Strategies for intranasal delivery of vaccines (original) (raw)
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Delivery strategies to enhance mucosal vaccination
Expert Opinion on Biological Therapy, 2009
Background: Vaccines capable of eliciting cellular and humoral immune responses in tandem could provide prophylactic and therapeutic responses against infectious diseases and cancer. These responses can be induced systemically and at mucosal surfaces by activating the mucosal immune system, but rarely successfully due to challenges associated with mucosal delivery. Objective: To investigate delivery strategies to improve the effectiveness of mucosal vaccines. Methods: Different challenges are associated with different types of vaccines. We consider administration routes, schedules, carrier systems and adjuvants that can be used to overcome these challenges to enhance mucosal vaccination. Results/conclusions: The use of particle-mediated delivery systems is an effective strategy to enhance mucosal vaccination by protecting immunogenic material during delivery, providing targeted delivery systems, and allowing incorporation of adjuvant material.
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.
Scandinavian Journal of Immunology, 2006
Sixty-five healthy adult volunteers were immunized four times at 1-week intervals with an inactivated whole-virus influenza vaccine based on the strain A/New Caledonia/20/99 (H1N1) without adjuvant. The vaccine was administered as nasal spray with a newly developed device to secure intranasal delivery (OptiMist TM , OptiNose AS, Oslo, Norway), as regular nasal spray, nasal drops or as an oral spray. Significant IgA-antibody responses in nasal secretions were induced in volunteers immunized intranasally but not after oral spray immunization. In saliva, IgA antibodies were only marginally amplified even after oral spray immunizations. At least 73% of the volunteers belonging to any group of vaccine delivery reached serum haemagglutination inhibition titres of 40 or higher, considered protective against influenza, after only two vaccine doses. Those who had the vaccine delivered intranasally also showed evidence from in vitro secretion of granzyme B that cytotoxic T cells had been stimulated. Although immunization with the breath-actuated OptiMist TM device and nasal drops were superior with respect to both mucosal and systemic immune responses, oral spray immunization might still be considered for studies of mucosal adjuvants that are not yet acceptable for intranasal use.
Development and use of mucosal vaccines: Potential and limitations
2021
Mucosal surfaces represent a major gateway to microorganisms which may be harmful to health. The humoral immune response has an important action in the defense of these surfaces, as it is able to prevent the entry of pathogens in the body. Vaccines with local application have been evaluated in order to stimulate an efficient immune response in the mucous membranes, since conventional vaccines, for parenteral application, tend to stimulate a mostly systemic response. Vaccines that use the mucosa as an inoculation route are able to generate an immune response directly in the application mucosa and corresponding mucosa, since the mucosal system is integrated, which represents an important advantage in choosing the inoculation route. This paper aims to illustrate some concepts related to mucosal immunity in general, as well as to gather information about what has been studied in relation to mucosal routes of administration of vaccines, immunomodulators and antigen delivery systems.
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.
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.
Manipulating systemic and mucosal immune responses with skin-deliverable adjuvants
Journal of Biotechnology, 1996
Most medically important bacterial and viral pathogens gain entry into the body either via the skin or a mucosal surface. Vaccination provides a viable and cost-effective strategy for the prevention of such diseases and it has always been a principal aim with vaccinologists, to be. able to promote simultaneously, protective immune responses both systemically and at mucosal surfaces. The paradigm that mucosal immunity is best stimulated by exposure to antigen via a mucosal route simply because inductive sites such as Peyer's patches and bronchial associated lymphoid tissues are located in the mucosal epithelium, has promoted a plethora of immunizing strategies aimed at delivering both antigen and adjuvant to mucosal surfaces. We have developed a novel adjuvant system capable of intradermal delivery of antigens complexed in an ISCOSOME delivery vehicle. This adjuvant, referred to as a skin and mucosal adjuvant or SAMA4, was efficacious in eliciting both systemic and mucosal IgG and IgA antibodies in sheep, pigs and mice. SAMA does not induce granulomatous lesions at the site of vaccine delivery and can be used to deliver adjuvanted antigens by other routes including intranasal, oral and intravaginal. Using ovalbumin as a test antigen, intradermally delivered ovalbumin-SAMA complexes was found to be very effective in promoting a cytotoxic T cell response. Attempts to dissect the mode of action of SAMA by flow cytometric analysis of lymphocyte populations from the spleen, lung, liver and thymus revealed an effect of route of vaccine delivery upon the composition of specific lymphocyte subsets in these various organ compartments. From this, it can be inferred that SAMA induced a route-dependent re-mobilization and alteration in lymphocyte trafficking patterns. Other mucosal adjuvants such as cholera toxin B and microspheres, when injected intradermally, tended to promote primarily, an IgG and not an IgA response against the carrier antigen.