LACTIC ACID BACTERIA AS VACCINES

SHRIKANT YANKANCHIPh.D SCHOLAR

IABT, UAS DHARWAD

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

Mucosal membrane

• Mucosal membrane-Lines various cavities in the

body

• Prevents the entry of pathogens, dust particles

• 1st line of defence against mucosal infection

How it acts on pathogens?

Physiological/non-specific

Immunological mechanism

Mucous layerAcidic/ enzymatic

microfloraProducing antibodies (IgA)

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.

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

• 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

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

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

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).

Potential biomedical LAB applications

LAB as adjuvants,

immunostimulators, or

Therapeutic drug delivery systems

Factories to produce therapeutic molecules

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

Lactic Acid bacteria (LAB)Important genera of (LAB) Lactococcus, Lactobacillus, Leuconostoc, Streptococcus

and Pediococcus. Therapeutically used species L. acidophilus , L. brevis, L. casei, L. bulgaricus and L.

bifidus.

• 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

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

LAB as vaccine vehicles

Mohammed Bahey-El-Din, 2012

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

Steps of medical translation of live L. lactis-based vaccines

Mohammed Bahey-El-Din, 2012

• 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

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

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

Thank you

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