1. The document discusses mucosal vaccine delivery systems, including their advantages over injectable vaccines. It describes various mucosal delivery methods like emulsion-type, liposome-based, polymeric nanoparticles, virosomes, and melt-in-mouth strips.
2. It summarizes a case study on the preparation of alginate-coated chitosan microparticles for vaccine delivery and their ability to modulate antigen release and protect from degradation.
3. Overall, the document outlines the promise of mucosal vaccines for improved compliance and induction of mucosal immunity, but also challenges like rapid clearance that must be addressed through innovative delivery systems and adjuvants.
2. INTRODUCTION
Vaccination against infectious diseases has proven to be an asset
in preventing diseases and has contributed significantly to an
increase in life expectancy. [1]
It is believed that the first productive interaction among the most
infectious agents and that host is with mucosal surfaces, especially
the agents and the host is with mucosal surfaces, especially the
nasal, oropharyngeal, respiratory, genitourinary and
gastrointestinal mucosa. [2]
2
4. MUCOSAL DELIVERY OF VACCINES
Mucosal surfaces area is major portal of entry for many human
pathogens that are the cause of infectious diseases
worldwide.[3]
Immunization by mucosal routes may be more effective at
inducing protective immunity against mucosal pathogens at
their sites of entry.[4]
Efforts have focused on efficient delivery of vaccines antigens to
mucosal sites that facilitate uptake by local antigen-presenting
cells to generate protective mucosal immune responses. [5] 4
6. MUCOSAL TYPE
The adult human mucosa lines the surfaces of the digestive,
respiratory and genitourinary tracts, covering an immune
surface area that is nearly 200 times greater than that of the
skin. It is estimated that 70% of the infectious agents enter
the host by mucosal routes.
Mucosal surfaces are typically categorized as type-I and
type-II mucosa.
Type-I mucosa includes surface area of lungs and gut.[6]
6
7. Type-II mucosa include surface area of mouth, esophagus and
cornea.
The female genital tract has both type-I and type-II mucosa.
Most mucosal sites have organized lymphoid follicles, such as
NALT, and GALT, which have assembly of scattered antigen-
reactive cells of immune system, such as B cells, T cells, and
professional antigen presenting cells such as dendritic cells(APCs).
It is widely accepted that mucosal vaccination can induce immune
responses at both systemic and mucosal sites and, prevent the
invasion and colonization of pathogens at mucosal surfaces.[7] 7
CONTINUE……
8. LIMITATION OF INJECTIBLE
VACCINES.
High production cost
Low/poor compliance
Fear of needle borne infection
Lack of mucosal immune response
Injection site pain
Local side effects
8
9. CONTRIBUTION OF POLYMERS IN
MUCOSAL VDS.
The concept of polymeric carrier system(s) offers advantage of
delivering drugs/antigens to a specific target site, where it has
to be released from the carrier.
Polymeric nanoparticles/microparticles can enhance the
immune response to mucosal administered antigens by several
means. [8]
9
10. DESIGN AND STRATEGIES FOR
MUCOSAL DELIVERY
DESIGN AND
STRATEGIES FOR
MUCOSAL DELIVERY
EMULSION TYPE
DELIVERY
LIPOSOME BASED
DELIVERY
POLYMERIC NANO
PARICLES
VIROSOMES
MELT IN MOUTH
STRIPS
10
11. EMULSION TYPE DELIVERY
Emulsions are heterogeneous liquid systems may be w/o or o/w.
Antigens are dissolved in a water phase and emulsified in the oil
in the presence of an appropriate emulsifier.
The controlled release characteristics of an emulsion are
determined by factors such as – Viscosity of oil phase – Oil to
water phase ratio – Emulsion droplet size. [9]
11
12. ADVANTAGES AND DISADVANTAGES
ADVANATGES
Slow release of antigen
DISADVANTAGES
Fever
Sore arm at injection site
Access immunogenic response
12
13. LIPOSOME BASED DELIVERY
Liposomes are spherical shape vesicles containing an
aqueous core which is enclosed by a lipid bilayer.
They are most often composed of phospholipids, especially
phosphatidylcholine, but may also include other lipids, like
Ethanolamine.
13
14. ADVANTAGES AND DISADVANTAGES
ADVANATGES
Easy surface modification
Synthesized from non toxic material
Wide range of antigen encapsulation
plasticity
DISADVANTAGES
Stability problem
Low antigen loading
14
15. POLYMERIC NANO PARTICLES
Polymeric nano particles are submicron-sized colloidal
particles.
Polymeric nanoparticles because of their size are
preferentially taken up by the mucosa associated lymphoid
Tissue.
Limited doses of antigen are sufficient to induce effective
immunization.
Hence, the use of nanoparticles for oral delivery of antigens
is suitable because of their ability to release proteins and to
15
16. VIROSOMES
A Virosome is a a drug or vacine delivery mechanism consisting of
uniflagellar phospholipid membrane vesicle incorporating virus
derived proteins to allow the virosomes to fuse with target cells.
These proteins enable the virosome membranes to fuse with cells
of the immune system and thus deliver the specific antigens
directly to their target cells.
They elicit a specific immune response even with weak
immunogenic antigens.
16
17. Once they have delivered the antigens, the virosomes are
completely degraded within the cells.
17
CONTINUE……
19. MELT IN MOUTH STRIPS
Quick dissolving films containing immunogens.
Melts into liquid that children and infants will swallow easily.
These strips stick and dissolves on the tongue in less than a
minute. (useful for newborns who sometimes spit out the liquid)
EXAMPLE: ROTAVIRUS is a common cause of severe diarrhea
and vomiting in children. ROTAVIRUS VACCINE at present is
available in a liquid or freeze-dried form that must be chilled for
transport and storage, making it very expensive for use in
impoverished areas. 19
21. CHALLENGES FOR MUCOSAL DSS
Presence of Physical/ Epithelial Barriers.
Enzymatic Degradation.
Low Permeability.
Wekness the Antigenicity.
Loss of Bioactivity’
Dilution of Antigens by mucosal Secrecion.
21
22. ADVANTAGES OF MUCOSAL
VACCINE DRUG DELIVERY SYSTEMS.
Induce Primary stage immunity.
Possible mass vaccination.
Systematic- mucosal response.
Needle free.
Non- invase.
22
26. 26
PROSPECTS FOR MUCOSAL VACCINE:
shutting the door on SARS-CoV-2.
AIM :-
This Articles summarizes the approaches to an effective mucosal vaccine formulation which can be a
recording approaches to combat the unprecedently the react posed by this emerging global pandemic.
OBJECTIVE :-
This PPT summarizes the approaches to an effective mucosal vaccine formulation which can be a
rewarding approach to combat the unprecedented threat posed by this emerging global pandemic.
REFERENCE :-
Hum Vaccine Immunother. 2020 : 1-11. Published online 2020 Sep 15.
doi 101080/21645515.2020.1805992
PMCID: PMC7544966
PMID: 32931361
Rajat Mudgal, Sanetkumar Nehul, and Shaily Tomer.
27. 27
METHOD :-
Design strategies for mucosal vaccine against SARS- COV
• Mucosal Immune System.
• Mucosal Vaccine Platform.
• Antigen Selection.
• Mucosal Adjuvants
• Immunotolearance.
• Immunosenescence.
• Correlates of Protection and testing in animal models.
• Parental vaccines against mucosal pathogens.
• Rapid licensure and production of a mucosal vaccine.
RESULT :-
• global surveillance and vigilance in the post-pandemic scenario should be practiced to help the
world counter a second wave of COVID-19 or other possible future coronavirus outbreaks.
• Mucosal vaccines offer better patient compliance in terms of the physical and psychological
comfort due to absence of needlestick injury and thus are highly compatible for mass
immunization in a pandemic scenario.
28. 28
The current COVID-19 pandemic has virtually brought most world economies to a halt and severely
impacted the lives of a large proportion of the world population. Development of a viable SARS-
CoV vaccine is imperative to reduce mortality and morbidity associated with this novel virus
outbreak.
Vaccine administration using injection involves the cost of injection device, it’s safe disposal, and
the employment of trained medical staff which adds a considerable cost for mass vaccination
especially in developing countries.
The emergence and rapid global spread of SARS-CoV-2 has provided a very small window for basic
and translational studies that propel the development and evaluation of vaccine against a
pathogen. While the knowledge gained from previous studies on SARS-CoV and MERS-CoV can be
used for SARS-CoV-2 vaccine development, it is yet uncertain as to what extent it will work for
SARS-CoV-2 or whether correlates of protection used will faithfully predict protective efficacy.
Potential ADE and waning of vaccine-induced immune response represent other obstacles in the
development of a mucosal vaccine against SARS-CoV-2.
CONCLUSION OF CASE STUDY
30. 30
Preparation of Alginate coated
Chitosan microparticles for vaccine
Delivery.
AIM :-
Preparation of alginate coated chitosan microparticles for vaccine delivery.
OBJECTIVE :-
Absorption of antigens onto chitosan microparticles via electrostatic interaction is a common and
relatively mild process suitable for mucosal vaccine. In order to increase the stability of antigens and
prevent an immediate desorption of antigens from chitosan carriers in gastrointestinal tract, coating onto
BSA loaded chitosan microparticles with sodium alginate was performed by layer-by-layer technology to
meet the requirement of mucosal vaccine.
REFERENCE
1. George M, Abraham TE: Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and
chitosan -a review. J Control Release 2006, 114:1-14
2. Jepson MA, Clark MA, Hirst BH: M cell targeting by lectins: a strategy for mucosal vaccination and drug
delivery. Adv Drug Deliv Rev 2004, 55:511-525.
31. 31
METHOD :-
Loading bovine serum albumin (BSA) to chitosan microparticles :-
Colloid chitosan microparticles were re-dispersed in 25 ml of distilled water at concentration of 5 mg/ml
under continuous ultrasonication (Benchtop 20L, Medisafe, UK Ltd, UK) to disaggregate the chitosan
microparticles. The loading procedure was performed by incubating different concentrations of BSA with
chitosan microparticles under mild agitation at room temperature for 15 min.
Colloid chitosan microparticles were re-dispersed in 25 ml of distilled water at concentration of 5 mg/ml
under continuous ultrasonication (Benchtop 20L, Medisafe, UK Ltd, UK) to disaggregate the chitosan
microparticles. The loading procedure was performed by incubating different concentrations of BSA with
chitosan microparticles under mild agitation at room temperature for 15 min.
Preparation of alginate coated chitosan microparticles :-
BSA loaded chitosan microparticles suspensions with pH value at 5.1 were added dropwisely into sodium
alginate solution (pH = 7.2) at concentration of 10 mg/ml under mild agitation for 10 min. Then the
suspension was centrifuged at 3,400 rpm for 5 min, and the supernatant was discarded. Finally, alginate
coated chitosan microparticles were re-dispersed into calcium chloride (CaCl2) aqueous solution (pH = 7.0)
at concentration of 0.524 mmol/L to crosslink the alginate layer presents on the surface of chitosan
microparticles.
32. 32
RESULT :-
we prepared alginate coated chitosan microparticles by layer-by-layer technology to meet the
requirement of oral administration of antigen for mucosal vaccine. BSA with isoelectric point (PI) of
4.8 was negatively charged when pH>4.8, which could easily absorb cationic chitosan microparticle
at aqueous solution (pH = 7) via electrostatic interaction and was selected as the model protein to
evaluate the properties of alginate coated chitosan microparticles.
Table 1: The size and zeta potential of alginate/BSA/chitosan system :-
Sample
MEAN
PARTICLE SIZE
(nm)
PDI Zeta potential (mV)
lank chitosan microparticles a
BSA-loaded chitosan particles b
Alginate coated BSA loaded chitosan
microparticles c
301.8
404
1324
0.309
0.472
0.450
+45.2
+27.1
-27.8
a chitosan 5 mg/ml, TPP 1 mg/ml.
b chitosan 5 mg/ml, TPP 1 mg/ml, BSA 2 mg/ml.
c chitosan 5 mg/ml, TPP 1 mg/ml, BSA 2 mg/ml, alginate 10 mg/ml
33. 33
In vitrorelease profiles of BSA from uncoated chitosan micropracticles (Black) and coated chitosan
microparticles (Red) in PBS (pH7.4) at 37°C.
34. 34
CONCLUSION OF CASE STUDY
The prepared alginate coated chitosan microparticles, with mean
diameter of about 1 μm, was suitable for oral administration.
Moreover, alginate coating onto surface of chitosan
microparticles could modulate the release behavior of BSA from
alginate coated chitosan microparticles and could effectively
protect model protein (BSA) from degradation against acidic
medium (pH2) in vitro at least for 2 hours.
According to FTIR, some alginate on surface of chitosan
microparticles at 24 h of release test has been dissolved into PBS.
Based on the information demonstrated, the prepared alginate
coated chitosan microparticles might be an effective vehicle for
oral administration of antigens.
35. CONCLUSION
mucosal vaccination has many advantages, a very limited
number of mucosal vaccines have been licensed. The most
widely tested vaccination routes are oral and intranasal.
Future mucosal vaccines should be made with more purified
antigen components, which will require safe and efficacious
adjuvants and delivery systems. Recent developments in
biomaterials and nanotechnology have enabled many innovative
mucosal vaccine trials.
35
36. 36
Future mucosal vaccine carriers, regardless of administration
routes, should share common characteristics. They should
maintain stability in given environments, be mucoadhesive, and
have targeting ability to specific tissues and cells.
CONTINUE……
37. REFERENCES
1. Giteau A, Venier- jullience MC, Aubert-pousered A, Benoit JP, How
to achieve sustained and complete protein release from PLGA –
based microparticles? Int J Pharm 2008,350(1-2):14-26.
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adjuvants; from 1920 to2015 and beyond Vaccines (Basel)
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3. Garcia A, lema D. an updated review of ISCOMSTM and
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4. Jakobsen, H., Bjarnarson, S., Del Giudice, G., Moreau, M., Siegrist,
C.A., and Jonsdottir, I. 2002, Infect. Immun., 70, 1443.
37
38. 5. Agger, E.M., Rosenkrands, I., Olsen, A.W., Hatch, G., Williams, A.,
Kritsch, C., Lingnau, K., von Gabain, A., Andersen, C.S., Korsholm,
K.S., and Andersen, P. 2006, Vaccine, 24, 5452.
6. Illum, l., Farraj, N.F., Fisher, A.N., Gill, L., Miglietta, M., and
Benedetti, L. 1994, J. Controlled Release, 29, 133.
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erratum appears in Nat Biotechnol 1998 May;16(5):478], 153.
CONTINUE……
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