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Frontiers in Immunology 2021is one of the most important human pathogens worldwide. Its high antibiotic resistance profile reinforces the need for new interventions like vaccines in addition to... (Review)
Review
is one of the most important human pathogens worldwide. Its high antibiotic resistance profile reinforces the need for new interventions like vaccines in addition to new antibiotics. Vaccine development efforts against have failed so far however, the findings from these human clinical and non-clinical studies provide potential insight for such failures. Currently, research is focusing on identifying novel vaccine formulations able to elicit potent humoral and cellular immune responses. Translational science studies are attempting to discover correlates of protection using animal models as well as and models assessing efficacy of vaccine candidates. Several new vaccine candidates are being tested in human clinical trials in a variety of target populations. In addition to vaccines, bacteriophages, monoclonal antibodies, centyrins and new classes of antibiotics are being developed. Some of these have been tested in humans with encouraging results. The complexity of the diseases and the range of the target populations affected by this pathogen will require a multipronged approach using different interventions, which will be discussed in this review.
Topics: Adjuvants, Immunologic; Animals; Antigens, Bacterial; Clinical Trials as Topic; Extracellular Vesicles; Glycoconjugates; Gram-Negative Bacteria; Host-Pathogen Interactions; Humans; Immunity, Cellular; Immunity, Humoral; Immunogenicity, Vaccine; In Vitro Techniques; Mice; Models, Animal; Nucleic Acid-Based Vaccines; Periplasm; Recombinant Proteins; Staphylococcal Infections; Staphylococcal Vaccines; Staphylococcus aureus; Translational Science, Biomedical; Vaccine Development; Vaccines, Attenuated; Vaccines, Synthetic
PubMed: 34305945
DOI: 10.3389/fimmu.2021.705360 -
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 -
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 -
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 -
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 -
Viruses Nov 2022
Topics: Humans; SARS-CoV-2; COVID-19; COVID-19 Vaccines; HIV Infections; Vaccine Development
PubMed: 36560600
DOI: 10.3390/v14122598 -
Vaccine Oct 2017
Topics: Biomedical Research; Congresses as Topic; Humans; Vaccine Potency; Vaccines
PubMed: 28826749
DOI: 10.1016/j.vaccine.2017.08.032 -
Clinical Infectious Diseases : An... Aug 2022Pneumococcal conjugate vaccines (PCVs) have significantly reduced pneumococcal disease, but disease from non-PCV serotypes remains. The safety, tolerability, and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Pneumococcal conjugate vaccines (PCVs) have significantly reduced pneumococcal disease, but disease from non-PCV serotypes remains. The safety, tolerability, and immunogenicity of a 20-valent PCV (PCV20) were evaluated.
METHODS
This pivotal phase 3, randomized, double-blind study enrolled adults into 3 age groups (≥60, 50-59, and 18-49 years) at US and Swedish sites. Participants were randomized to receive 1 PCV20 or 13-valent PCV (PCV13) dose. After 1 month, participants aged ≥60 years also received 1 dose of saline or 23-valent polysaccharide vaccine (PPSV23). Safety assessments included local reactions, systemic events, adverse events, serious adverse events, and newly diagnosed chronic medical conditions. Opsonophagocytic activity geometric mean titers 1 month after PCV20 were compared with 13 matched serotypes after PCV13 and 7 additional serotypes after PPSV23 in participants aged ≥60 years; noninferiority was declared if the lower bound of the 2-sided 95% confidence interval for the opsonophagocytic activity geometric mean titer ratio (ratio of PCV20/saline to PCV13/PPSV23 group) was >0.5. PCV20-elicited immune responses in younger participants were also bridged to those in 60-64-year-olds.
RESULTS
The severity and frequency of prompted local reactions and systemic events were similar after PCV20 or PCV13; no safety concerns were identified. Primary immunogenicity objectives were met, with immune responses after PCV20 noninferior to 13 matched serotypes after PCV13 and to 6 additional PPSV23 serotypes in participants aged ≥60 years; serotype 8 missed the statistical noninferiority criterion. PCV20 induced robust responses to all 20 vaccine serotypes across age groups.
CONCLUSIONS
PCV20 was safe and well tolerated, with immunogenicity comparable to that of PCV13 or PPSV23. PCV20 is anticipated to expand protection against pneumococcal disease in adults.
CLINICAL TRIALS REGISTRATION
NCT03760146.
Topics: Adolescent; Adult; Antibodies, Bacterial; Double-Blind Method; Humans; Immunogenicity, Vaccine; Pneumococcal Infections; Pneumococcal Vaccines; Saline Solution; Serogroup; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 34940806
DOI: 10.1093/cid/ciab990 -
ACS Applied Bio Materials Mar 2022This review discusses peptide epitopes used as antigens in the development of vaccines in clinical trials as well as future vaccine candidates. It covers peptides used... (Review)
Review
This review discusses peptide epitopes used as antigens in the development of vaccines in clinical trials as well as future vaccine candidates. It covers peptides used in potential immunotherapies for infectious diseases including SARS-CoV-2, influenza, hepatitis B and C, HIV, malaria, and others. In addition, peptides for cancer vaccines that target examples of overexpressed proteins are summarized, including human epidermal growth factor receptor 2 (HER-2), mucin 1 (MUC1), folate receptor, and others. The uses of peptides to target cancers caused by infective agents, for example, cervical cancer caused by human papilloma virus (HPV), are also discussed. This review also provides an overview of model peptide epitopes used to stimulate non-specific immune responses, and of self-adjuvanting peptides, as well as the influence of other adjuvants on peptide formulations. As highlighted in this review, several peptide immunotherapies are in advanced clinical trials as vaccines, and there is great potential for future therapies due the specificity of the response that can be achieved using peptide epitopes.
Topics: Adjuvants, Immunologic; Animals; Antigens; Cancer Vaccines; Communicable Disease Control; Humans; Neoplasms; Peptides; Vaccine Development; Vaccines, Subunit
PubMed: 35195008
DOI: 10.1021/acsabm.1c01238