Development of liposome-based freeze-dried rods for vaginal vaccine delivery against HIV-1

The present investigation deals with development and characteriza- tion of the liposomes-based freeze-dried rods for the vaginal delivery of gp140 antigen in mice. Positively charged, negatively charged and neutral liposomes were prepared and characterized for various parameters e.g. morphology, size, polydispersity index, zeta potential and antigen encapsulation efficiency. To further improve the efficacy of vaccine delivery, antigen encapsulated liposomes were formulated as polymer gel-based freeze-dried rods, which were then characterized for moisture content. The redispersibility of the liposomes-based freeze- dried rods was determined in simulated vaginal fluid and liposome gel was investigated for mucoadhesion. The developed liposome-based freeze-dried rods systems could offer potential as stable and practical dosage form for the mucosal immunization against HIV-1 infection

JACK trial protocol: a phase III multicentre cluster randomised controlled trial of a school-based relationship and sexuality education intervention focusing on young male perspectives.

INTRODUCTION: Teenage pregnancy remains a worldwide health concern which is an outcome of, and contributor to, health inequalities. The need for gender-aware interventions with a focus on males in addressing teenage pregnancy has been highlighted as a global health need by WHO and identified in systematic reviews of (relationship and sexuality education (RSE)). This study aims to test the effectiveness of an interactive film-based RSE intervention, which draws explicit attention to the role of males in preventing an unintended pregnancy by reducing unprotected heterosexual teenage sex among males and females under age 16 years. METHODS AND ANALYSIS: A phase III cluster randomised trial with embedded process and economic evaluations. If I Were Jack encompasses a culturally sensitive interactive film, classroom materials, a teacher-trainer session and parent animations and will be delivered to replace some of the usual RSE for the target age group in schools in the intervention group. Schools in the control group will not receive the intervention and will continue with usual RSE. Participants will not be blinded to allocation. Schools are the unit of randomisation stratified per country and socioeconomic status. We aim to recruit 66 UK schools (24 in Northern Ireland; 14 in each of England, Scotland and Wales), including approximately 7900 pupils. A questionnaire will be administered at baseline and at 12-14 months postintervention. The primary outcome is reported unprotected sex, a surrogate measure associated with unintended teenage pregnancy. Secondary outcomes include knowledge, attitudes, skills and intentions relating to avoiding teenage pregnancy in addition to frequency of engagement in sexual intercourse, contraception use and diagnosis of sexually transmitted infections. ETHICS AND DISSEMINATION: Ethical approval was obtained from Queen's University Belfast. Results will be published in peer-reviewed journals and disseminated to stakeholders. Funding is from the National Institute for Health Research. TRIAL REGISTRATION NUMBER: ISRCTN99459996

Can Teenage Men Be Targeted to Prevent Teenage Pregnancy? A Feasibility Cluster Randomised Controlled Intervention Trial in Schools.

The World Health Organisation advocates a direct focus on adolescent men in reducing adolescent pregnancy; however, no trials have been conducted. This trial (ISRCTN11632300; NCT02092480) determines whether a novel Relationship and Sexuality Educational intervention, If I Were Jack, is acceptable and feasible to implement in mixed sex UK classrooms. The intervention is a teacher-delivered intervention that emphasises male alongside female  responsibility in preventing unintended pregnancies and is designed to prevent unprotected sex. The trial was a parallel-group cluster randomised controlled feasibility trial with embedded process and cost evaluation in eight secondary schools (unit of randomisation) among 831 pupils (mean age 14) in Northern Ireland, alongside a qualitative evaluation of transferability in ten schools in Scotland, Wales and England. The sampling strategy was a maximum variation quota sample designed to capture a range of school management types. Four schools were randomised to each arm and the control arm continued with usual practice. Study duration was 12 months (from November 2014), with follow-up 9 months post-baseline. Results demonstrated that the intervention was acceptable to schools, pupils and teachers, and could be feasibly implemented, cost-effectively, with minor enhancements. The between-group difference in incidence of unprotected sex (primary outcome at pupil level) of 1.3% (95% CI 0.5-2.2) by 9 months demonstrated a potential effect size consistent with those reported to have had meaningful impact on teenage pregnancy. The study responds to global health policy for a paradigm shift towards inclusion of men in the achievement of sexual and reproductive health goals in a practical way by demonstrating that a gender-sensitive as well as a gender transformative intervention targeting males to prevent teenage pregnancy is acceptable to adolescent men and women and implementable in formal education structures. If I Were Jack now merits further effectiveness testing

Microneedle mediated intradermal delivery of adjuvanted recombinant HIV-1 CN54gp140 effectively primes mucosal boost inoculations

AbstractDissolving polymeric microneedle arrays formulated to contain recombinant CN54 HIVgp140 and the TLR4 agonist adjuvant MPLA were assessed for their ability to elicit antigen-specific immunity. Using this novel microneedle system we successfully primed antigen-specific responses that were further boosted by an intranasal mucosal inoculation to elicit significant antigen-specific immunity. This prime-boost modality generated similar serum and mucosal gp140-specific IgG levels to the adjuvanted and systemic subcutaneous inoculations. While the microneedle primed groups demonstrated a balanced Th1/Th2 profile, strong Th2 polarization was observed in the subcutaneous inoculation group, likely due to the high level of IL-5 secretion from cells in this group. Significantly, the animals that received a microneedle prime and intranasal boost regimen elicited a high level IgA response in both the serum and mucosa, which was greatly enhanced over the subcutaneous group. The splenocytes from this inoculation group secreted moderate levels of IL-5 and IL-10 as well as high amounts of IL-2, cytokines known to act in synergy to induce IgA. This work opens up the possibility for microneedle-based HIV vaccination strategies that, once fully developed, will greatly reduce risk for vaccinators and patients, with those in the developing world set to benefit most