Prophylactic vaccine delivery systems against epidemic infectious diseases.
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ABSTRACT:
SUBMITTER: Pan C
PROVIDER: S-EPMC8285224 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT). Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV) etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents.
| S-EPMC4190526 | biostudies-other
Project description:BackgroundThe Coalition for Epidemic Preparedness Innovations was established in 2016, to develop vaccines that can contribute to preparedness for outbreaks of epidemic infectious diseases. Evidence on vaccine development costs for such diseases is scarce. Our goal was to estimate the minimum cost for achieving vaccine research and development preparedness targets in a portfolio of 11 epidemic infectious diseases, accounting for vaccine pipeline constraints and uncertainty in research and development preparedness outcomes.MethodsWe assembled a pipeline of 224 vaccine candidates from preclinical through to phase 2 for 11 priority epidemic infectious diseases. We used a linear regression model to identify drivers of development costs from preclinical through to end of phase 2a. Drawing from published estimates of vaccine research and development probabilities of success, we simulated costs for advancing these 224 vaccine candidates through to the end of phase 2a. We combined these findings to determine minimum costs for progressing at least one vaccine through to the end of phase 2a per epidemic infectious disease by means of a stochastic optimisation model.FindingsThe cost of developing a single epidemic infectious disease vaccine from preclinical trials through to end of phase 2a is US$31-68 million (US$14-159 million range), assuming no risk of failure. We found that previous licensure experience and indirect costs are upward drivers of research and development costs. Accounting for probability of success, the average cost of successfully advancing at least one epidemic infectious disease vaccine through to the end of phase 2a can vary from US$84-112 million ($23 million-$295 million range) starting from phase 2 to $319-469 million ($137 million-$1·1 billion range) starting from preclinical. This cost includes the cumulative cost of failed vaccine candidates through the research and development process. Assuming these candidates and funding were made available, progressing at least one vaccine through to the end of phase 2a for each of the 11 epidemic infectious diseases would cost a minimum of $2·8-3·7 billion ($1·2 billion-$8·4 billion range).InterpretationOur analysis provides new evidence on vaccine research and development pipelines and associated costs for 11 epidemic infectious diseases, highlighting both funding needs and research and development gaps for achieving vaccine research and development preparedness targets.FundingThis work was partly supported by the Research Council of Norway through the Global Health and Vaccination Programme GLOBVAC.
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Project description:Today's world is characterized by increasing population density, human mobility, urbanization, and climate and ecological change. This global dynamic has various effects, including the increased appearance of emerging infectious diseases (EIDs), which pose a growing threat to global health security.Outbreaks of EIDs, like the 2013-2016 Ebola outbreak in West Africa or the current Ebola outbreak in Democratic Republic of the Congo (DRC), have not only put populations in low- and middle-income countries (LMIC) at risk in terms of morbidity and mortality, but they also have had a significant impact on economic growth in affected regions and beyond.The Coalition for Epidemic Preparedness Innovation (CEPI) is an innovative global partnership between public, private, philanthropic, and civil society organizations that was launched as the result of a consensus that a coordinated, international, and intergovernmental plan was needed to develop and deploy new vaccines to prevent future epidemics.CEPI is focusing on supporting candidate vaccines against the World Health Organization (WHO) Blueprint priority pathogens MERS-CoV, Nipah virus, Lassa fever virus, and Rift Valley fever virus, as well as Chikungunya virus, which is on the WHO watch list. The current vaccine portfolio contains a wide variety of technologies, ranging across recombinant viral vectors, nucleic acids, and recombinant proteins. To support and accelerate vaccine development, CEPI will also support science projects related to the development of biological standards and assays, animal models, epidemiological studies, and diagnostics, as well as build capacities for future clinical trials in risk-prone contexts.
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Project description:Since centuries, the rapid spread and cure of infectious diseases have been a major concern to the progress and survival of humans. These diseases are a global burden and the prominent cause for worldwide deaths and disabilities. Nanomedicine has emerged as the most excellent tool to eradicate and halt their spread. Various nanoformulations (NFs) using advanced nanotechnology are in demand. Recently, hydrogel and nanogel based drug delivery devices have posed new prospects to simulate the natural intelligence of various biological systems. Owing to their unique porous interpenetrating network design, hydrophobic drug incorporation and stimulus sensitivity hydrogels owe excellent potential as targeted drug delivery systems. The present review is an attempt to highlight the recent trends of hydrogel based drug delivery systems for the delivery of therapeutic agents and diagnostics for major infectious diseases including acquired immune deficiency syndrome (AIDS), malaria, tuberculosis, influenza and ebola. Future prospects and challenges are also described.
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Project description:The oral cavity is a unique complex ecosystem colonized with huge numbers of microorganism species. Oral cavities are closely associated with oral health and sequentially with systemic health. Many factors might cause the shift of composition of oral microbiota, thus leading to the dysbiosis of oral micro-environment and oral infectious diseases. Local therapies and dental hygiene procedures are the main kinds of treatment. Currently, oral drug delivery systems (DDS) have drawn great attention, and are considered as important adjuvant therapy for oral infectious diseases. DDS are devices that could transport and release the therapeutic drugs or bioactive agents to a certain site and a certain rate in vivo. They could significantly increase the therapeutic effect and reduce the side effect compared with traditional medicine. In the review, emerging recent applications of DDS in the treatment for oral infectious diseases have been summarized, including dental caries, periodontitis, peri-implantitis and oral candidiasis. Furthermore, oral stimuli-responsive DDS, also known as "smart" DDS, have been reported recently, which could react to oral environment and provide more accurate drug delivery or release. In this article, oral smart DDS have also been reviewed. The limits have been discussed, and the research potential demonstrates good prospects.
| S-EPMC7038021 | biostudies-literature
Project description:Due to emergence of new variants of pathogenic micro-organisms the treatment and immunization of infectious diseases have become a great challenge in the past few years. In the context of vaccine development remarkable efforts have been made to develop new vaccines and also to improve the efficacy of existing vaccines against specific diseases. To date, some vaccines are developed from protein subunits or killed pathogens, whilst several vaccines are based on live-attenuated organisms, which carry the risk of regaining their pathogenicity under certain immunocompromised conditions. To avoid this, the development of risk-free effective vaccines in conjunction with adequate delivery systems are considered as an imperative need to obtain desired humoral and cell-mediated immunity against infectious diseases. In the last several years, the use of nanoparticle-based vaccines has received a great attention to improve vaccine efficacy, immunization strategies, and targeted delivery to achieve desired immune responses at the cellular level. To improve vaccine efficacy, these nanocarriers should protect the antigens from premature proteolytic degradation, facilitate antigen uptake and processing by antigen presenting cells, control release, and should be safe for human use. Nanocarriers composed of lipids, proteins, metals or polymers have already been used to attain some of these attributes. In this context, several physico-chemical properties of nanoparticles play an important role in the determination of vaccine efficacy. This review article focuses on the applications of nanocarrier-based vaccine formulations and the strategies used for the functionalization of nanoparticles to accomplish efficient delivery of vaccines in order to induce desired host immunity against infectious diseases.
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Project description:Immersion vaccination is considered as the most effective method for juvenile fish in preventing viral disease, due to its convenience for mass vaccination and stress-free administration. However, immune responses following immersion vaccination are generally less robust and of shorter duration than those induced through intraperitoneal injection. Herein, to improve the efficacy of the immersion vaccine, we constructed a targeted single-walled carbon nanotubes-based immersion vaccine delivery system (CNTs-M-VP7), the surface of which are modified with mannose to allow antigen-presenting cells' (APCs) targeting. The targeting ability of CNTs-M-VP7 was confirmed in vivo and in vitro. Critically, this immersion CNTs-M-VP7 vaccine could cross into the fish body through mucosal tissues (skin, gill, and intestine), and then present to immune-related tissues. Moreover, CNTs-M-VP7 could significantly induce the maturation and presenting process of APCs, which would then trigger robust immune responses. Altogether, this study demonstrates that the single-walled carbon nanotubes (SWCNTs)-based targeted nanovaccine delivery system shows the potential to be an effective prophylactic against fish viral disease.
| S-EPMC7157632 | biostudies-literature
Project description:Prophylactic vaccines capable of preventing human papillomavirus (HPV) infections are still inaccessible to a vast majority of the global population due to their high cost and challenges related to multiple administrations performed in a medical setting. In an effort to improve distribution and administration, we have developed dissolvable microneedles loaded with a thermally stable HPV vaccine candidate consisting of Qβ virus-like particles (VLPs) displaying a highly conserved epitope from the L2 protein of HPV (Qβ-HPV). Polymeric microneedle delivery of Qβ-HPV produces similar amounts of anti-HPV16 L2 IgG antibodies compared to traditional subcutaneous injection while delivering a much smaller amount of intradermal dose. However, a dose sparing effect was found. Furthermore, immunization yielded neutralizing antibody responses in a HPV pseudovirus assay. The vaccine candidate was confirmed to be stable at room temperature after storage for several months, potentially mitigating many of the challenges associated with cold-chain distribution. The ease of self-administration and minimal invasiveness of such microneedle patch vaccines may enable wide-scale distribution of the HPV vaccine and lead to higher patient compliance. The Qβ VLP and its delivery technology is a plug-and-play system that could serve as a universal platform with a broad range of applications. Qβ VLPs may be stockpiled for conjugation to a wide range of epitopes, which are then packaged and delivered directly to the patient via noninvasive microneedle patches. Such a system paves the way for rapid distribution and self-administration of vaccines.
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Project description:Infectious diseases, also known as transmissible or communicable diseases, are caused by pathogens or parasites that spread in communities by direct contact with infected individuals or contaminated materials, through droplets and aerosols, or via vectors such as insects. Such diseases cause ˜17% of all human deaths and their management and control places an immense burden on healthcare systems worldwide. Traditional approaches for the prevention and control of infectious diseases include vaccination programmes, hygiene measures and drugs that suppress the pathogen, treat the disease symptoms or attenuate aggressive reactions of the host immune system. The provision of vaccines and biologic drugs such as antibodies is hampered by the high cost and limited scalability of traditional manufacturing platforms based on microbial and animal cells, particularly in developing countries where infectious diseases are prevalent and poorly controlled. Molecular farming, which uses plants for protein expression, is a promising strategy to address the drawbacks of current manufacturing platforms. In this review article, we consider the potential of molecular farming to address healthcare demands for the most prevalent and important epidemic and pandemic diseases, focussing on recent outbreaks of high-mortality coronavirus infections and diseases that disproportionately affect the developing world.
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Project description:The development of a successful vaccine, which should elicit a combination of humoral and cellular responses to control or prevent infections, is the first step in protecting against infectious diseases. A vaccine may protect against bacterial, fungal, parasitic, or viral infections in animal models, but to be effective in humans there are some issues that should be considered, such as the adjuvant, the route of vaccination, and the antigen-carrier system. While almost all licensed vaccines are injected such that inoculation is by far the most commonly used method, injection has several potential disadvantages, including pain, cross contamination, needlestick injury, under- or overdosing, and increased cost. It is also problematic for patients from rural areas of developing countries, who must travel to a hospital for vaccine administration. Noninvasive immunizations, including oral, intranasal, and transcutaneous administration of vaccines, can reduce or eliminate pain, reduce the cost of vaccinations, and increase their safety. Several preclinical and clinical studies as well as experience with licensed vaccines have demonstrated that noninvasive vaccine immunization activates cellular and humoral immunity, which protect against pathogen infections. Here we review the development of noninvasive immunization with vaccines based on live attenuated virus, recombinant adenovirus, inactivated virus, viral subunits, virus-like particles, DNA, RNA, and antigen expression in rice in preclinical and clinical studies. We predict that noninvasive vaccine administration will be more widely applied in the clinic in the near future.
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