Plantation Workers in Kericho, Kenya

In preparation for HIV-1 vaccine trials in Kenya, 2801 study volunteers, from a tea plantation in Kericho, were recruited as part of a prospective vaccine cohort development study. Cryopreserved plasma was available from 401 HIV-positive volunteers, and was the source of viral RNA for genotyping by the multiregion hybridization assay (MHA). Logistic regression was performed to determine association of risk factors and HIV-1 recombinant and dual infections. At baseline, HIV-1 subtype A was the dominant circulating pure subtype (56%), followed by subtype D (10%) and C (5%). Recombinant HIV-1 strains accounted for almost one-third of all infections (29%), with 7% infected with a dual strain of the HIV-1 variants described. A higher number of HIV-1 recombinant and dual infections was observed among volunteers who were 18-24 and 25-29 years of age, affiliated with the Luo tribe, had been married two or more times, reported not being circumcised, and had STI symptoms in the past 6 months. Adjusted odds ratios (AOR) significantly associated with HIV-1 recombinant and dual infection were age difference from current spouse (5-9 years; AOR = 2.5, 95% CI = 1.2-5.3 and > or = 10 years; AOR = 3.1, 95% CI = 1.5-6.4) and reported STI symptoms in the past 6 months (AOR = 4.8, 95% CI = 2.0-11.6), respectively. In conclusion, our results suggest that there is considerable heterogeneity with respect to HIV-1 subtype diversity in this population that should be considered in the planning for future vaccine trials in the region.

Differential Specificity and Immunogenicity of Adenovirus Type 5 Neutralizing Antibodies Elicited by Natural Infection or Immunization

A recent clinical trial of a T-cell-based AIDS vaccine delivered with recombinant adenovirus type 5 (rAd5) vectors showed no efficacy in lowering viral load and was associated with increased risk of human immunodeficiency virus type 1 (HIV-1) infection. Preexisting immunity to Ad5 in humans could therefore affect both immunogenicity and vaccine efficacy. We hypothesized that vaccine-induced immunity is differentially affected, depending on whether subjects were exposed to Ad5 by natural infection or by vaccination. Serum samples from vaccine trial subjects receiving a DNA/rAd5 AIDS vaccine with or without prior immunity to Ad5 were examined for the specificity of their Ad5 neutralizing antibodies and their effect on HIV-1 immune responses. Here, we report that rAd5 neutralizing antibodies were directed to different components of the virion, depending on whether they were elicited by natural infection or vaccination in HIV vaccine trial subjects. Neutralizing antibodies elicited by natural infection were directed largely to the Ad5 fiber, while exposure to rAd5 through vaccination elicited antibodies primarily to capsid proteins other than fiber. Notably, preexisting immunity to Ad5 fiber from natural infection significantly reduced the CD4 and CD8 cell responses to HIV Gag after DNA/rAd5 vaccination. The specificity of Ad5 neutralizing antibodies therefore differs depending on the route of exposure, and natural Ad5 infection compromises Ad5 vaccine-induced immunity to weak immunogens, such as HIV-1 Gag. These results have implications for future AIDS vaccine trials and the design of next-generation gene-based vaccine vectors.

P15-25. Preparation for HIV vaccine trials in Africa: barriers and facilitators for the establishment of a community advisory board in Burkina Faso

Background Involvement of community level stakeholders in the future HIV vaccine trials is essential to ensure that rights, views, concerns, needs and expectations of the target population are fully taken into account in all phases of their implementation. We carried out a multicomponent situation analysis in two future urban sites in Burkina Faso to identify the proper way to setting up a CAB competent to accompany the trials.

P14-04. HIV-SELECTEST EIA and rapid test: a novel assay for differential diagnosis of HIV infections in the face of vaccine-generated antibodies

Background All current human immunodeficiency virus (HIV) vaccine candidates contain multiple viral components and elicit antibodies that react positively in licensed HIV diagnostic tests. Thus, vaccine trial participants could be falsely diagnosed as infected with HIV and it is a major public health concern for volunteers who want to participate in future HIV vaccine trials. Additionally, uninfected, seropositive vaccinees may encounter long-term social and economic harms. Moreover, this also interferes with early detection of true HIV infections during preventive HIV vaccine trials. Based on the increased number of HIV vaccines being tested globally, it is essential to differentiate vaccine – from virus-induced antibodies.

Criteria for the differentiation between young and old Onchocerca volvulus filariae

Drugs exist that show long-lasting inhibition of embryogenesis and microfilaria production or macrofilaricidal activity against Onchocerca volvulus. Therefore, the patients have to be followed-up for several years. Clinical drug trials have to be performed in areas with ongoing transmission to assess the efficacy on younger worms. In addition, future vaccine trials may also require demonstrating efficacy against establishment of new worms. For the evaluation of the efficacy, it is necessary to differentiate between older worms, which were exposed to the drug, and younger worms newly acquired after drug treatment or vaccination. Here, we describe criteria for the differentiation between young and old filariae based on histological studies of worms with a known age from travellers, or from children, or patients living in areas with interrupted transmission in Burkina Faso, Ghana or Uganda. Older worms were larger and presented degenerated tissues. Gomori's iron stain showed that the worms accumulated more iron with increasing age, first in the gut and later in other organs. Using an antibody against O. volvulus lysosomal aspartic protease, the gut of young worms was stained only weakly; whereas, it was stronger labelled in older worms, accompanied by additional staining of hypodermis and epithelia. Using morphological and immunohistological criteria, it was possible to differentiate young (1–3 years old) from older females and to identify young males.