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The Journal of Infectious Diseases Mar 2023The aim of this study was to investigate safety and immunogenicity of vaccine formulations against respiratory syncytial virus (RSV) containing the stabilized prefusion... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The aim of this study was to investigate safety and immunogenicity of vaccine formulations against respiratory syncytial virus (RSV) containing the stabilized prefusion conformation of RSV fusion protein (RSVPreF3).
METHODS
This phase 1/2, randomized controlled, observer-blind study enrolled 48 young adults (YAs; aged 18-40 years) and 1005 older adults (OAs; aged 60-80 years) between January and August 2019. Participants were randomized into equally sized groups to receive 2 doses of unadjuvanted (YAs and OAs) or AS01-adjuvanted (OAs) vaccine or placebo 2 months apart. Vaccine safety and immunogenicity were assessed until 1 month (YAs) or 12 months (OAs) after second vaccination.
RESULTS
The RSVPreF3 vaccines boosted humoral (RSVPreF3-specific immunoglobulin G [IgG] and RSV-A neutralizing antibody) responses, which increased in an antigen concentration-dependent manner and were highest after dose 1. Compared to prevaccination, the geometric mean frequencies of polyfunctional CD4+ T cells increased after each dose and were significantly higher in adjuvanted than unadjuvanted vaccinees. Postvaccination immune responses persisted until end of follow-up. Solicited adverse events were mostly mild to moderate and transient. Despite a higher observed reactogenicity of AS01-containing vaccines, no safety concerns were identified for any assessed formulation.
CONCLUSIONS
Based on safety and immunogenicity profiles, the AS01E-adjuvanted vaccine containing 120 μg of RSVPreF3 was selected for further clinical development.
CLINICAL TRIALS REGISTRATION
NCT03814590.
Topics: Young Adult; Humans; Aged; Respiratory Syncytial Virus Vaccines; Antibodies, Viral; Respiratory Syncytial Virus Infections; Antibodies, Neutralizing; Respiratory Syncytial Virus, Human; Immunogenicity, Vaccine
PubMed: 35904987
DOI: 10.1093/infdis/jiac327 -
Vaccine Jun 2017Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide... (Review)
Review
Case-control studies are commonly used to evaluate effectiveness of licensed vaccines after deployment in public health programs. Such studies can provide policy-relevant data on vaccine performance under 'real world' conditions, contributing to the evidence base to support and sustain introduction of new vaccines. However, case-control studies do not measure the impact of vaccine introduction on disease at a population level, and are subject to bias and confounding, which may lead to inaccurate results that can misinform policy decisions. In 2012, a group of experts met to review recent experience with case-control studies evaluating the effectiveness of several vaccines; here we summarize the recommendations of that group regarding best practices for planning, design and enrollment of cases and controls. Rigorous planning and preparation should focus on understanding the study context including healthcare-seeking and vaccination practices. Case-control vaccine effectiveness studies are best carried out soon after vaccine introduction because high coverage creates strong potential for confounding. Endpoints specific to the vaccine target are preferable to non-specific clinical syndromes since the proportion of non-specific outcomes preventable through vaccination may vary over time and place, leading to potentially confusing results. Controls should be representative of the source population from which cases arise, and are generally recruited from the community or health facilities where cases are enrolled. Matching of controls to cases for potential confounding factors is commonly used, although should be reserved for a limited number of key variables believed to be linked to both vaccination and disease. Case-control vaccine effectiveness studies can provide information useful to guide policy decisions and vaccine development, however rigorous preparation and design is essential.
Topics: Case-Control Studies; Control Groups; Female; Humans; Immunization Programs; Immunogenicity, Vaccine; Male; Treatment Outcome; Vaccination; Vaccines
PubMed: 28442231
DOI: 10.1016/j.vaccine.2017.04.037 -
Viruses Nov 2022
Topics: Humans; SARS-CoV-2; COVID-19; COVID-19 Vaccines; HIV Infections; Vaccine Development
PubMed: 36560600
DOI: 10.3390/v14122598 -
Viruses Jan 2022In 2014 and 2021, two nucleic-acid vaccine candidates named MAV E2 and VGX-3100 completed phase III clinical trials in Mexico and U.S., respectively, for patients with... (Review)
Review
In 2014 and 2021, two nucleic-acid vaccine candidates named MAV E2 and VGX-3100 completed phase III clinical trials in Mexico and U.S., respectively, for patients with human papillomavirus (HPV)-related, high-grade squamous intraepithelial lesions (HSIL). These well-tolerated but still unlicensed vaccines encode distinct HPV antigens (E2 versus E6+E7) to elicit cell-mediated immune responses; their clinical efficacy, as measured by HSIL regression or cure, was modest when compared with placebo or surgery (conization), but both proved highly effective in clearing HPV infection, which should help further optimize strategies for enhancing vaccine immunogenicity, toward an ultimate goal of preventing malignancies in millions of patients who are living with persistent, oncogenic HPV infection but are not expected to benefit from current, prophylactic vaccines. The major roadblocks to a highly efficacious and practical product remain challenging and can be classified into five categories: (i) getting the vaccines into the right cells for efficient expression and presentation of HPV antigens (fusion proteins or epitopes); (ii) having adequate coverage of oncogenic HPV types, beyond the current focus on HPV-16 and -18; (iii) directing immune protection to various epithelial niches, especially anogenital mucosa and upper aerodigestive tract where HPV-transformed cells wreak havoc; (iv) establishing the time window and vaccination regimen, including dosage, interval and even combination therapy, for achieving maximum efficacy; and (v) validating therapeutic efficacy in patients with poor prognosis because of advanced, recurrent or non-resectable malignancies. Overall, the room for improvements is still large enough that continuing efforts for research and development will very likely extend into the next decade.
Topics: Animals; Cancer Vaccines; Clinical Trials as Topic; Female; Humans; Immunogenicity, Vaccine; Neoplasms; Papillomavirus Infections; Papillomavirus Vaccines; Squamous Intraepithelial Lesions of the Cervix; Uterine Cervical Neoplasms; Vaccine Development; Vaccines, DNA; mRNA Vaccines; Uterine Cervical Dysplasia
PubMed: 35215833
DOI: 10.3390/v14020239 -
Frontiers in Immunology 2023Coronavirus disease (Covid-19) has not only shaped awareness of the impact of infectious diseases on global health. It has also provided instructive lessons for better... (Review)
Review
Coronavirus disease (Covid-19) has not only shaped awareness of the impact of infectious diseases on global health. It has also provided instructive lessons for better prevention strategies against new and current infectious diseases of major importance. Tuberculosis (TB) is a major current health threat caused by (Mtb) which has claimed more lives than any other pathogen over the last few centuries. Hence, better intervention measures, notably novel vaccines, are urgently needed to accomplish the goal of the World Health Organization to end TB by 2030. This article describes how the research and development of TB vaccines can benefit from recent developments in the Covid-19 vaccine pipeline from research to clinical development and outlines how the field of TB research can pursue its own approaches. It begins with a brief discussion of major vaccine platforms in general terms followed by a short description of the most widely applied Covid-19 vaccines. Next, different vaccination regimes and particular hurdles for TB vaccine research and development are described. This specifically considers the complex immune mechanisms underlying protection and pathology in TB which involve innate as well as acquired immune mechanisms and strongly depend on fine tuning the response. A brief description of the TB vaccine candidates that have entered clinical trials follows. Finally, it discusses how experiences from Covid-19 vaccine research, development, and rollout can and have been applied to the TB vaccine pipeline, emphasizing similarities and dissimilarities.
Topics: Humans; COVID-19 Vaccines; COVID-19; Tuberculosis; Tuberculosis Vaccines; Communicable Diseases; Vaccine Development
PubMed: 38035095
DOI: 10.3389/fimmu.2023.1273938 -
Can ChatGPT draft a research article? An example of population-level vaccine effectiveness analysis.Journal of Global Health Feb 2023We reflect on our experiences of using Generative Pre-trained Transformer ChatGPT, a chatbot launched by OpenAI in November 2022, to draft a research article. We aim to...
We reflect on our experiences of using Generative Pre-trained Transformer ChatGPT, a chatbot launched by OpenAI in November 2022, to draft a research article. We aim to demonstrate how ChatGPT could help researchers to accelerate drafting their papers. We created a simulated data set of 100 000 health care workers with varying ages, Body Mass Index (BMI), and risk profiles. Simulation data allow analysts to test statistical analysis techniques, such as machine-learning based approaches, without compromising patient privacy. Infections were simulated with a randomized probability of hospitalisation. A subset of these fictitious people was vaccinated with a fictional vaccine that reduced this probability of hospitalisation after infection. We then used ChatGPT to help us decide how to handle the simulated data in order to determine vaccine effectiveness and draft a related research paper. AI-based language models in data analysis and scientific writing are an area of growing interest, and this exemplar analysis aims to contribute to the understanding of how ChatGPT can be used to facilitate these tasks.
Topics: Humans; Vaccine Efficacy; Computer Simulation; Software; Confidentiality; Health Personnel
PubMed: 36798998
DOI: 10.7189/jogh.13.01003 -
ACS Nano Oct 2020Despite the vital role of vaccines in fighting viral pathogens, effective vaccines are still unavailable for many infectious diseases. The importance of vaccines cannot... (Review)
Review
Despite the vital role of vaccines in fighting viral pathogens, effective vaccines are still unavailable for many infectious diseases. The importance of vaccines cannot be overstated during the outbreak of a pandemic, such as the coronavirus disease 2019 (COVID-19) pandemic. The understanding of genomics, structural biology, and innate/adaptive immunity have expanded the toolkits available for current vaccine development. However, sudden outbreaks and the requirement of population-level immunization still pose great challenges in today's vaccine designs. Well-established vaccine development protocols from previous experiences are in place to guide the pipelines of vaccine development for emerging viral diseases. Nevertheless, vaccine development may follow different paradigms during a pandemic. For example, multiple vaccine candidates must be pushed into clinical trials simultaneously, and manufacturing capability must be scaled up in early stages. Factors from essential features of safety, efficacy, manufacturing, and distributions to administration approaches are taken into consideration based on advances in materials science and engineering technologies. In this review, we present recent advances in vaccine development by focusing on vaccine discovery, formulation, and delivery devices enabled by alternative administration approaches. We hope to shed light on developing better solutions for faster and better vaccine development strategies through the use of biomaterials, biomolecular engineering, nanotechnology, and microfabrication techniques.
Topics: COVID-19 Vaccines; Clinical Trials as Topic; Coronavirus Infections; Humans; Immunogenicity, Vaccine; Vaccine Potency; Vaccines, Subunit; Vaccines, Synthetic; Viral Vaccines
PubMed: 33001626
DOI: 10.1021/acsnano.0c06109 -
Microbial Pathogenesis Dec 2022The ongoing global pandemic of novel coronavirus pneumonia (COVID-19) caused by the SARS-CoV-2 has a significant impact on global health and economy system. In this... (Review)
Review
The ongoing global pandemic of novel coronavirus pneumonia (COVID-19) caused by the SARS-CoV-2 has a significant impact on global health and economy system. In this context, there have been some landmark advances in vaccine development. Over 100 new coronavirus vaccine candidates have been approved for clinical trials, with ten WHO-approved vaccines including four inactivated virus vaccines, two mRNA vaccines, three recombinant viral vectored vaccines and one protein subunit vaccine on the "Emergency Use Listing". Although the SARS-CoV-2 has an internal proofreading mechanism, there have been a number of mutations emerged in the pandemic affecting its transmissibility, pathogenicity and immunogenicity. Of these, mutations in the spike (S) protein and the resultant mutant variants have posed new challenges for vaccine development and application. In this review article, we present an overview of vaccine development, the prevalence of new coronavirus variants and their impact on protective efficacy of existing vaccines and possible immunization strategies coping with the viral mutation and diversity.
Topics: Humans; Antibodies, Viral; COVID-19; COVID-19 Vaccines; Immunogenicity, Vaccine; Mutation; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Vaccine Development; Vaccines, Inactivated
PubMed: 36243381
DOI: 10.1016/j.micpath.2022.105828 -
Human Vaccines & Immunotherapeutics Nov 2021Malaria vaccines hold significant promise for life-saving benefit, especially to children who bear the major burden of malaria mortality. The RTS,S/AS01 malaria vaccine...
Malaria vaccines hold significant promise for life-saving benefit, especially to children who bear the major burden of malaria mortality. The RTS,S/AS01 malaria vaccine provides moderate efficacy and is being tested in implementation studies. In parallel, multiple strategies are being advanced to test next-generation malaria vaccines, including novel approaches that build on principles learned from RTS,S development, vaccination with radiation-attenuated sporozoites, and development of monoclonal antibodies targeting immunogenic peptides. Novel vaccine delivery approaches are also being advanced, including self-amplifying RNA vaccine delivery, self-assembling protein nanoparticle methods, circumsporozoite protein-based approaches, and whole organism vaccination. Techniques employed for COVID-19 vaccine development should also be considered for malaria vaccination, including sustained release polymer nanoparticle hydrogel vaccination and charge-altering releasable transporters. As vaccine science advances and new approaches optimize knowledge gained, highly effective malaria vaccines that provide sustained protection are within reach.
Topics: COVID-19; COVID-19 Vaccines; Child; Humans; Malaria Vaccines; Malaria, Falciparum; Plasmodium falciparum; SARS-CoV-2; Vaccination; Vaccine Development; Vaccines, Synthetic; mRNA Vaccines
PubMed: 34347570
DOI: 10.1080/21645515.2021.1947762 -
Expert Review of Vaccines 2023Fungal infections are caused by a broad range of pathogenic fungi that are found worldwide with different geographic distributions, incidences, and mortality rates.... (Review)
Review
INTRODUCTION
Fungal infections are caused by a broad range of pathogenic fungi that are found worldwide with different geographic distributions, incidences, and mortality rates. Considering that there are relatively few approved medications available for combating fungal diseases and no vaccine formulation commercially available, multiple groups are searching for new antifungal drugs, examining drugs for repurposing and developing antifungal vaccines, in order to control deaths, sequels, and the spread of these complex infections.
AREAS COVERED
This review provides a summary of advances in fungal vaccine studies and the different approaches under development, such as subunit vaccines, whole organism vaccines, and DNA vaccines, as well as studies that optimize the use of adjuvants. We conducted a literature search of the PubMed with terms: fungal vaccines and genus of fungal pathogens (Cryptococcus spp. Candida spp. Coccidioides spp. Aspergillus spp. Sporothrix spp. Histoplasma spp. Paracoccidioides spp. Pneumocystis spp. and the Mucorales order), a total of 177 articles were collected from database.
EXPERT OPINION
Problems regarding the immune response development in an immunocompromised organism, the similarity between fungal and mammalian cells, and the lack of attention by health organizations to fungal infections are closely related to the fact that, at present, there are no fungal vaccines available for clinical use.
Topics: Animals; Humans; Antifungal Agents; Fungi; Mycoses; Vaccines; Vaccine Development; Mammals
PubMed: 37936254
DOI: 10.1080/14760584.2023.2279570