-
Drug Discovery Today Feb 2023Given their superior efficacy, rapid engineering, low-cost manufacturing, and safe delivery prospects, mRNA vaccines offer an intriguing alternative to conventional... (Review)
Review
Given their superior efficacy, rapid engineering, low-cost manufacturing, and safe delivery prospects, mRNA vaccines offer an intriguing alternative to conventional vaccination technologies. Several mRNA vaccine platforms targeting infectious diseases and various types of cancer have exhibited beneficial results both in vivo and in vitro. Issues related to mRNA stability and immunogenicity have been addressed. Current mRNA vaccines can generate robust immune responses, without being constrained by the major histocompatibility complex (MHC) haplotype of the recipient. Given that mRNA vaccinations are the only transient genetic information carriers, they are also safe. In this review, we provide an update and overview on mRNA vaccines, including their current state, and the problems that have prevented them from being used in more general therapeutic ways.
Topics: RNA, Messenger; Vaccines, Synthetic; mRNA Vaccines; Vaccine Development
PubMed: 36427779
DOI: 10.1016/j.drudis.2022.103458 -
Frontiers in Immunology 2021The innate immune system represents the first line of defense against influenza viruses, which cause severe inflammation of the respiratory tract and are responsible for... (Review)
Review
The innate immune system represents the first line of defense against influenza viruses, which cause severe inflammation of the respiratory tract and are responsible for more than 650,000 deaths annually worldwide. mRNA vaccines are promising alternatives to traditional vaccine approaches due to their safe dosing, low-cost manufacturing, rapid development capability, and high efficacy. In this review, we provide our current understanding of the innate immune response that uses pattern recognition receptors to detect and respond to mRNA vaccination. We also provide an overview of mRNA vaccines, and discuss the future directions and challenges in advancing this promising therapeutic approach.
Topics: Adaptive Immunity; Humans; Immunity, Innate; Inflammasomes; Influenza Vaccines; Orthomyxoviridae; Toll-Like Receptors; Vaccination; Vaccine Development; mRNA Vaccines
PubMed: 34531860
DOI: 10.3389/fimmu.2021.710647 -
Annali Di Igiene : Medicina Preventiva... 2024The COVID-19 pandemic had a profound impact on vaccines' Research and Development, on vaccines' market, and on immunization programmes and policies. The need to promptly... (Review)
Review
INTRODUCTION
The COVID-19 pandemic had a profound impact on vaccines' Research and Development, on vaccines' market, and on immunization programmes and policies. The need to promptly respond to the health emergency boostered resources' al-location and innovation, while new technologies were made available. Regulatory procedures were revised and expedited, and global production and distribution capacities significantly increased. Aim of this review is to outline the trajectory of research in vaccinology and vaccines' pipeline, highlighting major challenges and opportunities, and projecting future perspectives in vaccine preventables diseases' prevention and control.
STUDY DESIGN
Narrative review.
METHODS
We comprehensively consulted key biomedical databases including "Medline" and "Embase", preprint platforms, including"MedRxiv" and "BioRxiv", clinical trial registries, selected grey literature sources and scientific reports. Further data and insights were collected from experts in the field. We first reflect on the impact that the COVID-19 had on vaccines' Research and Development, regulatory frameworks, and market, we then present updated figures of vaccines pipeline, by different technologies, comparatively highlighting advantages and disadvantages. We conclude summarizing future perspectives in vaccines' development and immunizations strategies, outlining key challenges, knowledge gaps and opportunities for prevention strategies.
RESULTS
COVID-19 vaccines' development has been largely supported by public funding. New technologies and expetited autho-rization and distribution processes allowed to control the pandemic, leading vaccines' market to grow exponentially. In the post-pandemic era investments in prevention are projected to decrease but advancements in technology offer great potential to future immunization strategies. As of 2023, the vaccine pipeline include almost 1,000 candidates, at different Research and Development phase, including innovative recombinant protein vaccines, nucleic acid vaccines and viral vector vaccines. Vaccines' technology platforms development varies by disease. Overall, vaccinology is progressing towards increasingly safe and effective products that are easily manufacturable and swiftly convertible.
CONCLUSIONS
Vaccine research is rapidly evolving, emerging technologies and new immunization models offer public health new tools and large potential to fight vaccines preventables diseases, with promising new platforms and broadened target populations. Real-life data analysis and operational research is needed to evaluate how such potential is exploited in public health practice to improve population health.
Topics: Humans; COVID-19; COVID-19 Vaccines; Vaccine Development; Pandemics; Forecasting; Biomedical Research; Vaccinology; Immunization Programs; Drug Development
PubMed: 38436081
DOI: 10.7416/ai.2024.2614 -
Frontiers in Immunology 2021Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high infectivity, pathogenicity, and variability, is a... (Review)
Review
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high infectivity, pathogenicity, and variability, is a global pandemic that severely affected public health and the world economy. The development of safe and effective vaccines is crucial to the prevention and control of an epidemic. As an emerging technology, mRNA vaccine is widely used for infectious disease prevention and control and has significant safety, efficacy, and high production. It has received support and funding from many pharmaceutical enterprises and becomes one of the main technologies for preventing COVID-19. This review introduces the current status of SARS-CoV-2 vaccines, specifically mRNA vaccines, focusing on the challenges of developing mRNA vaccines against SARS-CoV-2, and discusses the relevant strategies.
Topics: Animals; COVID-19; COVID-19 Vaccines; Humans; SARS-CoV-2; Vaccine Development; Vaccine Efficacy; mRNA Vaccines
PubMed: 35126377
DOI: 10.3389/fimmu.2021.821538 -
Annual Review of Virology Sep 2022Human cytomegalovirus (HCMV) infection, the most common cause of congenital disease globally, affecting an estimated 1 million newborns annually, can result in lifelong... (Review)
Review
Human cytomegalovirus (HCMV) infection, the most common cause of congenital disease globally, affecting an estimated 1 million newborns annually, can result in lifelong sequelae in infants, such as sensorineural hearing loss and brain damage. HCMV infection also leads to a significant disease burden in immunocompromised individuals. Hence, an effective HCMV vaccine is urgently needed to prevent infection and HCMV-associated diseases. Unfortunately, despite more than five decades of vaccine development, no successful HCMV vaccine is available. This review summarizes what we have learned from acquired natural immunity, including innate and adaptive immunity; the successes and failures of HCMV vaccine human clinical trials; the progress in related animal models; and the analysis of protective immune responses during natural infection and vaccination settings. Finally, we propose novel vaccine strategies that will harness the knowledge of protective immunity and employ new technology and vaccine concepts to inform next-generation HCMV vaccine development.
Topics: Adaptive Immunity; Animals; Cytomegalovirus; Cytomegalovirus Infections; Cytomegalovirus Vaccines; Humans; Immunity, Innate; Infant, Newborn; Vaccine Development
PubMed: 35704747
DOI: 10.1146/annurev-virology-100220-010653 -
Frontiers in Cellular and Infection... 2022is a zoonotic pathogen responsible for the human disease Q fever. While an inactivated whole cell vaccine exists for this disease, its widespread use is precluded by a... (Review)
Review
is a zoonotic pathogen responsible for the human disease Q fever. While an inactivated whole cell vaccine exists for this disease, its widespread use is precluded by a post vaccination hypersensitivity response. Efforts for the development of an improved Q fever vaccine are intricately connected to the availability of appropriate animal models of human disease. Accordingly, small mammals and non-human primates have been utilized for vaccine-challenge and post vaccination hypersensitivity modeling. Here, we review the animal models historically utilized in Q fever vaccine development, describe recent advances in this area, discuss the limitations and strengths of these models, and summarize the needs and criteria for future modeling efforts. In summary, while many useful models for Q fever vaccine development exist, there remains room for growth and expansion of these models which will in turn increase our understanding of host interactions.
Topics: Animals; Bacterial Vaccines; Coxiella burnetii; Mammals; Models, Animal; Q Fever; Vaccine Development
PubMed: 35223553
DOI: 10.3389/fcimb.2022.828784 -
Nature Cancer 2020The need to address COVID-19 is placing huge demands on biomedical research and regulatory processes. Under pressure, it is essential to uphold high bioethical...
The need to address COVID-19 is placing huge demands on biomedical research and regulatory processes. Under pressure, it is essential to uphold high bioethical principles and rigorous standards for the development and approval of medicines.
Topics: Biomedical Research; COVID-19; COVID-19 Vaccines; Humans; SARS-CoV-2; Trust; Vaccine Development
PubMed: 32935085
DOI: 10.1038/s43018-020-00123-2 -
Viruses May 2021Hepatitis C virus (HCV) is a serious and growing public health problem despite recent developments of antiviral therapeutics. To achieve global elimination of HCV, an... (Review)
Review
Hepatitis C virus (HCV) is a serious and growing public health problem despite recent developments of antiviral therapeutics. To achieve global elimination of HCV, an effective cross-genotype vaccine is needed. The failure of previous vaccination trials to elicit an effective cross-reactive immune response demands better vaccine antigens to induce a potent cross-neutralizing response to improve vaccine efficacy. HCV E1 and E2 envelope (Env) glycoproteins are the main targets for neutralizing antibodies (nAbs), which aid in HCV clearance and protection. Therefore, a molecular-level understanding of the nAb responses against HCV is imperative for the rational design of cross-genotype vaccine antigens. Here we summarize the recent advances in structural studies of HCV Env and Env-nAb complexes and how they improve our understanding of immune recognition of HCV. We review the structural data defining HCV neutralization epitopes and conformational plasticity of the Env proteins, and the knowledge applicable to rational vaccine design.
Topics: Animals; Antibodies, Neutralizing; Cross Reactions; Epitopes; Genotype; Hepacivirus; Hepatitis C Antibodies; Hepatitis C Antigens; Humans; Mice; Vaccine Development; Vaccine Efficacy; Viral Hepatitis Vaccines
PubMed: 34064532
DOI: 10.3390/v13050833 -
Journal of Visualized Experiments : JoVE Mar 2022Subunit vaccines offer advantages over more traditional inactivated or attenuated whole-cell-derived vaccines in safety, stability, and standard manufacturing. To...
Subunit vaccines offer advantages over more traditional inactivated or attenuated whole-cell-derived vaccines in safety, stability, and standard manufacturing. To achieve an effective protein-based subunit vaccine, the protein antigen often needs to adopt a native-like conformation. This is particularly important for pathogen-surface antigens that are membrane-bound proteins. Cell-free methods have been successfully used to produce correctly folded functional membrane protein through the co-translation of nanolipoprotein particles (NLPs), commonly known as nanodiscs. This strategy can be used to produce subunit vaccines consisting of membrane proteins in a lipid-bound environment. However, cell-free protein production is often limited to small scale (<1 mL). The amount of protein produced in small-scale production runs is usually sufficient for biochemical and biophysical studies. However, the cell-free process needs to be scaled up, optimized, and carefully tested to obtain enough protein for vaccine studies in animal models. Other processes involved in vaccine production, such as purification, adjuvant addition, and lyophilization, need to be optimized in parallel. This paper reports the development of a scaled-up protocol to express, purify, and formulate a membrane-bound protein subunit vaccine. Scaled-up cell-free reactions require optimization of plasmid concentrations and ratios when using multiple plasmid expression vectors, lipid selection, and adjuvant addition for high-level production of formulated nanolipoprotein particles. The method is demonstrated here with the expression of a chlamydial major outer membrane protein (MOMP) but may be widely applied to other membrane protein antigens. Antigen effectiveness can be evaluated in vivo through immunization studies to measure antibody production, as demonstrated here.
Topics: Adjuvants, Immunologic; Animals; Bacterial Outer Membrane Proteins; Chlamydia muridarum; Recombinant Proteins; Vaccine Development
PubMed: 35377358
DOI: 10.3791/63028 -
Biostatistics (Oxford, England) Jul 2023Vaccine trials are generally designed to assess efficacy on clinical disease. The vaccine effect on infection, while important both as a proxy for transmission and to...
Vaccine trials are generally designed to assess efficacy on clinical disease. The vaccine effect on infection, while important both as a proxy for transmission and to describe a vaccine's entire effects, requires frequent (e.g., twice a week) longitudinal sampling to capture all infections. Such sampling may not always be feasible. A logistically easy approach is to collect a sample to test for infection at a regularly scheduled visit. Such point or cross-sectional sampling does not permit estimation of classic vaccine efficacy on infection, as long duration infections are sampled with higher probability. Building on work by Rinta-Kokko and others (2009) and Lipsitch and Kahn (2021), we evaluate proxies of the vaccine effect on transmission at a point in time; the vaccine efficacy on prevalent infection and on prevalent viral load, VE$_{\rm PI}$ and VE$_{\rm PVL}$, respectively. Longer infections with higher viral loads should have more transmission potential and prevalent vaccine efficacy naturally captures this aspect. We demonstrate how these parameters obtain from an underlying proportional hazards model for infection and allow for waning efficacy on infection, duration, and viral load. We estimate these parameters based on regression models with either repeated cross-sectional sampling or frequent longitudinal sampling. We evaluate the methods by simulation and analyze a phase III vaccine trial with polymerase chain reaction (PCR) cross-sectional sampling for subclinical infection.
Topics: Humans; Cross-Sectional Studies; Vaccine Efficacy; Vaccines; Computer Simulation
PubMed: 35296878
DOI: 10.1093/biostatistics/kxac008