The COVID-19 Vaccine in Clinical Trials: Where Are We Now?
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ABSTRACT:
SUBMITTER: Jiang H
PROVIDER: S-EPMC8057314 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Several vaccine candidates to protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 (COVID-19) have entered or will soon enter large-scale, phase 3, placebo-controlled randomized clinical trials. To facilitate harmonized evaluation and comparison of the efficacy of these vaccines, a general set of clinical endpoints is proposed, along with considerations to guide the selection of the primary endpoints on the basis of clinical and statistical reasoning. The plausibility that vaccine protection against symptomatic COVID-19 could be accompanied by a shift toward more SARS-CoV-2 infections that are asymptomatic is highlighted, as well as the potential implications of such a shift.
| S-EPMC7596738 | biostudies-literature
Project description:To speed the development of vaccines against SARS-CoV-2, the United States Federal Government has funded multiple phase 3 trials of candidate vaccines. A single 11-member data and safety monitoring board (DSMB) monitors all government-funded trials to ensure coordinated oversight, promote harmonized designs, and allow shared insights related to safety across trials. DSMB reviews encompass 3 domains: (1) the conduct of trials, including overall and subgroup accrual and data quality and completeness; (2) safety, including individual events of concern and comparisons by randomized group; and (3) interim analyses of efficacy when event-driven milestones are met. Challenges have included the scale and pace of the trials, the frequency of safety events related to the combined enrollment of over 100 000 participants, many of whom are older adults or have comorbid conditions that place them at independent risk of serious health events, and the politicized environment in which the trials have taken place.
| S-EPMC8240876 | biostudies-literature
Project description:Large-scale deployment of COVID-19 vaccines will seriously affect the ongoing phases 2 and 3 randomised placebo-controlled trials assessing SARS-CoV-2 vaccine candidates. The effect will be particularly acute in high-income countries where the entire adult or older population could be vaccinated by late 2021. Regrettably, only a small proportion of the population in many low-income and middle-income countries will have access to available vaccines. Sponsors of COVID-19 vaccine candidates currently in phase 2 or initiating phase 3 trials in 2021 should consider continuing the research in countries with limited affordability and availability of COVID-19 vaccines. Several ethical principles must be implemented to ensure the equitable, non-exploitative, and respectful conduct of trials in resource-poor settings. Once sufficient knowledge on the immunogenicity response to COVID-19 vaccines is acquired, non-inferiority immunogenicity trials-comparing the immune response of a vaccine candidate to that of an authorised vaccine-would probably be the most common trial design. Until then, placebo-controlled, double-blind, crossover trials will continue to play a role in the development of new vaccine candidates. WHO or the Council for International Organizations of Medical Sciences should define an ethical framework for the requirements and benefits for trial participants and host communities in resource-poor settings that should require commitment from all vaccine candidate sponsors from high-income countries.
| S-EPMC8131060 | biostudies-literature
Project description:In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, virus genetic variants are still circulating among vaccinated individuals with different symptomatology disease cases. Understanding the protective or disease associated mechanisms in vaccinated individuals is relevant to advance in vaccine development and implementation. To address this objective, serum protein profiles were characterized by quantitative proteomics and data analysis algorithms in four cohorts of vaccinated individuals uninfected and SARS-CoV-2 infected with asymptomatic, nonsevere and severe disease symptomatology. The results showed that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective or disease associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In nonsevere cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins including the Spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.
2022-10-14 | PXD031969 | Pride
Project description:Due to the COVID-19 infection, which was recognized as a global pandemic by the WHO on March 11, 2020, the number of cases and disease-related deaths increases day by day globally. For this reason, antiviral agents used in treatment and vaccines, the most effective weapon in prevention, continue to be the most popular topic of the plan. Several situations are expected to affect the course of the pandemic. The loss of the ability of the virus to mutate and cause disease, the fact that those who become immunized by having the disease in the society reach a critical rate and create social immunity (herd immunity), and the provision of social immunity with effective vaccination can be counted as some of these situations. Candidate vaccines in the clinical phase among RNA-based vaccines: This review aimed to examine COVID-19 vaccine candidates using RNA technology and compile its current data. We used PubMed, Google Scholar, and World Health Organization (WHO) databases. Also, we followed up on the latest news and developments on vaccine companies’ websites. Conclusion: Vaccination trials, which started due to the seriousness and urgency of the situation that we are in, continue exceptionally quickly and effectively. As per the WHO›s data on July 9, 2021, there have been 291 vaccine trials, 107 of which are in the clinical phase, and 18 (16%) of the vaccine candidates in the clinical phase are RNA-based vaccines. Also, the number of RNA-based vaccines with ongoing preclinical trials is 2
| S-EPMC8771051 | biostudies-literature
Project description:BackgroundVaccine clinical trials should strive to recruit a racially, socioeconomically, and ethnically diverse range of participants to ensure appropriate representation that matches population characteristics. Yet, full inclusion in research is often limited.MethodsA single-center retrospective study was conducted of adults enrolled at Brigham and Women's Hospital (Boston, MA) between July 2020 and December 2021. Demographic characteristics, including age, race, ethnicity, ZIP code, and sex assigned at birth, were analyzed from both HIV and COVID-19 vaccine trials during the study period, acknowledging the limitations to representation under these parameters. We compared the educational attainment of vaccine trial participants to residents of the Massachusetts metropolitan area, geocoded participants' addresses to their census block group, and linked them to reported median household income levels from publicly available data for 2020. Frequency and quartile analyses were carried out, and spatial analyses were performed using ArcGIS Online web-based mapping software (Esri).ResultsA total of 1030 participants from four COVID-19 vaccine trials (n = 916 participants) and six HIV vaccine trials (n = 114 participants) were included in the analysis. The median age was 49 years (IQR 33-63) and 28 years (IQR 24-34) for the COVID-19 and HIV vaccine trials, respectively. Participants identifying as White were the majority group represented for both the COVID-19 (n = 598, 65.3%) and HIV vaccine trials (n = 83, 72.8%). Fewer than 25% of participants identified as Hispanic or Latin. Based on ZIP code of residence, the median household income for COVID-19 vaccine clinical trial participants (n = 846) was 102,088 USD (IQR = 81,442-126,094). For HIV vaccine clinical trial participants (n = 109), the median household income was 101,266 USD (IQR 75,052-108,832).ConclusionWe described the characteristics of participants enrolled for HIV and COVID-19 vaccine trials at a single center and found similitude in geographical distribution, median incomes, and proportion of underrepresented individuals between the two types of vaccine candidate trials. Further outreach efforts are needed to ensure the inclusion of individuals from lower educational and socioeconomic brackets. In addition, continued and sustained efforts are necessary to ensure inclusion of individuals from diverse racial and ethnic backgrounds.
| S-EPMC11311253 | biostudies-literature
Project description:IntroductionCommunities of color have faced disproportionate morbidity and mortality from COVID-19, coupled with historical underrepresentation in US clinical trials, creating challenges for equitable participation in developing and testing a safe and effective COVID-19 vaccine.MethodsTo increase diversity, including racial and ethnic representation, in local Los Angeles County NIH-sponsored Phase 3 SARS-CoV-2 vaccine clinical trials, we used deliberative community engagement approaches to form a Community Consultant Panel (CCP) that partnered with trial research teams. Thirteen members were recruited, including expertise from essential workers, community-based and faith-based organizations, or leaders from racial and ethnic minority communities.ResultsWorking closely with local investigators for the vaccine studies, the CCP provided critical insight on best practices for community trust building, clinical trial participation, and reliable information dissemination regarding COVID-19 vaccines. Modifying recruitment, outreach, and trial protocols led to majority-minority participants (55%-78%) in each of the three vaccine clinical trials. CCP's input led to cultural tailoring of recruitment materials, changes in recruitment messaging, and supportive services to improve trial accessibility and acceptability (transportation, protocols for cultural competency, and support linkages to care in case of an adverse event). Barriers to clinical trial participation unable to be resolved included childcare, requests for after-hours appointment availability, and mobile locations for trial visits.ConclusionUsing deliberative community engagement can provide critical and timely insight into the community-centered barriers to COVID-19 vaccine trial participation, including addressing social determinants of health, trust, clinical trial literacy, structural barriers, and identifying trusted messenger and reliable sources of information.
| S-EPMC9874035 | biostudies-literature
Project description:Children usually present with milder symptoms of COVID-19 as compared with adults. Supportive care alone is appropriate for most children with COVID-19. Antiviral therapy may be required for those with severe or critical diseases. Currently there has been a rapid development of vaccines globally to prevent COVID-19 and several vaccines are being evaluated in children and adolescents. Currently, only the Pfizer-BioNTech messenger RNA vaccine is approved for emergency authorization use in the pediatric population ages 16 years and older.
| S-EPMC8130516 | biostudies-literature
Project description:IntroductionThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has currently caused the pandemic with a high progressive speed and has been considered as the global public health crisis in 2020. This new member of the coronavirus family has created a potentially fatal disease, called coronavirus disease-2019 (COVID-19). Despite the continuous efforts of researchers to find effective vaccines and drugs for COVID-19, there is still no success in this matter.Areas coveredHere, the literature regarding the COVID-19 vaccine candidates currently in the clinical trials, as well as main candidates in pre-clinical stages for development and research, were reviewed. These candidates have been developed under five different major platforms, including live-attenuated vaccine, mRNA-based vaccine, DNA vaccines, inactivated virus, and viral-vector-based vaccine.Expert opinionThere are several limitations in the field of the rapid vaccine development against SARS-CoV-2, and other members of the coronavirus family such as SARS-CoV and MERS-CoV. The key challenges of designing an effective vaccine within a short time include finding the virulence ability of an emerging virus and potential antigen, choosing suitable experimental models and efficient route of administration, the immune-response study, designing the clinical trials, and determining the safety, as well as efficacy.
| S-EPMC7898300 | biostudies-literature
Project description:The SARS-CoV-2 Delta (B.1.617.2) variant is capable of infecting vaccinated persons. An open question remains as to whether deficiencies in specific vaccine-elicited immune responses result in susceptibility to vaccine breakthrough infection. We investigated 55 vaccine breakthrough infection cases (mostly Delta) in Singapore, comparing them against 86 vaccinated close contacts who did not contract infection. Vaccine breakthrough cases showed lower memory B cell frequencies against SARS-CoV-2 receptor binding domain (RBD). Compared to plasma antibodies, antibodies secreted by memory B cells retained a higher fraction of neutralizing properties against the Delta variant. Inflammatory cytokines including IL-1β and TNF were lower in vaccine breakthrough infections than primary infection of similar disease severity, underscoring the usefulness of vaccination in preventing inflammation. This report highlights the importance of memory B cells against vaccine breakthrough, and suggests that lower memory B cell levels may be a correlate of risk for Delta vaccine breakthrough infection.
| S-SCDT-EMM-2021-15227 | biostudies-other