The Production and Delivery of

Edible Plant- and Lactobacteria-derived Vaccines

Dominic Man-Kit Lam

Fung Hon Chu Endowed Chair of Humanics

Hong Kong Baptist University

WHO Meeting at HKBU

24 January 2013

Acknowledgements of Main Collaborators

I. Edible Plants: Prof. Hugh Mason, Prof. Charles Arntzen,

Dr. Jian Jian Shi, Dr. Yee Yee Lam, Dr. Fong Lam

II. Lactobacteria: Dr. Han Lei, Prof. Yuhong Xu

Expression of hepatitis B surface antigen in tomato fruit

Expression of hepatitis B surface antigen in tomato fruit

Genetic manipulation and plant breeding in Corn

can boost expression

Seed generation

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Oral Vaccination for

Swine TGEV With Edible Vaccines Produced in Corn

The First Demonstration Of Vaccination With Edible Vaccines

Advantages of lactic acid bacteria as mucosal-delivery vehicles

1. Lactic acid bacteria are generally regarded as safe (GRAS）, and are extensively used in fermented food products ； 2. Can survive passage through the stomach acid and contact with bile; 3. Fulfill the requirements of a delivery system in mucosal immunization; 4. The mucosal route of administration can potentially stimulate both system and mucosal immune responses, can elicit the production of secretory Ig A; 5. Are taken up to into Peyer’s patches, the inductive sites of the mucosal immune system; 6. Multiple antigens can be expressed in the same strain ； 7. Can be engineered to express targeting antigens and adjuvants;

Wells, J.M. & Mercenier, A. Nature Rev Microbiol 2008, 6(5), 349-362.

Fate of recombinant lactic acid bacteria in the intestinal tract

Wells, J.M. & Mercenier, A. Nature Rev Microbiol 2008, 6(5), 349-362.

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PBS

L.lactis (pNZ8110)

L.lactis (pNZ8150-HA)

L.lactis (pNZ8110-HA)

L.lactis (pNZ8110-pgsA-HA1)

PBS+CTB

L.lactis (pNZ8110)+CTB

L.lactis (pNZ8150-HA)+CTB

L.lactis (pNZ8110-HA)+CTB

L.lactis (pNZ8110-pgsA-HA1)+CTB

H5N1 virus challenge experiment

Immune protection detected by H5N1 virus lethal challenges after oral deliveries of different vaccine preparations

Positive: percent survival＞60%

5 mice/group Lei et al., 2011. Clinical and Vaccine Immunology 18(7): 1046-1051.

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PBS

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capsule-L4

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H5N1 virus challenge experiment

Immune protection against H5N1 virus lethal challenges after oral deliveries of different vaccine preparations

5 mice/group; Positive: percent survival＞60%; Lei et al., 2010. Virology 407 (2): 319-324.

HA

A/duck/Anhui/1/06 (H5N1)

HA

A/Chicken/Shandong/6/96/ (H9N2)

boost H9N2 H5N1(R-1) H5N1 (R-4)

PBS （L1） 2.4±0.54772 2.4±0.47721 2.2±0.44721

H9N2 （L2） 8.2±0.44721 8.0±0.70711 8.2±0.44721

H5N1-M2

（L4）

9.4±0.54721 8.0±0.70711 9.6±0.54772

H5N1-HA

（L6）

9.0±0.70711 9.2±0.83666 9.4±0.54772

1. Much lower costs of production

2. Safety --- no animal-related contaminants, no syringes and

needles used

3. Higher stability (e.g. proteins in seeds can be preserved for years

even at room temp.)

4. Easier compliance, especially for multi-dose vaccinations ---

Vaccines can be kept and administrated orally at home

5. Cost-effective and easier administration of vaccines for animals

(livestock, pets etc.)

6. Especially suitable for less developed countries or regions.

Potential Advantages of Edible Vaccines

Edible Vaccines For Animals

Edible Vaccines For Human