Vaccine Clinical Trials Research Articles

IL-2/anti-IL-2 antibody complexes augment immune responses to therapeutic cancer vaccines

One driver of the high failure rates of clinical trials for therapeutic cancer vaccines is likely the inability to sufficiently engage conventional dendritic cells (cDCs), the antigen-presenting cell (APC) subset that is specialized in priming antitumor T cells. Here, we demonstrate that, relative to vaccination with an injectable mesoporous silica rod (MPS) vaccine alone (Vax), combining MPS vaccines with CD122-biased IL-2/anti-IL-2 antibody complexes (IL-2cx) drives ~3-fold expansion of cDCs at the vaccination sites, vaccine-draining lymph nodes, and spleens of treated mice. Furthermore, relative to Vax alone, Vax+IL-2cx led to a ~3-fold increase in the numbers of CD8 + T cells and ~15-fold increase in the numbers of NK cells at the vaccination site. Notably, with both the model protein antigen OVA as well as various peptide neoantigens, Vax+IL-2cx induced ~5 to 30-fold greater numbers of circulating antigen-specific CD8 + T cells relative to Vax alone. We further demonstrate that Vax+IL-2cx leads to significantly improved efficacy in the MC38 colon carcinoma model relative to either monotherapy alone, driving complete regressions in 50% of mice in a cDC-dependent manner. Relative to vaccine alone, Vax+IL-2cx led to comparable numbers of CD8 + T cells, but markedly greater numbers of NK cells and activated cDCs in the B16F10 melanoma tumor microenvironment post-therapy. Taken together, these findings suggest that the administration of factors that engage both the cDC-CD8 + T cell and cDC-NK cell axes can boost the potency of therapeutic cancer vaccines.

GeM-LR: Discovering predictive biomarkers for small datasets in vaccine studies.

Despite significant progress in vaccine research, the level of protection provided by vaccination can vary significantly across individuals. As a result, understanding immunologic variation across individuals in response to vaccination is important for developing next-generation efficacious vaccines. Accurate outcome prediction and identification of predictive biomarkers would represent a significant step towards this goal. Moreover, in early phase vaccine clinical trials, small datasets are prevalent, raising the need and challenge of building a robust and explainable prediction model that can reveal heterogeneity in small datasets. We propose a new model named Generative Mixture of Logistic Regression (GeM-LR), which combines characteristics of both a generative and a discriminative model. In addition, we propose a set of model selection strategies to enhance the robustness and interpretability of the model. GeM-LR extends a linear classifier to a non-linear classifier without losing interpretability and empowers the notion of predictive clustering for characterizing data heterogeneity in connection with the outcome variable. We demonstrate the strengths and utility of GeM-LR by applying it to data from several studies. GeM-LR achieves better prediction results than other popular methods while providing interpretations at different levels.

Improving precision of vaccine efficacy evaluation using immune correlate data in time-to-event models.

Understanding potential differences in vaccine-induced protection between demographic subgroups is key for vaccine development. Vaccine efficacy evaluation across these subgroups in phase 2b or 3 clinical trials presents challenges due to lack of precision: such trials are typically designed to demonstrate overall efficacy rather than to differentiate its value between subgroups. This study proposes a method for estimating vaccine efficacy using immunogenicity (instead of vaccination status) as a predictor in time-to-event models. The method is applied to two datasets from immunogenicity sub-studies of vaccine phase 3 clinical trials for zoster and dengue vaccines. Results show that using immunogenicity-based estimation of efficacy in subgroups using time-to-event models is more precise than the standard estimation. Incorporating immune correlate data in time-to-event models improves precision in estimating efficacy (i.e., yields narrower confidence intervals), which can assist vaccine developers and public health authorities in making informed decisions.

“Let’s say it wears an Ebola Coat, but it’s not Ebola”: The Rhetoric and Politics of Reframing a Vaccine for a Transnational Clinical Trial

Focusing on how disease, health and vaccine research take on different forms, meanings and interpretations in diverse contexts, we examine the use of rhetoric to recruit people living with HIV in sub-Saharan Africa for an Ebola vaccine clinical trial. Conducted after the West African Ebola outbreak in a country that had not been affected by Ebola, the urgency, relevance and materiality of disease, health and biomedical research takes on different shapes, meanings and understandings. The limitations of multilateral initiatives to address inequalities in associated healthcare and access to essential medicines and vaccines highlight the tensions created when neither local researchers nor patient communities have been involved in the design or planning of the trial, and when the pathologies targeted by experimental technologies are either inappropriate for the people they are aimed at, or unfold without the knowledge of a social consensus. By deciphering the metaphorical discourse on an Ebola vaccine candidate and the erasure of a viral ontology from the hybrid technology to which it gives rise, we understand that the discourse of clinic staff makes it possible to establish a scientific truth in the service of instrumental productivity: manufacturing consent and recruiting arms for vaccine shots. In this article, we show that the closure of biomedicine to an esoteric discourse reflects the weakness of science in communicating what it actually does and the techniques it produces. It also addresses the failure of community engagement in the field of emerging infectious diseases.

Enterovirus Antibodies: Friends and Foes.

Enteroviruses (EV) initiate replication by binding to their cellular receptors, leading to the uncoating and release of the viral genome into the cytosol of the host cell. Neutralising antibodies (NAbs) binding to epitopes on enteroviral capsid proteins can inhibit this infectious process through several mechanisms of neutralisation in vitro. Fc-mediated antibody effector functions such as antibody-dependent cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis have also been described for some EV. However, antibody binding to virions does not always result in viral neutralisation. Non-neutralising antibodies, or sub-neutralising concentrations of antibodies, can enhance infection of viruses, leading to more severe pathologies. This phenomenon, known as antibody-dependent enhancement (ADE) of infection, has been described in vitro and/or in vivo for EV including poliovirus, coxsackievirus B and EV-A71. It has been shown that ADE of EV infection is mediated by FcγRs expressed by monocytes, macrophages, B lymphocytes and granulocytes. Antibodies play a crucial role in the diagnosis and monitoring of infections. They are valuable markers that have been used to establish a link between enteroviral infection and chronic diseases such as type 1 diabetes. Monoclonal and polyclonal antibodies targeting enteroviral proteins have been developed and shown to be effective to prevent or combat EV infections in vitro and in vivo. In addition, vaccines are under development, and clinical trials of vaccines are underway or have been completed, providing hope for the prevention of diseases due to EV. However, the ADE of the infection should be considered in the development of anti-EV antibodies or safe vaccines.

Epidemiology, Pathogenesis, and Vaccine Development of Acne

Acne is a widespread and chronic inflammatory disease of the pilosebaceous glands affecting millions of people worldwide, particularly among adolescents. The current treatment method is mainly oral and smear medication, combined with a variety of physical and chemical therapy used as adjuvant therapy, alternative therapy or sequelae treatment. However, due to antibiotic resistance and bacteria evolve over time, need a vaccine as a new alternative treatment, in recent years, with the rapid development of molecular biology and immunology, based on specific antigen antibody technology acne vaccine has made significant progress, but there is still no successful development of acne vaccine. This paper analyzes the main four pathogenesis of acne and the current treatment, including oral and daub anti-inflammatory drugs and antibacterial drugs, supplemented by physical and chemical therapy, focus on the development of acne vaccine, present situation, challenges and future trend, hope to further promote the research and development of acne vaccine provide certain theoretical basis and reference value, and provide new ideas and methods for the prevention and treatment of acne. And acne pathogenesis complex and cannot determine the vaccine clinical trial effect these two problems are not solved, pathogenic mechanism involves multiple complex factors, a single vaccine may not have enough protective effect, difficult to completely prevent or cure acne, therefore, the next step need to consider targeting multiple pathogens and virulence factors combination of multivalent vaccine, and need for long-term clinical trials and observation.

The TB vaccine clinical trial centre directory: An inventory of clinical trial centres in Sub-Saharan Africa.

There are over ten vaccine candidates for tuberculosis (TB) in the clinical pipeline that require testing in TB-prevalent populations. To accelerate the clinical development of TB vaccines, a directory of clinical trial centres was established in sub-Saharan Africa (SSA) to assess capacity for conducting late-stage TB vaccine trials. TB vaccine-related parameters were identified, and trial centres in SSA were identified and prioritized based on whether they had experience with TB or non-TB vaccine trials. A survey was sent to identified centres, and the resulting directory presents their capacity for TB vaccine trials. Centres that identified as eligible for TB vaccine trials also had the opportunity to participate to the survey. This article provides an overview of the TB vaccine clinical trial centre directory, including the number and distribution of centres, their general characteristics, and their experience with prior TB vaccine trials. It includes information on the capacity of the centres, such as laboratory biosafety level, patient support, and community engagement. It also includes a case study to demonstrate how the directory can be used to identify trial centres with specific capabilities needed for a particular TB vaccine trial. Of the 134 identified centres, 56 provided information. Of these centres, 51 (91%) had phase 3 clinical trial experience and previous TB trials were conducted at 38 centres. Regarding TB vaccine trials, 19 centres conducted prevention of disease trials, 14 conducted prevention of infection trials, and 27 had no experience with TB vaccine clinical trials. From the respondents, 29 centers in South Africa were identified that could potentially conduct TB vaccine trials, followed by Tanzania (5), Kenya (5), Nigeria (3), and Uganda and Ethiopia (2 each). Trial sites in other countries were underrepresented, based on this survey. The establishment of a clinical trial centre directory can provide a basis for decision-making by various stakeholders. Despite some limitations in survey methodology, the findings suggest opportunities for expanding the evaluation of clinical trial capacity in other disease-prevalent countries and continents. Such data would be valuable in further enriching the Clinical Trial Community which a resource that geographically highlights clinical trial investments and capacities in African research ecosystem. New TB vaccine candidates need to be assessed in clinical trials in countries with high rates of TB in the coming years.An open-access directory of TB vaccine clinical trial centres in sub-Saharan Africa was established, providing an overview of the capacity to conduct clinical trials for TB vaccine candidates (http://www.edctp.org/our-work/coordination-tb-vaccine-funded-research/directory-tb-vaccine-clinical-trial-sites-sub-saharan-africa/).The directory is intended for clinical triallists, funders, policymakers, and researchers to accelerate the clinical development of novel TB vaccines by providing useful information.Regular updates are necessary to ensure the directory remains relevant for vaccine development and feeds into the continental Clinical Trials Community (https://ctc.africa/).

Vaccination against RSV infections - update and perspective

Almost 60 years after a disastrous clinical vaccine trial in children, which resulted in enhanced disease and even deaths, the world of RSV vaccination is currently undergoing a dramatic positive change and development, closely linked to advances in new vaccine technologies. Three licensed safe and highly efficacious vaccines, Abrysvo, Arexvy and mRESVIA, reduce the incidence of RSV lower respiratory disease by 80% in people older than 60 years of age. Questions regarding long-term protection and effectiveness in specific risk groups with chronic medical conditions remain, and furthermore, innovative and safe concepts to actively vaccinate pregnant women and infants to prevent severe RSV infections - also in these high-risk populations - are eagerly awaited.Passive vaccination with the long-acting monoclonal antibody Nirsevimab for prevention of severe disease in the first RSV season of infants is a major innovation in global health and the importance and benefits of reducing the number of intramuscular injections for high-risk children is immense. In the coming years, results of numerous pediatric candidate RSV vaccine studies are expected, although particular caution seems advisable for historical reasons. In summary, the field of RSV vaccination has been revolutionized in the last 2 years and we will see further significant progress soon.

Pooled safety evaluation for a new single-shot live-attenuated chikungunya vaccine.

Chikungunya disease, caused by chikungunya virus (CHIKV), is associated with substantial morbidity, including debilitating CHIKV-related arthralgia. Three clinical trials of a CHIKV vaccine (VLA1553, IXCHIQ®) were conducted in the US: a Phase 1 dose-finding trial, a pivotal Phase 3 trial, and a Phase 3 lot-to-lot consistency trial. Participants were healthy adults (≥18 years) and received a single intramuscular dose of VLA1553 (3520 participants) or placebo (1033 participants). Solicited injection site and systemic adverse events (AEs) (10 to 14 days post-vaccination), unsolicited AEs (28 and 180 days post-vaccination), AEs of special interest (AESIs) (28 days post-vaccination), medically attended AEs (MAAEs), serious AEs (SAEs) (180 days post-vaccination), and pregnancies were evaluated. Safety data were pooled, and analyses were descriptive. Overall, 63.7% of participants receiving VLA1553 experienced AEs, (44.7% for placebo), that were generally mild. Solicited injection site AEs, solicited systemic AEs, and unsolicited (Day 29) AEs were reported by 15.5%, 50.9%, 22.7% of participants who received VLA1553 and 11.1%, 26.9%, 13.4% who received placebo. Arthralgia was reported by 16.7% of participants who received VLA1553 and 4.8% of participants who received placebo; none required medical attention. MAAEs, AESIs, and SAEs were reported by 12.4%, 0.3%, 1.5% of participants who received VLA1553 and 11.3%, 0.1%, 0.8% of participants who received placebo. Protocol-defined AESIs were mild and short-lived, and two VLA1553-related SAEs resolved without sequelae. There were no clinically important differences in AE incidence based on age or medical history, and no VLA1553-related adverse pregnancy outcomes. There were 3 deaths (2 in the VLA1553 group and 1 in the placebo group), none was vaccine-related. A single dose of VLA1553 presented with an excellent local tolerability profile and overall safety in line with that expected for a live-attenuated vaccine. The safety profile was comparable in participants aged 18-64 years and ≥65 years.

Incidence of Relapses After Meningococcal Vaccination in Clinical Trials of Eculizumab and Ravulizumab in Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD)

Incidence of Relapses After Meningococcal Vaccination in Clinical Trials of Eculizumab and Ravulizumab in Anti-Aquaporin-4 Antibody-Positive (AQP4-Ab+) Neuromyelitis Optica Spectrum Disorder (NMOSD)

Prophylaxis of respiratory syncytial virus infection: current status and prospects for vaccine development

INTRODUCTION. Respiratory syncytial virus (RSV) is one of the most widespread pathogens that typically cause acute upper and lower respiratory tract infections in children and adults. Monoclonal antibody products have long been used for passive immunoprophylaxis in premature infants with bronchopulmonary dysplasia. However, vaccines have recently been licensed for the prophylactic immunisation of older adults with various risk factors for severe RSV infection (primarily, chronic cardiovascular and respiratory diseases and diabetes mellitus).AIM. This study aimed to review the current status of the development of vaccines for active immunisation against RSV infection, including the epidemiological rationale for their development, clinical trial results for licensed vaccines, recommendations for vaccination, and promising pipeline vaccines for RSV prevention.DISCUSSION. Initially hindered by the unique immunopathogenesis of RSV infection and the genetic hypervariability of RSV for a long time, attempts to develop an RSV vaccine succeeded when international researchers managed to identify a conservative neutralising antibody target capable of inducing specific immunity against RSV. This target, the RSV capsid protein stabilised in its prefusion (pre-F) conformation, can mediate viral entry into the cell following a conformational change. Several subunit vaccines based on recombinant pre-F proteins have successfully passed clinical trials and have been approved for the immunisation of older adults. In addition, one of these vaccines has been recommended for use during pregnancy to prevent RSV infection in newborns and infants. Currently, programmes are being implemented to develop novel RSV vaccines based on messenger RNA (mRNA) and non-replicating attenuated influenza vectors. This article examines and summarises the efficacy and safety parameters of two RSV vaccines approved in multiple countries around the world. Both vaccines have satisfactory safety profiles and comparable prophylactic efficacy parameters.CONCLUSIONS. Prelicensure clinical trials of novel RSV vaccines, including those being developed in the Russian Federation, should include prophylactic efficacy assessments in target patient populations. For vaccines approved by leading international regulators, clinical trials required for approval in the Russian Federation will be limited to bridging studies confirming the immunogenicity and safety of the vaccines.

Novel vaccines against lung cancer.

Despite recent advances in immunotherapy treatment for metastatic, early-stage nonsmall cell lung cancer (NSCLC), palliative, adjuvant, neoadjuvant, and perioperative treatment options, further development is needed. Exploring new frontiers of immuno-oncology is necessary. Researchers are interested in a therapeutic vaccination model. In this paper, we provide a review of the latest lung cancer therapeutic vaccines.We describe strategies for antigen selection and delivery platforms. As of 5th of August 2024, we have reviewed ongoing clinical trials and results.We summarize most of the important clinical trials of novel vaccines, the way of action, and available clinical data. We also discuss the pros and cons of various types of therapeutic vaccines. Until recently, clinical trial results were mixed regarding the efficacy of therapeutic vaccines in lung cancer.Developing next-generation sequencing and bioinformatic technologies has helped identify suitable antigens. New personalized vaccines are based on neoantigens specific to unique tumor mutations.Neoantigens, instead of tumor-associated antigens, better delivery systems and adjuvants will improve antigen presentation and immune system activation.Combining these therapeutic vaccines with other therapeutic approaches will improve and prolong the response.

COVID-19 Vaccine mRNA Biodistribution: Maternal and Fetal Exposure Risks.

SARS-CoV-2 infection during pregnancy has severe consequences on maternal and neonatal health. Presently, vaccination stands as a critical preventive measure for mitigating infection-related risks. Although the initial clinical trials for the COVID-19 vaccines excluded pregnant women, subsequent investigations have indicated mRNA vaccinations' effectiveness and short-term safety during pregnancy. However, there is a lack of information regarding the potential biodistribution of the vaccine mRNA during pregnancy and lactation. Recent findings indicate that COVID-19 vaccine mRNA has been detected in breast milk, suggesting that its presence is not confined to the injection site and raises the possibility of similar distribution to the placenta and the fetus. Furthermore, the potential effects and responses of the placenta and fetus to the vaccine mRNA are still unknown. While potential risks might exist with the exposure of the placenta and fetus to the COVID-19 mRNA vaccine, the application of mRNA therapies for maternal and fetal conditions offers a groundbreaking prospect. Future research should leverage the unique opportunity provided by the first-ever application of mRNA vaccines in humans to understand their biodistribution and impact on the placenta and fetus in pregnant women. Such insights could substantially advance the development of safer and more effective future mRNA-based therapies during pregnancy.

Navigating the Landscape of B Cell Mediated Immunity and Antibody Monitoring in SARS-CoV-2 Vaccine Efficacy: Tools, Strategies and Clinical Trial Insights

Correlates of Protection (CoP) are biomarkers above a defined threshold that can replace clinical outcomes as primary endpoints, predicting vaccine effectiveness to support the approval of new vaccines or follow up studies. In the context of COVID-19 vaccination, CoPs can help address challenges such as demonstrating vaccine effectiveness in special populations, against emerging SARS-CoV-2 variants or determining the durability of vaccine-elicited immunity. While anti-spike IgG titres and viral neutralising capacity have been characterised as CoPs for COVID-19 vaccination, the contribution of other components of the humoral immune response to immediate and long-term protective immunity is less well characterised. This review examines the evidence supporting the use of CoPs in COVID-19 clinical vaccine trials, and how they can be used to define a protective threshold of immunity. It also highlights alternative humoral immune biomarkers, including Fc effector function, mucosal immunity, and the generation of long-lived plasma and memory B cells and discuss how these can be applied to clinical studies and the tools available to study them.

Natural TCRs targeting KRASG12V display fine specificity and sensitivity to human solid tumors.

Neoantigens derived from KRASMUT have been described, but the fine antigen specificity of T cell responses directed against these epitopes are poorly understood. Here, we explore KRASMUT immunogenicity and the properties of 4 TCRs specific for KRASG12V restricted to HLA-A3 superfamily of class I alleles. A phase I clinical vaccine trial targeting KRASMUT was conducted. TCRs targeting KRASG12V restricted to HLA-A*03:01 or HLA-A*11:01 were isolated from vaccinated patients or healthy individuals. A comprehensive analysis of TCR antigen specificity, affinity, cross-reactivity, and CD8 coreceptor dependence was performed. TCR lytic activity was evaluated, and target antigen density was determined by quantitative immunopeptidomics. Vaccination against KRASMUT resulted in the priming of CD8+ and CD4+ T cell responses. KRASG12V -specific natural (not affinity-enhanced) TCRs exhibited exquisite specificity to mutated protein with no discernable reactivity against KRASWT. TCR-recognition motifs were determined and used to identify and exclude cross-reactivity to non-cognate peptides derived from the human proteome. Both HLA-A*03:01 and HLA-A*11:01 restricted TCR-redirected CD8+ T cells exhibited potent lytic activity against KRASG12V cancers, while only HLA-A*11:01 restricted TCR-T CD4+ T cells exhibited anti-tumor effector functions consistent with partial co-receptor dependence. All KRASG12V-specific TCRs displayed high sensitivity for antigen as demonstrated by their ability to eliminate tumor cell lines expressing low levels of of peptide/HLA (4.4 to 242) complexes per cell. This study identifies KRASG12V-specific TCRs with high therapeutic potential for the development of TCR-T cell therapies. gov NCT03592888. AACR SU2C / Lustgarten Foundation, Parker Institute for Cancer Immunotherapy, and NIH (R01 CA204261, P01 CA217805, P30 CA016520).

Comparison of the immunogenicity of mRNA-encoded and protein HIV-1 Env-ferritin nanoparticle designs.

Nucleoside-modified mRNA technology has revolutionized vaccine development with the success of mRNA COVID-19 vaccines. We used modified mRNA technology for the design of envelopes (Env) to induce HIV-1 broadly neutralizing antibodies (bnAbs). However, unlike SARS-CoV-2 neutralizing antibodies that are readily made, HIV-1 bnAb induction is disfavored by the immune system because of the rarity of bnAb B cell precursors and the cross-reactivity of bnAbs targeting certain Env epitopes with host molecules, thus requiring optimized immunogen design. The use of protein nanoparticles (NPs) has been reported to enhance B cell germinal center responses to HIV-1 Env. Here, we report our experience with the expression of Env-ferritin NPs compared with membrane-bound Env gp160 when encoded by modified mRNA. We found that well-folded Env-ferritin NPs were a minority of the protein expressed by an mRNA design and were immunogenic at 20 µg but minimally immunogenic in mice at 1 µg dose in vivo and were not expressed well in draining lymph nodes (LNs) following intramuscular immunization. In contrast, mRNA encoding gp160 was more immunogenic than mRNA encoding Env-NP at 1 µg dose and was expressed well in draining LN following intramuscular immunization. Thus, analysis of mRNA expression in vitro and immunogenicity at low doses in vivo are critical for the evaluation of mRNA designs for optimal immunogenicity of HIV-1 immunogens.IMPORTANCEAn effective HIV-1 vaccine that induces protective antibody responses remains elusive. We have used mRNA technology for designs of HIV-1 immunogens in the forms of membrane-bound full-length envelope gp160 and envelope ferritin nanoparticle. Here, we demonstrated in a mouse model that the membrane-bound form induced a better response than envelope ferritin nanoparticle because of higher in vivo protein expression. The significance of our research is in highlighting the importance of analysis of mRNA design expression and low-dose immunogenicity studies for HIV-1 immunogens before moving to vaccine clinical trials.

Assessment of the current state of pharmaceutical development of anti-staphylococcal prophylactic drugs

Infection caused by Staphylococcus aureus is the most common infection leading to the development of serious complications in humans. S. aureus is among the highly lethal bacteremia-associated pathogens with a mortality rate of approximately 18% in industrial countries; in developing countries, the rate is even higher, up to 27%. One of the most striking and challenging aspects of clinical manifestations caused by S. aureus is the ability of the bacterium to develop resistance to antibiotics. The development of alternative treatment options for staphylococcal infection is urgently needed. The use of immunotherapy and immunoprophylaxis to activate the anti-infection immune response in patients should be considered as a promising direction. Objective: to analyze the main trends in the development of vaccines aimed at the prevention of S. aureus infection and its virulence factors. The present review discusses vaccine development in recent years aimed at preventing infection caused by S. aureus. Particular attention is paid to pathogenicity factors (such as capsule, surface proteins and enzymes) that may be useful for the development of new candidate vaccines or immune therapeutics. In recent years, numerous clinical trials of candidate vaccines based on different antigens, taking into account particularly relevant S. aureus pathogenicity factors that influence morbidity, have not been successful due to their low efficacy or insufficiently substantiated safety (development of adverse events). One of the most important factors constraining vaccine development is the lack of successful translation of vaccine protective activity, which is observed in preclinical studies in experimental models but not confirmed in clinical trials. Therefore, according to numerous researchers, the use of multiple antigens in vaccine formulations should be considered with the focus on different mechanisms of S. aureus pathogenicity and the use of adjuvants.

Collecting and reporting adverse events in low-income settings—perspectives from vaccine trials in the Gambia

BackgroundDespite Africa’s significant infectious disease burden, it is underrepresented in global vaccine clinical trials. While this trend is slowly reversing, it is important to recognize and mitigate the challenges that arise when conducting vaccine clinical trials in this environment. These challenges stem from a variety of factors peculiar to the population and may negatively impact adverse event collection and reporting if not properly addressed.MethodsAs a team of clinical researchers working within the MRCG (Medical Research Council Unit The Gambia), we have conducted 12 phase 1 to 3 vaccine trials over the past 10 years. In this article, we discuss the challenges we face and the strategies we have developed to improve the collection and reporting of adverse events in low-income settings.Outcome.Healthcare-seeking behaviors in the Gambia are influenced by spiritual and cultural beliefs as well as barriers to accessing orthodox healthcare; participants in trials may resort to non-orthodox care, reducing the accuracy of reported adverse events. To address this, trial eligibility criteria prohibit self-treatment and herbal product use during trials. Instead, round-the-clock care is provided to trial participants, facilitating safety follow-up.Constraints in the healthcare system in the Gambia such as limitations in diagnostic tools limit the specificity of diagnosis when reporting adverse events. To overcome these challenges, the Medical Research Council Unit maintains a Clinical Services Department, offering medical care and diagnostic services to study participants.Sociocultural factors, including low literacy rates and social influences, impact adverse event collection. Solicited adverse events are collected during home visits on paper-based or electronic report forms.Community engagement meetings are held before each study starts to inform community stakeholders about the study and answer any questions they may have. These meetings ensure that influential members of the community understand the purpose of the study and the risks and benefits of participating in the trial. This understanding makes them more likely to support participation within their communities.ConclusionConducting ethical vaccine clinical trials in resource-limited settings requires strategies to accurately collect and report adverse events. Our experiences from the Gambia offer insights into adverse event collection in these settings.

Clinical trial transparency and disclosure from the medical writing perspective

It’s been more than 6 years since our last Medical Writing edition dedicated to clinical trial transparency and disclosure. Since then, we have seen the full implementation of the long-awaited EU Clinical Trials Regulation (CTR), the pause and restart of EMA Policy 0070, and of course a global pandemic which resulted in a world-wide surge in freedom of information requests for Covid-19 vaccine clinical trial data. Although many of the regulations and policies governing public disclosure of clinical trial data and documents remain unchanged, we have seen significant changes in the way these are implemented. As those of us who work in this field know all too well, the landscape is ever changing, and it is essential to keep up to date with those changes. Resources such as the Drug Information Association Clinical Trial Disclosure Community, PHUSE Data Transparency Working Group, and Clarity and Openness in Reporting-E3 based (CORE) Reference provide invaluable updates and insights. This issue of Medical Writing touches on a number of different aspects of clinical trial transparency and disclosure, all of which involve medical writers as key stakeholders

Patterns and predictors of COVID-19 vaccination among young adults at 44 US sites: Secondary analysis of a randomized, controlled, open-label trial, March – December 2021

Background: The introduction of vaccines during the COVID-19 pandemic provided an opportunity to slow transmission of SARS-CoV-2, but initial uptake of COVID-19 vaccination was slow. We analyzed data from a randomized clinical trial of the mRNA-1273 vaccine (NCT04811664) to describe the patterns of uptake of COVID-19 vaccines among young adults.Methods: The CoVPN 3006 trial randomized adults ages 18–29 from 44 sites in the United States to receive 1) immediate mRNA-1273 vaccination from the study site, or 2) standard of care, including the option to seek vaccination at any time in the future. Randomization occurred between March and November 2021, and an observational arm of adults who declined vaccination was enrolled beginning June 2021. Among participants in the standard of care (SoC) or Vaccine Declined arms, we estimated demographic, behavioral, and health history correlates of vaccination, and the four-month cumulative incidence of COVID-19 vaccination using inverse probability weighted Kaplan-Meier estimators.Results: Among 728 SoC and 470 Vaccine Declined participants, 79% and 16% received COVID-19 vaccination, respectively. SoC and Vaccine Declined participants were more likely to seek and receive vaccination if they reported COVID-19 preventive behaviors, including wearing masks, physically distancing, and avoiding large gatherings. We identified strong predictors of vaccination in the Vaccine Declined arm, including attending class in person (adjusted risk ratio [aRR]: 0.47, 95% confidence interval [CI] 0.21, 1.03), having a COVID-19 relevant medical condition (aRR: 1.95, 95% CI: 0.89, 4.26), and avoiding large gatherings (aRR: 2.24, 95% CI: 1.18, 4.25), though low vaccination rates in this arm led to imprecise estimates.Conclusions: Individuals who initially decline vaccination can be convinced to vaccinate, particularly if they are already practicing other forms of COVID-19 prevention. Continued outreach and education from the scientific community can combat low vaccine confidence.