This document discusses lactic acid bacteria (LAB) and their potential use as vaccines. It outlines that LAB naturally colonize mucosal membranes and could serve as ideal mucosal vaccine delivery vehicles. Examples are given of LAB like Lactococcus lactis being genetically engineered to express antigens from pathogens like Brucella abortis and Helicobacter pylori. The benefits of LAB vaccines are their safety, ability to survive the stomach, and lack of endotoxicity. Future work aims to develop multi-valent LAB vaccine vectors in clinical trials with biological containment to ensure environmental safety.

1. SHRIKANT YANKANCHI
Ph.D SCHOLAR
IABT, UAS DHARWAD

2. Contents...
• Mucosal membrane
• Vaccines
• Lactic acid bacteria (LAB)
• Potential biomedical LAB applications
• LAB as Vaccines
• Steps of medical translation of live L. lactis-based
vaccines
• Benefits of LAB based Vaccines
• Future perspectives

3. Mucosal membrane
• Mucosal membrane-Lines various cavities in the
body
• Prevents the entry of pathogens, dust particles
• 1st line of defence against mucosal infection

4. How it acts on pathogens?
Physiological
/non-specific
Immunological
mechanism
Mucous layer
Acidic/ enzymatic
microflora
Producing antibodies (IgA)

5. Vaccines
Vaccines have historically been the most effective means
to fight and eradicate infectious diseases
A vaccine is a biological preparation that provides
active acquired immunity to a particular disease
vaccine typically contains
An agent that resembles disease-causing microorganism
and is often made from weakened or killed forms of the
microbe, its toxins or one of its surface proteins.

6. Bacterial vaccines
Contain killed or attenuated bacteria that activate the
immune system
Antibodies are built against that particular bacteria,
and prevents bacterial infection later
An example of a bacterial vaccine is the
Tuberculosis vaccine

7. • Typhoid vaccine (Ty21a) contains live attenuated
Salmonella typhi - administered orally either as a
liquid or as acid resistant capsules
• live bacteria is against cholera and is given orally
as a single dose of attenuated Vibrio cholerae
(CVD 103-HgR) in liquid formulation
• Vaccines can be delivered by – injection or
mucosal delivery

8. According to Jennings et al. (1998), an ideal
mucosal vaccine should
a) promote an effective contact of the antigen
with the immune system;
b) stimulate specific humoral and cell-mediated
immunity responses;
c) elicit a long-lasting protection after a single-
dose in early infancy; and
d) be stable and non-toxic

9. Lactic acid bacteria (LAB)
Represent a group of different gram-positive microorganisms,
non sporulating bacteria
This group is distinguished by the ability to carry out
fermentation of carbohydrates to form lactic acid
Beneficial role played by these microorganisms in the humans
and other animals
Present in many foods and are frequently used as probiotics
to improve some biological functions in the host
Perdigón et al. 2001

10. Lactic Acid Bacteria (LAB) or Lactics
plants, meat, and dairy
Dairy products - acidophilus milk, yogurt,
buttermilk, and cheeses
The Lactics are also important commercially in
the processing of meats (sausage, cured hams),
alcoholic beverages (beer, fortified spirits), and
vegetables (pickles, and saukerkraut).

11. Potential biomedical LAB applications
LAB as adjuvants,
immunostimulators, or
Therapeutic drug delivery systems
Factories to produce therapeutic molecules

12. Why we choose LAB as vaccines?
• Lactobacillus genus, are able to colonise cavities such as the
mouth, the urogenital or the gastrointestinal tracts, where
they play a critical role in maintaining a balanced normal
micro flora
• Preventing or lowering the incidence or recurrent urinary or
digestive tract infections
• LAB are quite acid resistant and certain strains are able to
effectively survive passage through the stomach
• Absence of LPS in their cell wall virtually eliminates the risk of
endotoxic shock

13. Important genera of (LAB)
 Lactococcus, Lactobacillus, Leuconostoc, Streptococcus
and Pediococcus.
Therapeutically used species
 L. acidophilus , L. brevis, L. casei, L. bulgaricus and L.
bifidus.

14. • Live vaccine or vaccine delivery vehicle
• The evolution of genetic engineering
techniques
• Expressing heterologous proteins in different
cellular compartments
• improving their antigenic potential for the
production of vaccines against viruses,
bacteria, and parasites.
Exploitation of LAB

15. LAB as vaccine delivery vehicle
• The use of bacteria as vaccine delivery vehicles implies
construction of recombinant strains that contain the gene
cassette encoding the antigen
• Several genera of LAB are being tested as vaccine delivery
vehicles
Vaccines deliver vehicle
 Expresses an antigen from another species
 The vaccine component to be delivered can be either protein or
DNA
 Use of live viral or bacterial vectors for the production of
replicative particulate antigens in vivo

16. LAB as vaccine vehicles
Mohammed Bahey-El-Din, 2012

17. LAB as live vaccine
As Live bacterial vaccines
 Designed to induce an immune response Itself
 To develop LAB as live vaccines, they have to be
genetically transformed
Mohammed Bahey-El-Din, 2012

18. Steps of medical translation of live L. lactis-based vaccines
Mohammed Bahey-El-Din, 2012

19. • Lactococcus lactis - Brucella abortis and Helicobacter pylori
• Streptococcus gordonii prototype vaccines against HIV and
measles
• With Lactobacillus, prototype vaccines against anthrax and
rotavirus are under development, and have already been
obtained against tetanus
Recent developments

20. Benefits of LAB based Vaccines
Eg: Lactococcus lactis
Lactococcus lactis is a GRAS (generally regarded
as safe) bacterium that is widely used in the food
industry
Intensive genetic and molecular research -
potential new biomedical applications
– vaccine delivery,
– gene delivery,
– heterologous protein expression and
– therapeutic drug delivery

21. Future perspectives
• No or few lactococcal vaccine candidates are
currently under clinical investigation
• The use of biological containment strategies may be
necessary to prevent survival of genetically modified
vaccine strains in the environment
• The ultimate aim will be to develop environmentally
safe, multi-valent LAB vaccine vectors against a
variety of different pathogens

22. Thank you
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