periodontal vaccines and their availability,uses

1. T.HUDSON JONATHAN
II ND YR MDS

2. Contents
 Introduction
 Basics Of Vaccination
 History of periodontal
vaccines
 Indications
 Porphyromonas
gingivalis as a target
 A.actinomycetemcomita
ns as a target
 Mechanism of Action
 Active Immunization
 Passive Immunization
 Genetic immunization
 Advantages
 Limitations
 Future research
 Conclusion
 References

3. Introduction
 Periodontitis is defined as ‘an inflammatory disease of the
supporting tissues of teeth caused by specific
microorganisms or group of microorganisms resulting in
progressive destruction of the periodontal ligament and
alveolar bone with pocket formation, recession or both .
Caranzza’s clinical Periodontology, 10th (Edn.)

4.  Current concept of etiopathogenesis include:
1. Host associated factors,
2. Genetic predisposition,
3. Immune system dysfunction and
4. Environmental factors, such as the presence of virulent
periodontal pathogens (bacteria or viruses) in the form
of dental biofilm.

5.  So to arrest or prevent the progression of periodontal
disease it will include combination approaches
 Periodontal pathogens associated with periodontitis
predominantly are gram-negative, anaerobic bacteria
namely P. gingivalis, A. actinomycetemcomitans T.
denticola and T. forsythus etc. Happy et al 2013
host immune
modulation
pathogen-specific
approaches

6.  Recent advances in cellular and molecular biology have
led to the development of new strategies for vaccines
against many types of infectious diseases.
 It has long been recognized that individuals who
recovered from a disease developed subsequent
resistance to the same. Kudyar, et al 2011

7.  Thus, various immunization approaches both as active
and passive immunization, against periodontal
pathogens have been explored either using the whole
organism or specific virulence factors.

8. Basics Of Vaccination
 Vaccine is a material that induces an immunologically
mediated resistance to a disease . Vaccines are generally
composed of killed or attenuated organism or subunits of
organism or DNA encoding antigenic proteins of
pathogens. Thomas et al 2015

9.  Vaccination is the development of immunity or
resistance to infection, after a secondary response that is
adequate to consider the individual immune to a
subsequent infection. Kundyar et al 2011
 Louis Pasteur, in 1881- the first vaccine against rabies,
and established the basic paradigm for vaccine
development, ie
isolation inactivation
injection of the
causative
microorganism

10.  Foremost step in vaccine development:
• Identification of an antigenic component from various
organisms that can provide immune protection, and
mostly the target is on the Antigens of infectious
pathogenic bacteria and viruses. Kudyar et al 2011
 Types of vaccination:
I. Active immunization
II. Passive immunization
III. DNA vaccination

11.  Active immunization: Here, an individual immune
system is stimulated by administrating killed or live
attenuated products derived from micro-organisms.

12.  Passive immunization : Here, the antibodies formed in
one individual are transferred to another.

13.  DNA vaccination : Here, DNA plasmids encoding genes
required for antigen production are transferred to an
individual.

14.  Characteristics of an effective vaccine
Safety Protectivity
The ability to provide
sustained protection
The ability to produce
neutralizing antibodies
Stimulation of
protective t-cells.
Pearl Bhardwaj. Periodontal Vaccine-Armour against Periodontitis. J Dental Sci 2019, 4(4):

15. Practical considerations like
• Cost-effectiveness
• Biological stability
• Access
• Minimum contraindications and side effects

16. History of periodontal vaccines
 In the early twentieth century, three periodontal vaccines
were employed :
• Pure cultures of streptococcus and other organisms
• Autogenous vaccines
• Stock vaccines Thomas G, et al 2015
 Examples include Vancott’s vaccine and Inava endocarp
vaccine.

17.  Primary role -to eradicate the global periodontal disease
burden with the ultimate purpose of lowering periodontal
disease associated morbidity in humans.
 The vaccine effect should be seen
Help in
maintaining oral
health
maximize retention
of the natural
dentition
minimizing the need for
prosthetic or implant
restorations
Choi et al 2010

18. Indications
i. Patients with severe periodontal disease with loss of bone
and teeth,
ii. Inflammation and association with oral bacterial infection
below gum line and
iii. In exacerbated diabetes and cardiovascular disease

19. Porphyromonas gingivalis as a target
 P. gingivalis has been implicated as a major periodonto-
pathogen in human periodontitis through variety of survival
strategies enabling it to evade host defence mechanisms.
 Virulence components of the bacterial cell include
cysteine proteases
Fimbriae
capsular polysaccharide
lipopolysaccharide, and
outer membrane vesicles
Sundqvist et al 1993

20.  Gingipains describe cysteine proteases (major
pathogenic part) P. gingivalis and can be grouped into:
 Gingipains R (RgpA and RgpB): cleaves proteins at
arginine residues
 Gingipain K (porphypain 2, Kgp): cleaves proteins at lysine
residue.(Happy et al 2013)
 Both RgpA and Kgp (but not RgpB) have a hemagglutinin
domain that is essential for the adherence to erythrocytes .

21.  While the catalytic domain (in RgpA, RgpB, and Kgp)
plays an important role in the evasion of the host
defense system by degrading immunoglobulins and
complement proteins and by disturbing the functions of
neutrophils.
 The two major colonization factors of P. gingivalis are
coaggregation factor (outer membrane proteins OMPs)
& hemagglutinins. Happy et al 2013

22. A.actinomycetemcomitans as a target
 A. actinomycetemcomitans is considered another important
pathogen in human periodontal disease, especially in the
localized form of aggressive periodontitis.
 Harano et al.1995 prepared an antiserum against a synthetic
fimbrial peptide of A. actinomycetemcomitans and found
that it blocked the adhesion of the organism to saliva-
coated hydroxyapatite beads, to buccal epithelial cells, and
to a fibroblast cell line.

23.  Also, subcutaneous and intranasal immunization of mice with
capsular serotype b-specific polysaccharide antigen of A.
actinomycetemcomitans resulted in a specific antibody that
efficiently opsonized the organism.
 Mice immunized with antisurface associated material from
A. actinomycetemcomitans exhibited a rise in protective
antibody levels acting as an opsonin. Hermlnajeng et al 2001

24. Mechanism of Action
a) Active Immunization
I. Whole bacterial cells
II. Subunit vaccines
III. Synthetic peptides as
antigens
b) Passive Immunization
I. Murine monoclonal
antibodies
II. Plantibodies
c) Genetic Immunization
I. Plasmid vaccines
II. Live, viral vector
vaccines

25. Active Immunization
Whole cells:
 Here, the entire cell with its
components is inoculated into a host to
bring about active immunization.
 Klausen; 1991 have shown that when
rats immunized with P. gingivalis cells
to both whole cells and partially
purified fimbriae
serum
antibodies
collagenase
and cysteine
proteinases

26.  Kesavalu; 1992 observed protection against invasion in mouse
chamber model, but the immune response to whole cells or
selected envelope component did not completely abrogate
lesions, but eliminated mortality.

27. Sub unit vaccines:
 In this type, a part of the bacterial cell is used for
immunization. Either the outer component or the
fimbriae is used.
 Evans; 1992 reported that immunization with highly
purified P. gingivalis fimbrial preparations as well as
whole cells and soluble antigens of P. gingivalis
protected against periodontal destruction induced by P.
gingivalis in gnotobiotic rats.

28.  Bird; 1995 showed that immunization of experimental
animals with an outer membrane preparation isolated
from P. gingivalis induces elevated levels of specific
antibody and provides protection against the progression
of periodontal disease.

29. Synthetic peptides:
 These require synthesis of linear and branched polymers of
3-10 amino acids based on the known sequences of
microbial antigens. Such peptides are weakly
immunogenic by themselves and need to be coupled to
large proteins to induce antibody response.
 Two ways to develop:
• By deduction of the protein sequence of microbial antigens
from RNA sequence data.
• By testing overlapping peptides and by mutational analysis.

30.  Advantages of synthetic peptide are:
• Safe
• Cheap
• Easy to store and handle
• Ideally suited for specific targeting, which is not possible
with classical vaccines.
 Genco; 1992 found that synthetic peptides based on the
protein structure of fimbrillin inhibit the adhesion of Pg
to saliva-coated hydroxyapetite crystals in vitro.

31. Passive Immunization
Murine monoclonal antibodies:
 In this, the antibodies are obtained by inoculating the
antigens into mice. These antigens are then injected into the
host that brings about passive immunization. Gupta et al
1996
 Booth; 1996 developed it for P. gingivalis, that prevented
recolonization of deep pockets by this pathogen in
periodontitis patients.

33. Plantibodies:
 A recent approach for vaccination strategies is molecular
biological techniques to express bacterial or viral antigens in
plants, which could be used as orally administered vaccines
European journal of plant pathology. 1992;98.

34.  Ma; 2000, characterized a secretory IgG antibody
against Streptococcus mutans produced in transgenic
plants.
 Advantages:
• Higher stability
• Higher degree of functionality and
• Protection against colonization by S mutans.

35. Genetic immunization
 The strategy of Genetic immunization involves genetic
engineering or recombinant DNA technology.(early 1990’s)
 There are two types:
• Plasmid vaccines
• Live, viral vector vaccines

36. Plasmid vaccines:
 DNA does not have the ability to grow, whereas
plasmids have the ability to grow.
 Disadvantages - in some cases it may lead to
oncogenesis.
Plasmids
DNA of a
particular
pathogen
antibodies Immunization
(host)
(Fused &
inoculated in
animal)

38. Live, viral vector vaccines:
 A variety of infectious but nondisease causing DNA or
RNA viruses or bacteria have been engineered to
express the proteins of a disease-producing organism.
 The vector enters the body cells where the proteins are
generated and then induce humoral or cellular immune
responses. Barry et al 1997

39.  Methods of DNA vaccine administration
• Intranasal
• Intramuscular
• Gene gun
 Advantages of DNA vaccines
• The ease of manufacture
• Stable by nature
• Simple

40. Advantages
1. Current management options inadequate for many
2. Current disease prevention options inadequate for most
3. Nonexistence of equivalent technology for periodontal
disease control or prevention.

41. Limitations
 Multi factorial and complex nature of periodontal disease.
 Maintaning adequate antibody levels for longer periods.
 Vaccine contamination.
 To stimulate helper T-cell polarization that exerts cytokine
functions optimal for protection against bacteria and tissue
destruction.
 Toxic reactions to inactivated whole vaccines.
Kudyar et al 2011.Periodontal Vaccine:A dream or reality, Journal of Indian Society
of Periodontology 15: 115-120.

42.  Numerous invitro studies and those undertaken in
animal models have proved beyond doubt the efficacy of
these vaccines.
 Translation of similar results in humans and their
subsequent application in clinical scenarios is the
daunting next step in the field of periodontal
vaccination.
Future research

43.  The new approach of the genomic era, to develop
vaccines starting from the genomic information rather
than growing the causative microorganism has expanded
in order to include multi-representatives of the same
species.
 And this pan-genome approach has shown tremendous
potential for making vaccines that once might have been
impossible to design.

44. Conclusion
 The current treatment of periodontitis is nonspecific and is
centered on the removal of subgingival plaque by
mechanical debridement.
 And it is costly, painful and has variable prognosis, in part
due to poor compliance of the patients.

45.  So the development of multispecies vaccine that is able
to target all four prime bacterial species, which have
been implicated in the development of periodontitis,
may be more successful than a vaccine against a single
species.

46. References:
 Kudyar, et al.: Periodontal vaccine, Journal of Indian
Society of Periodontology - Vol 15, Issue 2, Apr-Jun
2011.
 Kaur Rk: Periodontal Vaccine: A New Horizon , Int J
Dent Med Res ; Nov - Dec 2014 ,Vol 1 ,Issue 4
 Pearl Bhardwaj. Periodontal Vaccine-Armour against
Periodontitis. J Dental Sci 2019, 4(4):

47.  Daisy H et al ;Periodontal Vaccines , Journal of Dental
& Allied Sciences 2013;2(1)21-23
 Gupta And Deepa: Periodontal Vaccines-new Vista,
2016 ;Journal Of Current Research In Scientific
Medicine.

48. Thank you