Delivery strategies to enhance mucosal vaccination (original) (raw)
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Delivery systems: a vaccine strategy for overcoming mucosal tolerance?
Expert Review of Vaccines, 2009
Antigens administered via the oral and, to a lesser extent, the nasal route are potentially able to invoke tolerance, resulting in a nonreactive immune response. This has been a hurdle for mucosal vaccine development and yet the desire to induce protective local and systemic responses, with pain-free and more convenient products, has been the impetus driving mucosal vaccine R&D. Nevertheless, few mucosal vaccines have reached the marketplace and products are still treated with caution, particularly where live organisms are utilized. In this review, we examine the use of delivery systems with adjuvant properties as key components in a vaccine strategy that does not require the use of live vectors to overcome tolerance and have exemplified their success in mucosal vaccines, concentrating on the nasal and oral routes of administration.
Mucosal immunization: A realistic alternative
Human Vaccines, 2010
Most infections occur at or through mucosal surfaces. Despite this knowledge, current vaccination practices rely predominantly on parenteral administration with only a few vaccines being registered for administration by the mucosal route. while mucosal immunization brings many advantages, the lack of reliable delivery systems has been a major drawback to date. with the recent advances in delivery system technology and the improved understanding of site specific mucosal immune mechanisms, mucosal immunization offers an exciting alternative vaccination strategy.
Strategies for intranasal delivery of vaccines
Drug Delivery and Translational Research, 2012
The vast majority of human pathogens colonize and invade at the mucosal surfaces. Preventing infection at these sites via mucosally active vaccines is a promising and rational approach for vaccine development. However, it is only recently that the stimulation of local immunity at the mucosal surfaces has become a primary objective in addition to inducing systemic immunity. This review describes vaccine formulations designed for mucosal delivery to the nasal-associated lymphoid tissue, via intranasal administration. The association of antigens with mucosal adjuvants and delivery systems is emphasised.
Polymers
Most currently available commercial vaccines are delivered by systemic injection. However, needle-free oral vaccine delivery is currently of great interest for several reasons, including the ability to elicit mucosal immune responses, ease of administration, and the relatively improved safety. This review summarizes the biological basis, various physiological and immunological barriers, current delivery systems with delivery criteria, and suggestions for strategies to enhance the delivery of oral vaccines. In oral vaccine delivery, basic requirements are the protection of antigens from the GI environment, targeting of M cells and activation of the innate immune response. Approaches to address these requirements aim to provide new vaccines and delivery systems that mimic the pathogen’s properties, which are capable of eliciting a protective mucosal immune response and a systemic immune response and that make an impact on current oral vaccine development.
Mucosal adjuvants and delivery systems for protein-, DNA and RNA-based vaccines
Immunology and Cell Biology, 2004
Almost all vaccinations today are delivered through parenteral routes. Mucosal vaccination offers several benefits over parenteral routes of vaccination, including ease of administration, the possibility of self-administration, elimination of the chance of injection with infected needles, and induction of mucosal as well as systemic immunity. However, mucosal vaccines have to overcome several formidable barriers in the form of significant dilution and dispersion; competition with a myriad of various live replicating bacteria, viruses, inert food and dust particles; enzymatic degradation; and low pH before reaching the target immune cells. It has long been known that vaccination through mucosal membranes requires potent adjuvants to enhance immunogenicity, as well as delivery systems to decrease the rate of dilution and degradation and to target the vaccine to the site of immune function. This review is a summary of current approaches to mucosal vaccination, and it primarily focuses on adjuvants as immunopotentiators and vaccine delivery systems for mucosal vaccines based on protein, DNA or RNA. In this context, we define adjuvants as protein or oligonucleotides with immunopotentiating properties co-administered with pathogenderived antigens, and vaccine delivery systems as chemical formulations that are more inert and have less immunomodulatory effects than adjuvants, and that protect and deliver the vaccine through the site of administration. Although vaccines can be quite diverse in their composition, including inactivated virus, virus-like particles and inactivated bacteria (which are inert), protein-like vaccines, and non-replicating viral vectors such as poxvirus and adenovirus (which can serve as DNA delivery systems), this review will focus primarily on recombinant protein antigens, plasmid DNA, and alphavirus-based replicon RNA vaccines and delivery systems. This review is not an exhaustive list of all available protein, DNA and RNA vaccines, with related adjuvants and delivery systems, but rather is an attempt to highlight many of the currently available approaches in immunopotentiation of mucosal vaccines.
Mucosal vaccine delivery: Current state and a pediatric perspective
Most childhood infections occur via the mucosal surfaces, however, parenterally delivered vaccines are unable to induce protective immunity at these surfaces. In contrast, delivery of vaccines via the mucosal routes can allow antigens to interact with the mucosa-associated lymphoid tissue (MALT) to induce both mucosal and systemic immunity. The induced mucosal immunity can neutralize the pathogen on the mucosal surface before it can cause infection. In addition to reinforcing the defense at mucosal surfaces, mucosal vaccination is also expected to be needle-free, which can eliminate pain and the fear of vaccination. Thus, mucosal vaccination is highly appealing , especially for the pediatric population. However, vaccine delivery across mucosal surfaces is challenging because of the different barriers that naturally exist at the various mucosal surfaces to keep the pathogens out. There have been significant developments in delivery systems for mucosal vaccination. In this review we provide an introduction to the MALT, highlight barriers to vaccine delivery at different mucosal surfaces, discuss different approaches that have been investigated for vaccine delivery across mucosal surfaces, and conclude with an assessment of perspectives for mucosal vaccination in the context of the pediatric population.
Mucosal Delivery of Vaccine by M Cell Targeting Strategies
Current Drug Therapy, 2014
Mucosal vaccination is one of the most effective methods to prevent infectious diseases because most pathogens enter the body at mucosal surfaces. Mucosal vaccination induces not only systemic immune responses but also mucosal responses compared to parenteral vaccination that induces poor mucosal immunity. Another advantages of using mucosal vaccines are high patient compliance, low cost and easy other administration. Despite these advantages, very few mucosal vaccines are commercially available today. This is because mucosal vaccines are prone to degradation in the harsh conditions of the gastrointestinal (GI) tract lowering the bioavailability of antigens to induce immune responses. Therefore, protective and effective formulations are required for successful mucosal vaccination. Accordingly, the use of nano-and micro-polymeric particles has received much attention as delivery vehicles of antigens because they can protect the antigens from degradation in the GI tract and they also enhance the antigen uptake in mucosal-associated lymphoid tissue. Particularly, mucoadhesive polymeric carriers are the most promising vehicles for mucosal vaccine delivery because these carriers retain the vaccines on the mucosal tissues for longer period thus improving the bioavailability of the antigens. Most importantly, M cells on the follicle-associated epithelium of the Peyer's patch play a key role in mucosal infection and immunity because they uptake and deliver antigens across mucosal epithelia to the lymphoid tissues via transcytosis. In this review, we dig the role and characteristics of M cells on mucosal immunization and explore the molecules of M cells for targeted delivery of antigens by polymeric particle system.
New Insights in Mucosal Vaccine Development
Vaccine
Mucosal surfaces are the major entrance for infectious pathogens and therefore mucosal immune responses serve as a first line of defence. Most current immunization procedures are obtained by parenteral injection and only few vaccines are administered by mucosal route, because of its low efficiency. However, targeting of mucosal compartments to induce protective immunity at both mucosal sites and systemic level represents a great challenge. Major efforts are made to develop new mucosal candidate vaccines by selecting appropriate antigens with high immunogenicity, designing new mucosal routes of administration and selecting immune-stimulatory adjuvant molecules. The aim of mucosal vaccines is to induce broad potent protective immunity by specific neutralizing antibodies at mucosal surfaces and by induction of cellular immunity. Moreover, an efficient mucosal vaccine would make immunization procedures easier and be better suited for mass administration. This review focuses on contemporary developments of mucosal vaccination approaches using different routes of administration.► To date, mucosal vaccines are poorly efficient. ► Select antigens, adjuvant and design new mucosal routes of administration. ► Induce protective immunity at mucosal surfaces. ► Mucosal vaccine would make immunization procedures easier for mass administration.