Edible Vaccines:eating our way to the eradication of

disease

Vaccines

Eradication of small-pox Vaccine preventable diseases

– millions of deaths per year No vaccines

– HIV; ~2 million deaths per year

– malaria; 1.5 - 2.7 million deaths per year

There is a clear need for new vaccines, and vaccination strategies

Why is measles still killing children?

Failure to vaccinate:– fear

• safety and side effects

– misconceptions• prevalence and seriousness

– access/availability

Vaccine failure:– inactivation by heat– interference by maternal antibodies

A subunit based edible vaccine?

economical heat stable oral administration

– no more needles– mucosal immune response

sub-unit vaccine– unable to replicate– overcome maternal antibodies

Developing an edible vaccine for measles

Hemagglutinin (H) protein

• surface exposed protein

• targeted during the immune response

• sufficient to induce protective immunity

H F P

RNA + N L M

select an antigen

Tobacco expressing the MV-H protein

Western blot

50kDa

75kDa

100kDa

PNGase F - + - +

MV-H control

Transgenic tobacco

Feeding tobacco induces MV neutralising antibodies in mice

1

10

100

1000

0 49 78

days after initial feeding

MV

neu

tral

isat

ion

titre

MV-H control

Feeding tobacco may also induce a mucosal immune response

1

10

100

1000

10000

1 2 3 4 5 6 7 8 9

secr

eto

ry I

gA t

itre

MV-H Control Naive

titr

e

Treatment groups

Edible species

lettu

ce

toba

cco

con t

rol

MV-H75kDa

50kDa

From model system to practical vaccine

rice

con t

rol

Edible species – intraperitoneal experiment

From model system to practical vaccine

0

0.5

1

1.5

2

2.5

3

10 100 1,000 10,000

reciprocal serum dilution

abso

rban

ce (

655n

m)

MV-H tobacco

MV-H lettuce

control lettuce

MV-specific serum IgG titers

1

10

100

1000

10000

1 2 3 4 5 6 7

Edible species – intraperitoneal experiment

From model system to practical vaccine

MV-H lettuce control lettuce

MV-neutralisation titers

From model system to practical vaccine

an edible species delivery and dose issues

– quantity and number• higher antigen expression in plants

• targeting the antigen for better uptake

safety issues quality control and licensing GMO issues

Summary: tobacco, lettuce and rice can express the

MV-H protein

plant-derived MV-H protein is able to induce MV neutralising antibodies in mice

edible vaccines have the potential to address the limitations of the current measles vaccine

Acknowledgements

Viral Vaccine Unit,

(Monash University)

Steve Wesselingh

Jenny Martin

Diane Webster

Michelle Cooney

Zhongjun Huang

CSIRO, AdelaideIan Dry

Terri King

Steve Choimes

Melbourne UniversityRichard Strugnell