Enhanced immune responses following heterologous vaccination with self-amplifying RNA and mRNA COVID-19 vaccines.

The optimal vaccination strategy to boost responses in the context of pre-existing immune memory to the SARS-CoV-2 spike (S) glycoprotein is an important question for global public health. To address this, we explored the SARS-CoV-2-specific humoral and cellular immune responses to a novel self-amplifying RNA (saRNA) vaccine followed by a UK authorised mRNA vaccine (BNT162b2) in individuals with and without previous COVID-19, and compared these responses with those who received an authorised vaccine alone. 35 subjects receiving saRNA (saRNA group) as part of the COVAC1 clinical trial and an additional 40 participants receiving an authorised SARS-CoV-2 vaccine only (non-saRNA group) were recruited. Antibody responses were measured by ELISA and a pseudoneutralisation assay for wildtype, Delta and Omicron variants. Cellular responses were measured by IFN-Æ´ ELISpot and an activation induced marker (AIM) assay. Approximately 50% in each group had previous COVID-19 prior to vaccination, confirmed by PCR or antibody positivity on ELISA. All of those who received saRNA subsequently received a full course of an authorised vaccine. The majority (83%) of those receiving saRNA who were COVID-19 naïve at baseline seroconverted following the second dose, and those with previous COVID-19 had an increase in antibody titres two weeks following saRNA vaccination (median 27-fold), however titres were lower when compared to mRNA vaccination. Two weeks following the 2nd authorised mRNA vaccine dose, binding and neutralising antibody titres were significantly higher in the saRNA participants with previous COVID-19, compared to non-saRNA, or COVID-19 naive saRNA participants. Cellular responses were again highest in this group, with a higher proportion of spike specific CD8+ than CD4+ T cells when compared to those receiving the mRNA vaccine only. These findings suggest an immunological benefit of increased antigen exposure, both from natural infection and vaccination, particularly evident in those receiving heterologous vaccination with saRNA and mRNA.

Using crowdsourcing at an academic conference to develop STI testing messaging for public dissemination.

OBJECTIVES: We provide a guide to conducting a crowdsourcing activity at an international sexually transmitted infection (STI) conference to design public messaging about STI testing and disseminating that messaging via social media. METHODS: A speaker gave a presentation at a conference plenary session on the concepts of cocreation, crowdsourcing and designathons, and the application of these participatory approaches in public health research. To illustrate one of these approaches (crowdsourcing), attendees in the audience were asked to take part in a voluntary participatory activity, in which they would pair up with a fellow attendee sitting nearby and write down an idea on a blank notecard. Dyads were given 10 min to create an entry responding to the prompt, 'Write something that inspires gonorrhoea and/or chlamydia testing (eg, picture, jingle, rhyme)'. Each entry was judged by at least four independent judges on a scale of 0 (lowest quality) to 10 (highest quality) based on their innovation and potential to promote chlamydia/gonorrhoea testing. Scores were averaged to determine the finalist entries. RESULTS: We received 32 entries. The average score was 6.41 and scores ranged from 4.5 to 8 (median 6.63, IQR 5.75, 7.06). Half of entries (n=16) were slogans, 15.6% (n=5) were poems/rhymes, 12.5% (n=4) were memes/images, 9.4% (n=3) were programme implementation ideas, 3.1% (n=1) was a song verse, and 3.1% (n=1) was a video idea. One finalist entry was a meme and received 720 impressions, 120 engagements, 27 detail expands, 19 likes, 6 reposts and 1 response on Twitter. The second finalist entry was a slogan and received 242 impressions, 16 engagements, 6 detail expands, 4 likes and 2 reposts. CONCLUSIONS: Conducting crowdsourcing activities at future conferences may be an innovative, feasible way to develop and disseminate engaging and important STI and other health messaging to the public in a short period of time.

The HI V O pen Call on I nformed C onsent and E thics in Research (VOICE) for Adolescents and Young Adults: A Digital Crowdsourcing Open Call in Low- and Middle-Income Countries.

BACKGROUND: Many adolescents and young adults (AYAs; 10-24 years old) are excluded from HIV research because of social, ethical, and legal challenges with informed consent, resulting in limited AYA-focused data. We use a participatory approach to identify strategies for improving AYA consent processes in HIV research in low- and middle-income countries (LMICs). METHODS: We conducted a digital crowdsourcing open call for ideas to improve AYA consent to HIV research in LMICs. Crowdsourcing involves engaging a group of people in problem-solving, then sharing emergent solutions. Submissions were evaluated by 3 independent judges using predefined criteria, with exceptional strategies receiving prizes. Demographic data were collected, and textual data were qualitatively analyzed for emergent themes in barriers and facilitators for improving AYA consent in HIV research, guided by a socioecological model. RESULTS: We received 110 strategies total; 65 were eligible for evaluation, 25 of which were identified as finalists. Fifty-eight participants from 10 LMICs submitted the 65 eligible submissions, of which 30 (52%) were 18 to 24 years old. Thematic analysis identified 10 barriers to AYA consent, including HIV stigma, limited education, and legal/regulatory barriers. Strategies for improving AYA consent processes revealed 7 potential facilitators: enhancing AYA engagement in research, involving parents/guardians, improving education/awareness, improving institutional practices/policy, making research participation more AYA-friendly, enhancing engagement of other key communities of interest, and empowering AYA. CONCLUSIONS: Diverse communities of interest in LMICs developed compelling strategies to enhance informed consent that may improve AYA inclusion in HIV research. These data will be used to develop practical guidance on improving AYA consent processes.

Awareness of, willingness to use, and experiences with Pre-exposure prophylaxis among youth in Nigeria.

BACKGROUND: Youth (ages 14-24) in Nigeria have disproportionately high rates of new HIV infection. Pre-exposure prophylaxis could substantially reduce new infections among youth but has not been scaled up. This cross-sectional study aimed to assess Pre-exposure prophylaxis awareness, willingness to use, and prior use of Pre-exposure prophylaxis among youth in Nigeria. METHODS: This is a secondary analysis of cross-sectional data from a quasi-experimental pilot study (clinical trial NCT04070287). The analysis focused on Pre-exposure prophylaxis awareness, willingness to use, and prior use among 324 youth recruited between September 2019 to March 2020. Descriptive statistics were calculated as frequencies and percentages for categorical variables and means and standard deviations for continuous variables. RESULTS: Of the 324 participants, the mean age and standard deviation were 21.17 (± 2.20) years. The majority were 20-24 years old (75.9%) and male (57.7%). Only 30.7% used condoms consistently over three months. Regarding Pre-exposure prophylaxis awareness and willingness, 62.6% had never heard of Pre-exposure prophylaxis, and 158 (50.1%) reported willingness to use Pre-exposure prophylaxis. Only 10 (3.2%) reported having used Pre-exposure prophylaxis. CONCLUSION: Nigerian youth have low awareness of and prior use of Pre-exposure prophylaxis. Given the gap between prior use and willingness to use Pre-exposure prophylaxis, our findings suggest missed opportunities to prevent new HIV infections among youth in Nigeria. Efforts to increase awareness and uptake of Pre-exposure prophylaxis among this population should consider youth-led Pre-exposure prophylaxis outreach efforts and effectively communicate the benefits of Pre-exposure prophylaxis to this population. TRIAL REGISTRATION: NCT04070287, the Date of registration of the trial is 20-07-2019.

Sustaining sexual health programs: practical considerations and lessons from the President's Emergency Plan for AIDS Relief.

Enhancing the sustainability of sexual health programs is important, but there are few practical tools to facilitate this process. Drawing on a sustainability conceptual framework, this Editorial proposes four ideas to increase the sustainability of sexual health programs - early planning, equitable community engagement, return on investment, and partnerships to address social determinants. Early planning during the design of a sexual health program is important for sustainability because it provides an opportunity for the team to build factors relevant to sustainability into the program itself. Equitable community engagement can expand multi-sectoral partnerships for institutionalisation, identify allies for implementation, and strengthen relationships between beneficiaries and researchers. From a financial perspective, considering the return on investment could increase the likelihood of sustainability. Finally, partnerships to address social determinants can help to identify organisations with a similar vision. Existing sustainability frameworks can be used to measure each of these key elements. Several approaches can be used to enhance the sustainability of sexual health programs. The President's Emergency Plan for AIDS Relief provides potential lessons for increasing the sustainability of sexual health programs in diverse global settings.

Sexual behaviours and sexual health among middle-aged and older adults in Britain.

OBJECTIVES: Population-representative studies of the sexual health of middle-aged and older adults are lacking in ageing societies. This study aimed to identify latent patterns of sexual behaviours and health of people aged 45-74 years. METHODS: We conducted a latent class analysis of the National Attitudes and Sexual Lifestyles Survey (Natsal-3), a nationally representative survey conducted in Britain in 2011. RESULTS: Of the 5260 respondents aged 45-74 years, 48.86% of men and 44.91% of women belonged to the Content Caseys class who reported good sexual health. The Infrequent Indigos (30.94% of men, 44.38% of women) were characterised by a lack of sexual activity, reported some dissatisfaction, and were more likely to have a disability. The Low-Functioning Lees (11.65% of men, 8.41% of women) reported some more disability and had issues with sexual functioning and higher levels of distress. The Multiple-Partnered Morgans (8.62% of men, 2.30% of women) were characterised by a greater number of sexual partners and several risk behaviours. CONCLUSIONS: The use of these four classes can aid in improved targeting of tailored sexual health services to improve sexual function, sexual satisfaction, reduce distress and risky behaviours among middle-aged and older adults. These services should be inclusive of the disabled community.

"Just felt so convenient and warm by the non-profit help". Optimizing HIV self-test secondary distribution among men who have sex with men in China.

ABSTRACTSecondary distribution of HIV self-test is promising to increase testing uptake while the facilitators and barriers of secondary distribution remain unclear. In-depth interviews were conducted with 22 MSM who had participated in secondary distribution of HIVST in southern China. Data were thematically analyzed to capture participants' motivations, procedures, and challenges when accessing and distributing self-tests. MSM in China are willing to distribute HIVST to members in their social network, but their decision-making is impacted by their ability to broach sexual health conversations, evaluations of the recipients, and perceived trustworthiness of the self-test. Our study suggested that several strategies, including creating a friendly environment for sexual health conversations and establishing nationwide policies related to quality assured self-tests and standardized self-testing protocols, may be helpful to advance this approach in China.

Increasing Men's Engagement in HIV Testing and Treatment Programs Through Crowdsourcing: A Mixed-Methods Analysis in Eswatini.

BACKGROUND: Sub-Saharan African HIV programs have had limited success in engaging men. Crowdsourcing contests may be a useful method to spur men's engagement in HIV services. We evaluated contributions and social media response to a crowdsourcing contest focused on increasing men's engagement in Eswatini HIV services. METHODS: We conducted a crowdsourcing contest to gain insight from the public on how HIV campaigns can more effectively engage young (20-40 years old) men in HIV services. Eligible submissions included images, songs, videos, and Internet memes. We used standard qualitative methods to examine textual themes from submissions. We examined social media response using Facebook analytics, comparing the number of people reached through crowdsourced HIV messages and the number of people reached through conventional HIV messages. RESULTS: We received 144 submissions from 83 participants. They represented 55 towns and all 4 regions of Eswatini. The contest page gained 461 followers on Facebook. Emergent themes included appealing to men's roles as protectors by suggesting that they need to take care of their own health to continue safeguarding their families. Crowdsourced messages reached a mean of 88 individuals across 4 posts; conventional messages reached a mean of 75 individuals across 4 posts. CONCLUSIONS: Crowdsourcing contest submissions provided insight on how to encourage men to engage in Eswatini HIV services. Crowdsourcing contests can be effective in collecting messages from men to create more locally relevant communication materials for HIV programs.

Broadening community engagement in clinical research: Designing and assessing a pilot crowdsourcing project to obtain community feedback on an HIV clinical trial.

BACKGROUND/AIMS: Community engagement is widely acknowledged as an important step in clinical trials. One underexplored method for engagement in clinical trials is crowdsourcing. Crowdsourcing involves having community members attempt to solve a problem and then publicly sharing innovative solutions. We designed and conducted a pilot using a crowdsourcing approach to obtain community feedback on an HIV clinical trial, called the Acceptability of Combined Community Engagement Strategies Study. In this work, we describe and assess the Acceptability of Combined Community Engagement Strategies Study's crowdsourcing activities in order to examine the opportunities of crowdsourcing as a clinical trial community engagement strategy. METHODS: The crowdsourcing engagement activities involved in the Acceptability of Combined Community Engagement Strategies Study were conducted in the context of a phase 1 HIV antibody trial (ClinicalTrials.gov identifier: NCT03803605). We designed a series of crowdsourcing activities to collect feedback on three aspects of this clinical trial: the informed consent process, the experience of participating in the trial, and fairness/reciprocity in HIV clinical trials. All crowdsourcing activities were open to members of the general public 18 years of age or older, and participation was solicited from the local community. A group discussion was held with representatives of the clinical trial team to obtain feedback on the utility of crowdsourcing as a community engagement strategy for informing future clinical trials. RESULTS: Crowdsourcing activities made use of innovative tools and a combination of in-person and online participation opportunities to engage community members in the clinical trial feedback process. Community feedback on informed consent was collected by transforming the clinical trial's informed consent form into a series of interactive video modules, which were screened at an open public discussion. Feedback on the experience of trial participation involved designing three fictional vignettes which were then transformed into animated videos and screened at an open public discussion. Finally, feedback on fairness/reciprocity in HIV clinical trials was collected using a crowdsourcing idea contest with online and in-person submission opportunities. Our public discussion events were attended by 38 participants in total; our idea contest received 43 submissions (27 in-person, 16 online). Facebook and Twitter metrics demonstrated substantial engagement in the project. The clinical team found crowdsourcing primarily useful for enhancing informed consent and trial recruitment. CONCLUSION: There is sufficient lay community interest in open calls for feedback on the design and conduct of clinical trials, making crowdsourcing both a novel and feasible engagement strategy. Clinical trial researchers are encouraged to consider the opportunities of implementing crowdsourcing to inform trial processes from a community perspective.

Crowdsourcing contests to facilitate community engagement in HIV cure research: a qualitative evaluation of facilitators and barriers of participation.

BACKGROUND: As HIV cure research advances, there is an increasing need for community engagement in health research, especially in low- and middle-income countries with ongoing clinical trials. Crowdsourcing contests provide an innovative bottom-up way to solicit community feedback on clinical trials in order to enhance community engagement. The objective of this study was to identify facilitators and barriers to participating in crowdsourcing contests about HIV cure research in a city with ongoing HIV cure clinical trials. METHODS: We conducted in-depth interviews to evaluate facilitators and barriers to participating in crowdsourcing contests in Guangzhou, China. Contests included the following activities: organizing a call for entries, promoting the call, evaluating entries, celebrating exceptional entries, and sharing entries. We interviewed 31 individuals, including nine HIV cure clinical trial participants, 17 contest participants, and five contest organizers. Our sample included men who have sex with men (20), people living with HIV (14), and people who inject drugs (5). We audio-recorded, transcribed, and thematically analyzed the data using inductive and deductive coding techniques. RESULTS: Facilitators of crowdsourcing contest participation included responsiveness to lived experiences, strong community interest in HIV research, and community trust in medical professionals and related groups. Contests had more participants if they responded to the lived experiences, challenges, and opportunities of living with HIV in China. Strong community interest in HIV research helped to drive the formulation and execution of HIV cure contests, building support and momentum for these activities. Finally, participant trust in medical professionals and related groups (community-based organizations and contest organizers) further strengthened the ties between community members and researchers. Barriers to participating in crowdsourcing contests included persistent HIV stigma and myths about HIV. Stigma associated with discussing HIV made promotion difficult in certain contexts (e.g., city squares and schools). Myths and misperceptions about HIV science confused participants. CONCLUSIONS: Our data identified facilitators and barriers of participation in HIV cure crowdsourcing contests in China. Our findings could complement existing HIV community engagement strategies and help to design HIV contests for community engagement in other settings, particularly in low- and middle-income countries.

Homoprejudiced violence among Chinese men who have sex with men: a cross-sectional analysis in Guangzhou, China.

BACKGROUND: Homoprejudiced violence, defined as physical, verbal, psychological and cyber aggression against others because of their actual or perceived sexual orientation, is an important public health issue. Most homoprejudiced violence research has been conducted in high-income countries. This study examined homoprejudiced violence among men who have sex with men (MSM) in Guangzhou, China. METHODS: MSM in a large Chinese city, Guangzhou, completed an online survey. Data about experiencing and initiating homoprejudiced violence was collected. Multivariable logistic regression analyses, controlling for age, residence, occupation, heterosexual marriage, education and income, were carried out to explore associated factors. RESULTS: A total of 777 responses were analyzed and most (64.9%) men were under the age of 30. Three-hundred-ninety-nine (51.4%) men experienced homoprejudiced violence and 205 (25.9%) men perpetrated homoprejudiced violence against others. Men who identified as heterosexual were less (AOR = 0.6, 95% CI: 0.4-0.9) likely to experience homoprejudiced violence compared to men who identified as gay. Men who experienced homoprejudiced violence were more likely to initiate homoprejudiced violence (AOR = 2.44, 95% CI: 1.6-3.5). Men who disclosed their sexual orientation to other people were more likely to experience homoprejudiced violence (AOR = 1.8, 95% CI:1.3-2.5). CONCLUSIONS: These findings suggest the importance of further research and the implementation of interventions focused on preventing and mitigating the effects of homoprejudiced violence among MSM in China.

Forming and implementing community advisory boards in low- and middle-income countries: a scoping review.

BACKGROUND: Community advisory boards (CABs) have expanded beyond high-income countries (HICs) and play an increasing role in low- and middle-income country (LMIC) research. Much research has examined CABs in HICs, but less is known about CABs in LMICs. The purposes of this scoping review are to examine the creation and implementation of CABs in LMICs, including identifying frequently reported challenges, and to discuss implications for research ethics. METHODS: We searched five databases (PubMed, Embase, Global Health, Scopus, and Google Scholar) for publications describing or evaluating CABs in LMICs. Two researchers independently reviewed articles for inclusion. Data related to the following aspects of CABs were extracted from included publications: time, country, financial support, research focus, responsibilities, and challenges. Thematic analyses were used to summarize textual data describing challenges. RESULTS: Our search yielded 2005 citations, 83 of which were deemed eligible for inclusion. Most studies (65) were published between 2010 and 2017. Upper-middle-income countries were more likely to have studies describing CABs, with South Africa (17), China (8), and Thailand (7) having the greatest numbers. The United States National Institutes of Health was the main source of financial support for CABs. Many CABs (53/88, 60%) focused on HIV research. Thirty-four studies reported how CABs influenced the informed consent process for clinical trials or other aspects of research ethics. CAB responsibilities were related to clinical trials, including reviewing study protocols, educating local communities about research activities, and promoting the ethical conduct of research. Challenges faced by CABs included the following: incomplete ethical regulations and guidance; limited knowledge of science among members of communities and CABs; unstable and unbalanced power relationships between researchers and local communities; poor CAB management, including lack of formal participation structures and absence of CAB leadership; competing demands for time that limited participation in CAB activities; and language barriers between research staff and community members. Several challenges reflected shortcomings within the research team. CONCLUSIONS: Our findings examine the formation and implementation of CABs in LMICs and identify several ethical challenges. These findings suggest the need for further ethics training among CAB members and researchers in LMICs.

An ED paradox: patients who arrive by ambulance and then leave without consulting an ED provider.

BACKGROUND: Scientists have called for strategies to identify ED patients with unmet needs. We identify the unique profile of ED patients who arrive by ambulance and subsequently leave without consulting a provider (ie, a paradoxical visit, PV). METHODS: Using a retrospective cohort design, administrative data from Winnipeg, Manitoba were interrogated to identify all ED patients 17+ years old as having zero, single or multiple PVs in 2012/2013. Analyses compare the sociodemographic, physical (eg, arthritis), mental (eg, substance abuse) and concurrent healthcare use profile of non-PV, single and multiple PV patients. RESULTS: The study cohort consisted of 122 639 patients with 250 754 ED visits. Across all ED sites, 2.3% of patients (N=2815) made 3387 PVs, comprising 1.4% of all ED visits. Descriptively, more single versus non-PV patients lived in urban core and lowest-income areas, were frequent ED users generally, were substance abusers and had seven plus primary care physician visits. Multiple PV patients had a similar but more extreme profile versus their single PV counterparts (eg, 54.7% of multiple vs 27.4% of single PV patients had substance abuse challenges). From multivariate statistics, single versus non-PV patients are defined uniquely by their frequent ED use, by their substance abuse, as living in a core and low income area, and as having multiple visits with primary care physicians. CONCLUSIONS: PV patients have needs that do not align with the acute model of ED care. These patients may benefit from a more integrated care approach likely involving allied health professionals.

Pressure Ulcers Among Newly Admitted Nursing Home Residents: Measuring the Impact of Transferring From Hospital.

OBJECTIVES: Pressure ulcers (PUs) are reported more often among newly admitted nursing home (NH) residents who transfer from hospital versus community. We examine for whom this increased risk is greatest, further defining hospitalized patients most in need of better PU preventive care. RESEARCH DESIGN: Retrospective observational cohort study. SUBJECTS: All NH residents (N=5617) newly admitted between April 1, 2008 and March 31, 2012 in Winnipeg, MB, Canada. MEASURES: RAI-MDS 2.0 data were linked to administrative health care use files capturing each person's NH admission date, their presence of a PU at this time, whether they transferred into NH from hospital or community, and their PU susceptibility (eg, amount of help needed to maneuver in bed or to transfer from one surface to another, frequency of incontinence, presence of diabetes, amount of food consistently left uneaten). Log-binomial regression with interaction terms was used to analyze data. RESULTS: 67.6% of our cohort transferred into a NH directly from hospital; 9.2% of these residents were reported to have a stage 1+ PU on NH admission versus 2.6% of those who transferred from community. From regression models, transferring from hospital versus community was associated with increased PU risk equally across various subgroups of less and more susceptible residents. CONCLUSIONS: Transferring from hospital versus community places both more and less susceptible newly admitted NH residents at increased PU risk. Using evidence-based preventive care practices is thus needed for all subgroups of hospital patients before NH use, to help reduce PU risk.

Integrating and evaluating sex and gender in health research.

Both sex (biological factors) and gender (socio-cultural factors) shape health. To produce the best possible health research evidence, it is essential to integrate sex and gender considerations throughout the research process. Despite growing recognition of the importance of these factors, progress towards sex and gender integration as standard practice has been both slow and uneven in health research. In this commentary, we examine the challenges of integrating sex and gender from the research perspective, as well as strategies that can be used by researchers, funders and journal editors to address these challenges. Barriers to the integration of sex and gender in health research include problems with inconsistent terminology, difficulties in applying the concepts of sex and gender, failure to recognise the impact of sex and gender, and challenges with data collection and datasets. We analyse these barriers as strategic points of intervention for improving the integration of sex and gender at all stages of the research process. To assess the relative success of these strategies in any given study, researchers, funders and journal editors would benefit from a tool to evaluate the quality of sex and gender integration in order to establish benchmarks in research excellence. These assessment tools are needed now amidst growing institutional recognition that both sex and gender are necessary elements for advancing the quality and utility of health research evidence.

Implementing a domestic violence screening program.

The purpose of this study was to design and implement a domestic violence (DV) screening protocol. Trauma patients meeting inclusion criteria (hospitalized > 48 hours) were given a four question DV screen. If abuse was found, a comprehensive DV questionnaire followed. Barriers to screening and results were recorded. Compliance during the pilot test showed 23 of 157 (14.6%) admitted patients were screened. In the implementation year, 446 of 721 (61.9%) were screened. During the 10-month follow-up, 499 of 619 (80.6%) patients were screened. Lack of social work resources was the primary barrier to screening, but compliance increased and was maintained after the study period.

The role of helper lipids in optimising nanoparticle formulations of self-amplifying RNA.

Lipid nanoparticle (LNP) formulation plays a vital role in RNA vaccine delivery. However, further optimisation of self-amplifying RNA (saRNA) vaccine formulation could help enhance seroconversion rates in humans and improve storage stability. Altering either the ionisable or helper lipid can alter the characteristics and performance of formulated saRNA through the interplay of the phospholipid's packing parameter and the geometrical shape within the LNP membrane. In this study, we compared the impact of three helper lipids (DSPC, DOPC, or DOPE) used with two different ionisable lipids (MC3 and C12-200) on stability, transfection efficiency and the inflammation and immunogenicity of saRNA. While helper lipid identity altered saRNA expression across four cell lines in vitro, this was not predictive of an ex vivo or in vivo response. The helper lipid used influenced LNP storage where DSPC provided the best stability profile over four weeks at 2-8 °C. Importantly, helper lipid impact on LNP storage stability was the best predictor of expression in human skin explants, where C12-200 in combination with DSPC provided the most durable expression. C12-200 LNPs also improved protein expression (firefly luciferase) and humoral responses to a SARS-CoV-2 spike saRNA vaccine compared to MC3 LNPs, where the effect of helper lipids was less apparent. Nevertheless, the performance of C12-200 in combination with DSPC appears optimal for saRNA when balancing preferred storage stability requirements against in vivo and ex vivo potency. These data suggest that helper lipid influences the stability and functionality of ionisable lipid nanoparticle-formulated saRNA.

An investigation of trachoma vaccine regimens by the chlamydia vaccine CTH522 administered with cationic liposomes in healthy adults (CHLM-02): a phase 1, double-blind trial.

BACKGROUND: There is no vaccine against the major global pathogen Chlamydia trachomatis; its different serovars cause trachoma in the eye or chlamydia in the genital tract. We did a clinical trial administering CTH522, a recombinant version of the C trachomatis major outer membrane molecule, in different dose concentrations with and without adjuvant, to establish its safety and immunogenicity when administered intramuscularly, intradermally, and topically into the eye, in prime-boost regimens. METHODS: CHLM-02 was a phase 1, double-blind, randomised, placebo-controlled trial at the National Institute for Health Research Imperial Clinical Research Facility, London, UK. Participants were healthy men and non-pregnant women aged 18-45 years, without pre-existing C trachomatis genital infection. Participants were assigned into six groups by the electronic database in a pre-prepared randomisation list (A-F). Participants were randomly assigned (1:1:1:1:1) to each of the groups A-E (12 participants each) and 6 were randomly assigned to group F. Investigators were masked to treatment allocation. Groups A-E received investigational medicinal product and group F received placebo only. Two liposomal adjuvants were compared, CAF01 and CAF09b. The groups were intramuscular 85 µg CTH522-CAF01, or placebo on day 0 and two boosters or placebo at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (A); intramuscular 85 µg CTH522-CAF01, two boosters at day 28 and 112 with additional topical ocular administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (B); intramuscular 85 µg CTH522-CAF01, two boosters at day 28 and 112 with additional intradermal administration of CTH522, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (C); intramuscular 15 µg CTH522-CAF01, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (D); intramuscular 85 µg CTH522-CAF09b, two boosters at day 28 and 112, and a mucosal recall with either placebo or CTH522 topical ocularly at day 140 (E); intramuscular placebo (F). The primary outcome was safety; the secondary outcome (humoral immunogenicity) was the percentage of trial participants achieving anti-CTH522 IgG seroconversion, defined as four-fold and ten-fold increase over baseline concentrations. Analyses were done as intention to treat and as per protocol. The trial is registered with ClinicalTrials.gov, NCT03926728, and is complete. FINDINGS: Between Feb 17, 2020 and Feb 22, 2022, of 154 participants screened, 65 were randomly assigned, and 60 completed the trial (34 [52%] of 65 women, 46 [71%] of 65 White, mean age 26·8 years). No serious adverse events occurred but one participant in group A2 discontinued dosing after having self-limiting adverse events after both placebo and investigational medicinal product doses. Study procedures were otherwise well tolerated; the majority of adverse events were mild to moderate, with only seven (1%) of 865 reported as grade 3 (severe). There was 100% four-fold seroconversion rate by day 42 in the active groups (A-E) and no seroconversion in the placebo group. Serum IgG anti-CTH522 titres were higher after 85 µg CTH522-CAF01 than 15 µg, although not significantly (intention-to-treat median IgG titre ratio groups A-C:D=5·6; p=0·062), with no difference after three injections of 85 µg CTH522-CAF01 compared with CTH522-CAF09b (group E). Intradermal CTH522 (group C) induced high titres of serum IgG anti-CTH522 neutralising antibodies against serovars B (trachoma) and D (urogenital). Topical ocular CTH522 (group B) at day 28 and 112 induced higher total ocular IgA compared with baseline (p<0·001). Participants in all active vaccine groups, particularly groups B and E, developed cell mediated immune responses against CTH522. INTERPRETATION: CTH522, adjuvanted with CAF01 or CAF09b, is safe and immunogenic, with 85 µg CTH522-CAF01 inducing robust serum IgG binding titres. Intradermal vaccination conferred systemic IgG neutralisation breadth, and topical ocular administration increased ocular IgA formation. These findings indicate CTH522 vaccine regimens against ocular trachoma and urogenital chlamydia for testing in phase 2, clinical trials. FUNDING: The EU Horizon Program TRACVAC.

Data science research in sub-Saharan Africa: Ethical considerations in crowdsourcing for community engagement.

The growth in data science research in sub-Saharan Africa raises important ethical questions for the collection and use of 'big data' in this context, with particularly disparate implications for the most vulnerable and marginalised populations. While enhanced public involvement may be able to mitigate some of these risks, data science presents some unique barriers to community engagement efforts, including limited data literacy, lack of transparency in data collection and use, and little opportunity to 'opt out' from participation. The participatory approach of crowdsourcing offers a promising solution to address the critical need for community engagement. Crowdsourcing involves inviting a group to contribute solutions to a problem, and then publicly sharing the results for implementation. By crowdsourcing stakeholder ideas for innovative ways to enhance public involvement in data science research, the Research for Ethical Data Science in Southern Africa (REDSSA) project is leading the efforts to close the community engagement gap. Promising strategies that emerge from these efforts will ultimately help to shape more ethical and equitable data science research in Africa as this field continues to grow.

Crowdsourcing to support training for public health: A scoping review.

Crowdsourcing is an interactive process that has a group of individuals attempt to solve all or part of a problem and then share solutions with the public. Crowdsourcing is increasingly used to enhance training through developing learning materials and promoting mentorship. This scoping review aims to assess the literature on crowdsourcing for training in public health. We searched five medical and public health research databases using terms related to crowdsourcing and training. For this review, the concept of crowdsourcing included open calls, designathons, and other activities. We used a PRISMA checklist for scoping reviews. Each full-text was assessed by two independent reviewers. We identified 4,071 citations, and 74 studies were included in the scoping review. This included one study in a low-income country, 15 studies in middle-income countries, 35 studies in high-income countries, and 11 studies conducted in multiple countries of varying income levels (the country income level for 12 studies could not be ascertained). Nine studies used open calls, 35 used a hackathon, designathon or other "a-thon" event, and 30 used other crowdsourcing methods, such as citizen science programs and online creation platforms. In terms of crowdsourcing purpose, studies used crowdsourcing to educate participants (20 studies), develop learning materials (17 studies), enhance mentorship (13 studies) and identify trainees (9 studies). Fifteen studies used crowdsourcing for more than one training purpose. Thirty-four studies were done in-person, 31 were conducted virtually and nine used both meeting options for their crowdsourcing events. Seventeen studies generated open access materials. Our review found that crowdsourcing has been increasingly used to support public health training. This participatory approach can be a useful tool for training in a variety of settings and populations. Future research should investigate the impact of crowdsourcing on training outcomes.