ABSTRACT
Mucus is a viscoelastic gel that acts as a protective barrier for epithelial surfaces. The mucosal vehicles and adjuvants need to pass through the mucus layer to make drugs and vaccine delivery by mucosal routes possible. The mucoadhesion of polymer particle adjuvants significantly increases the contact time between vaccine formulations and the mucosa; then, the particles can penetrate the mucus layer and epithelium to reach mucosa-associated lymphoid tissues. This review presents the key findings that have aided in understanding mucoadhesion and mucopenetration while exploring the influence of physicochemical characteristics on mucus-polymer interactions. We describe polymer-based particles designed with mucoadhesive or mucopenetrating properties and discuss the impact of mucoadhesive polymers on local and systemic immune responses after mucosal immunization. In future research, more attention paid to the design and development of mucosal adjuvants could lead to more effective vaccines.
ABSTRACT
There is now strong evidence to support the interest in using lactic acid bacteria (LAB)in particular, strains of lactococci and lactobacilli, as well as bifidobacteria, for the development of new live vectors for human and animal health purposes. LAB are Gram-positive bacteria that have been used for millennia in the production of fermented foods. In addition, numerous studies have shown that genetically modified LAB and bifodobacteria can induce a systemic and mucosal immune response against certain antigens when administered mucosally. They are therefore good candidates for the development of new mucosal delivery strategies and are attractive alternatives to vaccines based on attenuated pathogenic bacteria whose use presents health risks. This article reviews the most recent research and advances in the use of LAB and bifidobacteria as live delivery vectors for human and animal health.
Subject(s)
Gastrointestinal Microbiome , Lactobacillales , Vaccines , Animals , Bifidobacterium/genetics , Genetic Vectors/genetics , Humans , Lactobacillales/geneticsABSTRACT
Introduction: The development of more efficacious vaccines, especially subunit vaccines administered via non-invasive routes, is a priority in vaccinology. Nanogels are materials that can meet the requirements to serve as efficient vaccine delivery vehicles (in terms of thermo-sensitivity, biocompatibility, and pH-responsiveness; among others); thus there is a growing interest in exploring the potential of nanogels for vaccine development. Areas covered: Herein, a critical analysis of nanogel synthesis methodologies is presented and nanogel-based vaccines under development are summarized and placed in perspective. Promising vaccine candidates based on nanogels have been reported for cancer, obesity, and infectious diseases (mainly respiratory diseases). Some of the candidates were administered by mucosal routes which are highly attractive in terms of simple administration and induction of protective responses at both mucosal and systemic levels. Expert opinion: The most advanced models of nanogel-based vaccines comprise candidates against cancer, based on cholesteryl pullulan nanogels evaluated in clinical trials with promising findings; as well as some vaccines against respiratory pathogens tested in mice thus far. Nonetheless, the challenge for this field is advancing in clinical trials and proving the protective potential in test animals for many other candidates. Implementing green synthesis approaches for nanogels is also required.
Subject(s)
Drug Delivery Systems/methods , Nanogels/chemistry , Nanoparticles/chemistry , Vaccines/immunology , Animals , Drug Carriers , Drug Development , Glucans , Humans , Mice , NeoplasmsABSTRACT
Mucosal vaccination offers attractive advantages to conventional systemic vaccination. Most pathogens enter or establish infection at mucosal surfaces. This represents an enormous challenge for vaccine development. Nevertheless, the availability of safe and effective adjuvants that function mucosally is the major limitation. Therefore, we investigated the impact of mucosal immunization with the Neisseria meningitidis B proteoliposome (AFPL1, Adjuvant Finlay Proteoliposome 1) and its-derived cochleate (Co, AFCo1). They contain multiple PAMPs as immunopotentiators and have delivery system ability as well as Th1 polarization activity. Groups of female mice were immunized by nasal, oral, intravaginal, or intramuscular routes with three doses with AFPL1/AFCo1 alone or containing ovalbumin or glycoprotein (g) D2 from Herpes Simplex Virus type 2 (HSV-2). High levels of specific IgG antibodies were detected in sera of mice vaccinated with either route. However, specific IgA antibodies were produced in saliva and vaginal wash only following mucosal delivering. The polarization to a Th1 pattern was confirmed by testing the induction of IgG2a/IgG2c antibody, positive delayed-type hypersensitivity reactions, and gIFN production. Additionally, AFCo1gD2 showed practically no vaginal HSV-2 replication and 100 percent protection against lethal vaginal HSV-2 challenge. In conclusion, the results support the use of AFCo1 as potent Th1 adjuvant for mucosal vaccines, particularly for nasal route(AU)