Study protocol for a phase 1/2, single-centre, double-blind, double-dummy, randomized, active-controlled, age de-escalation trial to assess the safety, tolerability and immunogenicity of a measles and rubella vaccine delivered by a microneedle patch in healthy adults (18 to 40 years), measles and rubella vaccine-primed toddlers (15 to 18 months) and measles and rubella vaccine-naïve infants (9 to 10 months) in The Gambia [Measles and Rubella Vaccine Microneedle Patch Phase 1/2 Age De-escalation Trial].

BACKGROUND: New strategies to increase measles and rubella vaccine coverage, particularly in low- and middle-income countries, are needed if elimination goals are to be achieved. With this regard, measles and rubella vaccine microneedle patches (MRV-MNP), in which the vaccine is embedded in dissolving microneedles, offer several potential advantages over subcutaneous delivery. These include ease of administration, increased thermostability, an absence of sharps waste, reduced overall costs and pain-free administration. This trial will provide the first clinical trial data on MRV-MNP use and the first clinical vaccine trial of MNP technology in children and infants. METHODS: This is a phase 1/2, randomized, active-controlled, double-blind, double-dummy, age de-escalation trial. Based on the defined eligibility criteria for the trial, including screening laboratory investigations, 45 adults [18-40 years] followed by 120 toddlers [15-18 months] and 120 infants [9-10 months] will be enrolled in series. To allow double-blinding, participants will receive either the MRV-MNP and a placebo (0.9% sodium chloride) subcutaneous (SC) injection or a placebo MNP and the MRV by SC injection (MRV-SC). Local and systemic adverse event data will be collected for 14 days following study product administration. Safety laboratories will be repeated on day 7 and, in the adult cohort alone, on day 14. Unsolicited adverse events including serious adverse events will be collected until the final study visit for each participant on day 180. Measles and rubella serum neutralizing antibodies will be measured at baseline, on day 42 and on day 180. Cohort progression will be dependent on review of the unblinded safety data by an independent data monitoring committee. DISCUSSION: This trial will provide the first clinical data on the use of a MNP to deliver the MRV and the first data on the use of MNPs in a paediatric population. It will guide future product development decisions for what may be a key technology for future measles and rubella elimination. TRIAL REGISTRATION: Pan-African Clinical Trials Registry 202008836432905 . CLINICALTRIALS: gov NCT04394689

Trapping \u3ci\u3ePhyllophaga \u3c/i\u3espp. (Coleoptera: Scarabaeidae: Melolonthinae) in the United States and Canada using sex attractants.

The sex pheromone of the scarab beetle, Phyllophaga anxia, is a blend of the methyl esters of two amino acids, L-valine and L-isoleucine. A field trapping study was conducted, deploying different blends of the two compounds at 59 locations in the United States and Canada. More than 57,000 males of 61 Phyllophaga species (Coleoptera: Scarabaeidae: Melolonthinae) were captured and identified. Three major findings included: (1) widespread use of the two compounds [of the 147 Phyllophaga (sensu stricto) species found in the United States and Canada, males of nearly 40% were captured]; (2) in most species intraspecific male response to the pheromone blends was stable between years and over geography; and (3) an unusual pheromone polymorphism was described from P. anxia. Populations at some locations were captured with L-valine methyl ester alone, whereas populations at other locations were captured with L-isoleucine methyl ester alone. At additional locations, the L-valine methyl ester-responding populations and the L-isoleucine methyl ester-responding populations were both present, producing a bimodal capture curve. In southeastern Massachusetts and in Rhode Island, in the United States, P. anxia males were captured with blends of L-valine methyl ester and L-isoleucine methyl ester

Volunteers’ Support of Carers of Rural People Living with Dementia to Use a Custom-Built Application

There is great potential for human-centred technologies to enhance wellbeing for people living with dementia and their carers. The Virtual Dementia Friendly Rural Communities (Verily Connect) project aimed to increase access to information, support, and connection for carers of rural people living with dementia, via a co-designed, integrated website/mobile application (app) and Zoom videoconferencing. Volunteers were recruited and trained to assist the carers to use the Verily Connect app and videoconferencing. The overall research design was a stepped wedge open cohort randomized cluster trial involving 12 rural communities, spanning three states of Australia, with three types of participants: carers of people living with dementia, volunteers, and health/aged services staff. Data collected from volunteers (n = 39) included eight interviews and five focus groups with volunteers, and 75 process memos written by research team members. The data were analyzed using a descriptive evaluation framework and building themes through open coding, inductive reasoning, and code categorization. The volunteers reported that the Verily Connect app was easy to use and they felt they derived benefit from volunteering. The volunteers had less volunteering work than they desired due to low numbers of carer participants; they reported that older rural carers were partly reluctant to join the trial because they eschewed using online technologies, which was the reason for involving volunteers from each local community

Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure

<div><p>Andes virus (ANDV) and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS) cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgYΔFc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA) for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA₈₀ titers >100,000). Analysis of IgY and IgYΔFc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. α-ANDV immune sera, or IgY/IgYΔFc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD₅₀). Both immune sera, and egg-derived purified IgY/IgYΔFc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgYΔFc purified from normal geese (n=8), or no-treatment (n=8), developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral biological product capable of preventing a lethal disease when administered post-exposure.</p></div

ANDV DNA vaccine is immunogenic in geese.

<p><b>A</b>. Eight geese were vaccinated i.m. with 1mg ANDV DNA vaccine pWRG/AND-M(opt) or pWRG/AND-M(1.1) at 2 week intervals (blue arrows) using the PharmaJet V1. One year later the same, geese were booster vaccinated again with 1mg ANDV DNA pWRG/AND-M(opt) or pWRG/AND-M(opt2). Sera was collected from the vaccinated geese during the times indicated by red arrows. Egg collection is indicated by yellow ovals. <b>B.</b> Goose serum titers following initial vaccination series and <b>C.</b> long-range boost by PsVNA. Black lines indicate geese boosted with pWRG/AND-M(opt) and red lines indicate hamsters boosted with pWRG/AND-M(opt2). <b>D.</b> Mean of geese vaccinated initially with pWRG/AND-M and boosted with pWRG/AND-M(opt) (Group A) and pWRG/AND-M(opt2) (Group B).</p

Identification of ANDV glycoprotein G_n and G_c epitopes.

<p>Microarray slides were incubated with IgY, IgYΔFc, or IgY/IgYΔFc isolated for egg yolks of vaccinated either after the initial or booster vaccination series, or serum from vaccinated rabbits (first column- amino acid peptide starts with, second column- IgY from egg yolks after initial vaccination series, third column- IgYΔFc from egg yolks after initial vaccination series, fourth column- IgY/IgYΔFc from egg yolks after initial vaccination series, fifth column- IgY/IgYΔFc from egg yolks after booster vaccination, sixth column- sera from vaccinated rabbit). Reactivity was measured based on a spectrum ranging from no activity in white, mild reactivity in gray, to strong reactivity in red. Epitopes regions marked with a (*) indicate epitopes of high interest after long-range booster vaccination. (::) indicate previously published amino acid regions with which human sera from HPS patients were strongly reactive [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003803#pntd.0003803.ref034" target="_blank">34</a>]. (♦) indicate unique epitopes that rabbit IgG recognized strongly compared to IgY/IgYΔFc from eggs of vaccinated geese.</p

IgY/IgYΔFc from eggs collected from vaccinated geese has high-titer neutralizing activity.

<p><b>A.</b> Total IgY was purified from eggs collected after the initial vaccination series and long-range boost and evaluated for α-ANDV neutralizing activity by PsVNA. The red box indicates samples that were pooled for future animal experiments. <b>B.</b> Purified IgY was visualized by Coomassie stain.</p