INTERNATIONAL SOCIETY FOR PLANT MOLECULAR FARMING Issue 11

In this issue

P1 – Medicago announces Phase 3 study

P2 - PlantPraxis announcement

P3 – Polio Vaccine work at the John Innes Centre

P5 – Leaf Expression Systems News

P5/P6 - Conference feedback from bursary awards

P7 - Details of ISPMF’s 2018 conference in Helsinki

P8 – Postdoctoral and PhD opportunities – University of Lleida

Dear ISPMF Members

Welcome to the November issue

of the Newsletter. As you will see,

this issue starts with several

updates regarding the scaling-

up and commercialisation of the

production of plant-made

pharmaceuticals. To me this

represents an encouraging sign

that plants are coming of age as

an expression platform. There

follow two conference reports

that highlight the fact that plant-

based expression is becoming

increasingly “respectable” and

mainstream. The final piece

gives details of the 3rd ISPMF

International Conference that

will take place in Helsinki,

Finland, June 11th – 14th, 2018. I

hope that as many of you as

possible can attend this meeting

as it represents a wonderful

opportunity for both scientific

and social engagement.

Finally, I wish to thank Penny

Hundleby for her excellent work

in producing the newsletter and

to wish you all the best for the

upcoming festive season.

George Lomonossoff

President ISPMF

QUÉBEC CITY (September 26,

2017) – Medicago, a Canadian

biopharmaceutical company

and leader in the development

and production of plant-based

vaccines and therapeutics, is

proud to announce the start of a

Phase 3 efficacy study for its

seasonal quadrivalent influenza

vaccine (QIV) candidate. The

trial is currently taking place with

10,000 subjects in seven

countries (Canada, US, UK,

Germany, Finland, Thailand, and

the Philippines). This efficacy

study is in support of Medicago’s

flu program and expected

launch of the vaccine in time for

the 2020 influenza season in

Canada, USA and Europe.

“Reaching this critical stage with

our QIV flu vaccine is a very

exciting time for us as a

company,” said Bruce D. Clark,

President and CEO of Medicago.

“We are convinced that bringing

this novel vaccine to market will

offer many advantages over

current vaccines and benefits for

those most at risk from the

influenza virus.”

Medicago’s QIV candidate is

produced using a novel virus-like

particle (VLP) technology. VLPs

MEDICAGO ANNOUNCES

PHASE 3 STUDY OF VLP QUADRIVALENT INFLUENZA

VACCINE

ISPMF NEWSLETTER | Issue 11 2

represent a new approach to

vaccine development and

production. VLPs mimic the

native structure of viruses,

allowing them to be easily

recognized by the immune

system. However, they lack the

core genetic material, rendering

them non-infectious and unable

to replicate. In other words, they

are safe and highly effective as

they induce an immune

response similar to a natural

infection.

An alternative to egg-based and

cell-based production systems,

Medicago’s manufacturing

platform brings many

advantages, including much

shorter lead time, reliability and

versatility. It currently takes only

5-6 weeks for the company to

produce a clinical-grade

vaccine, compared to 5-6

months using egg-based

production methods.

With influenza viruses constantly

mutating, Medicago's rapid

technology enables the creation

of a vaccine that precisely

matches the specific strain in

circulation. During a Phase 2

study, the antibody and cell-

mediated immunity (CMI)

responses to Medicago’s VLP

vaccine were higher than the

responses using a comparator

vaccine.

“We are excited to demonstrate

the efficacy of the VLP vaccine

during a large-scale field trial

and prove the benefits of the

unique immune response

induced by this innovative

product,” said Nathalie Landry,

Medicago’s Executive Vice

President of Scientific and

Medical Affairs.

Based in Quebec City,

Medicago announced a major

expansion project in 2015 for a

new headquarters and

commercial production facility

to meet demand and

complement its present

production manufacturing plant

located in North Carolina.

Joint venture to

develop plant-made

pharmaceuticals in

Brazil

Construction is under way on a

state-of-the-art

biopharmaceutical lab and pilot

production facility in Rio de

Janeiro that will support the

development of key biosimilar

and biobetter protein drugs for

the Brazilian market, through a

joint venture between Canadian

biotech company PlantForm

Corporation and Brazil-based Axis

Biotec Brasil.

The new laboratory and

manufacturing facility, supported

by funding from Finep (Brazilian

Funding Agency for Studies and

Projects) is expected to be

completed by the end of 2017. It

marks a major milestone in an

initiative first announced last year,

when Finep provided a US$1-

million grant to Silvestre Labs, part

of the Axis Biotec Brasil group of

companies. The joint venture,

called PlantPraxis, will first develop

a biosimilar version of

adalimumab (Humira®) for

rheumatoid arthritis and other

inflammatory disorders using

PlantForm’s vivoXPRESS®

manufacturing platform for plant-

made pharmaceuticals.

The new facility will be operational

in 2018, with several additional

biological targets in the pipeline.

The long-term goal is to establish a

commercial scale manufacturing

plant in Brazil to serve the South

American market, and a facility in

Canada for the North American

and European markets.

Rio de Janeiro

By Stacey Curry Gunn PlantForm Corporation

ISPMF NEWSLETTER | Issue 11 3

Plant-produced polio

vaccines could help

eradicate age old

disease

Plants have been used to

produce a new vaccine against

poliovirus in what is hoped to be a

major step towards global

eradication of the disease.

A team of scientists, including Dr

Johanna Marsian working in

Professor George Lomonossoff’s

Lab at the John Innes Centre, has

produced the novel vaccine with

a method that uses virus-like

particles (VLPs) - non-pathogenic

mimics of poliovirus which are

grown in plants.

Genes that carry information to

produce VLPs are infiltrated into

the plant tissues. The host plant

then reproduces large quantities

of them using its own protein

expression mechanisms.

Professor Lomonossoff, from the

John Innes Centre said: “This is an

incredible collaboration involving

plant science, animal virology and

structural biology. The question for

us now is how to scale it up - we

don’t want to stop at a lab

technique.”

VLPs look like viruses but are non-

infectious. They have been

biologically engineered so they

do not contain the nucleic acid

that allows viruses to replicate. This

means that they mimic the

behaviour of the virus, stimulating

the immune system to respond

without causing an infection of

poliomyelitis.

Laboratory tests demonstrated

that the poliovirus mimics

provided animals with immunity

from the disease paving the way

for human vaccines to be

produced by plants on a major

scale with the input of

pharmaceutical industry

collaborators.

The breakthrough was made by a

consortium funded by the World

Health Organisation (WHO) which

is seeking to eradicate a disease

that has been known since

antiquity.

The WHO is seeking alternative

vaccines that avoid use of the live

virus as part of an international

drive to completely eradicate the

virus worldwide.

A global scourge up to the middle

of the last century, poliovirus has

been reduced by 99 per cent

since 1988 due to the Global Polio

Eradication Initiative led by the

WHO. Current polio vaccines,

however, require the production

of huge quantities of the virus.

Using the live virus not only

represents a risk of the virus

escaping, the use of the live

attenuated (weakened) virus,

effectively maintains polio in the

global population.

VLPs were expressed at the John

Innes Centre using Hypertrans®

transient plant expression system

which had previously been

developed there. This successful

development not only holds

promise for the production of

vaccines for polio: it could

become a frontline diagnostic

resource in producing vaccines

against other viral outbreaks.

“The beauty of this system of

growing non-pathogenic virus

mimics in plants, is that it boosts

our ability to scale-up the

production of vaccine candidates

to combat emerging threats to

human health,” said Prof

Lomonossoff.

In the past 20 years plants have

become serious competitors to

bacteria, insect cells, yeast or

mammalian cells as production

systems for pharmaceutical

materials. They are cost-effective

requiring simple nutrients, water,

carbon-dioxide and sunlight for

efficient growth and the transient

expression system can be

adjusted rapidly with low costs.

The work at the John Innes Centre

furthered work of scientists at the

University of Leeds, who first

discovered a way of producing

the virus-like particles (VLP) using

the Hypertrans® expression

system.

Despite successes of plant-based

expression to produce VLPs of

papilloma and hepatitis B viruses,

poliovirus VLPs had previously

proved too unstable to make

practical vaccines using this

technique. A problem is that the

genetic material which causes

replication of the virus and which

is therefore absent from the VLPs,

also has a role in holding the

particles together.

However, teams from The National

Institute for Biological Standards

and Control, and the University of

Leeds identified mutations within

protein coats which enabled the

production of VLPs which are

sufficiently stable to act as

vaccines. Experiments at the

University of Oxford showed that

these were identical to native

poliovirus retaining their shape

when warmed, and which are

effective in protecting animals

against poliovirus.

The team used cryo-electron

microscopy at Diamond Light

Source’s Electron Bio-Imaging

ISPMF NEWSLETTER | Issue 11 4

Centre (eBIC) to obtain a clear

look at the structure of the VLPs.

They confirmed the structure and

showed that the external features

of the particles were identical to

those of poliovirus.

Dave Stuart, Director of Life

Sciences at Diamond and

Professor of Structural Biology at

University of Oxford said, “We

were inspired by the successful

synthetic vaccine for foot-and-

mouth disease, also investigated

at Diamond as part of UK research

collaboration. By using Diamond’s

visualisation capabilities and the

expertise of Oxford University in

structural analysis and computer

simulation, we were able to

visualise something a billion times

smaller than a pinhead and

further enhance the design atom

by atom of the empty shells.

Through information gained at

Diamond, we also verified that

these have essentially the same

structure as the native virus to

ensure an appropriate immune

response.”

This collaboration means

manufacturing the particles

stabilised in plants on a large

scale as precursors to vaccines is

now much closer to becoming a

reality. The results are outlined in

the journal Nature

communications: Plant-made

Polio 3 stabilised VLPs - a

candidate synthetic Polio

vaccine.

The collaboration includes the

John Innes Centre, The National

Institute for Biological Standards

and Control, Oxford University,

University of Leeds, Diamond Light

Source, the Henry Wellcome

Building for Genomic Medicine.

a = Virus Like Particles (VLPs) in vitreous ice. b = Reconstruction of poliovirus. c = VLP showing empty internal surface. d and e = Resolutions of poliovirus

This work was published in Nature Communications

ISPMF NEWSLETTER | Issue 11 5

Leaf Expression Systems are soon

to mark their 1st Year Anniversary,

having moved in to their state of

the art facility on the Norwich

Research Park in December 2016.

A regular sight of the facility is the

constant sea of green from the N.

Benthamiana plants growing

under the special conditions within

the CER’s. It would take some

mathematics to work out just how

many seeds, plant pots and trays

along with cubic metres of soil

and water LES has got through

within its first year!

Three grants were successfully

awarded to LES in its first year,

including one in conjunction with

JIC and Prof. George

Lomonossoff’s lab. Other projects

bubble away in the background

with more products developing

behind the scenes. In particular, a

2G12 HIV neutralizing antibody

being developed for the

prevention of AIDS. Read More

here

Our office space is now fully

occupied with a team of 8+

people – two of which are

apprentices who commenced in

August as Laboratory Technicians

and we are still planning to recruit

more! Meet our staff here

Numerous events and

conferences have been attended

such as Plant Based Vaccines and

Antibodies and Biologics (PBVAB),

ECCMID, KTN, CBMNet, with

Innovate 2017 coming up

soon. We’re currently gearing up

for the 14th Annual bioProcessUK

Conference with BIA at the end of

November where we are

exhibiting, so be sure to come and

see us. In addition, our events

calendar for 2018 is currently

being finalised.

Not only did we change our

trading name from Leaf Systems

to Leaf Expression Systems, but

with that have undergone a

complete rebranding with a new

website

www.leafexpressionsystems.co.uk

launched in August and our first

quarterly Newsletter on all our

latest news and products issued in

October. Sign up to our

newsletter here

If you would like to contact us

please do at

info@leafexpressionsystems.com

or get in contact on +44 (0)1603

859379.

The first Asian

conference for Plant

Made Pharmaceuticals

(PMPAsia 2017)

Written by Prof. MoonSik Yang

The first Asian conference for Plant

Made Pharmaceuticals was held

on 22nd-23rd September, 2017 in

Pohang, Republic of Korea. One

hundred seventy nine participants

attended the meeting including

four keynote speakers, Julian Ma,

Yuri Gleba, Qiang Chen and Rejko

Reljic. There were 5 plenary

lectures and 11 oral talks in

addition to 25 posters. Participants

came from Japan, China,

Vietnam, Thailand, Taiwan and

Lebanon in addition to Korea.

There were many graduate

students who were inspired by the

state of the art talks given by the

panel of renowned international

scientists.

In addition to lots of interesting

scientific data, there was active

discussion about governmental

regulation to get product

approval. There was a field trip in

the afternoon of 22nd to the

POSCO steel mill, and a cultural

tour of Kyungju, a fifteen hundred

year old and heritage city on the

morning of 23rd of September.

We are grateful to the ISPMF for

their generous support of the

meeting. The conference was also

supported by three plant

molecular farming companies

which are very active in Korea,

each of whom held a booth to

illustrate their products.

This meeting served as an

important focus for Asian plant

molecular farming scientists for

exchange of scientific data and

initiation of commercialization of

molecular farming products. As

the head of the organizing

committee, I am confident that

we will continue the conference,

indeed a second conference is

now being planned, which will be

held in Japan or China.

Prof. MoonSik Yang is the head of

the organizing committee for

PMPAsia 2017, and received

financial support for the meeting

from ISPMF.

ISPMF NEWSLETTER | Issue 11 6

The 11th Molecular and Cellular

Biology of Helminths congress took

place at the Bratsera Hotel on the

island Hydra, Greece. This

congress, started in 1997, and

since 2014 has become an annual

congress organised on Hydra. The

congress included 12 thematic

sessions and two poster session at

the roof top of a museum with a

nice view over the city of Hydra

and the sunset above the sea. All

participants, limited to 100

people, were strongly

encouraged to give a plenary talk

or present a poster. I believe that

contributing to the congress

ensured that all participants were

involved, which was seen during

the poster session where all

posters were visited. Furthermore,

it was easier to start a

conversation and connect with

other participants. Every session

was opened by a keynote

speaker, who could discuss their

life time research line. Other talks

in the sessions were focused on

early carrier scientist who could

discuss their latest work. In the

session about “genomics, gene

expression and engineering”, the

organisers gave me the

opportunity to present my work

about “the characterisation of

Schistosoma mansoni

fucosyltransferases for glyco-

engineering of native helminth N-

glycan structures in plants”. I

showed that with the

characterisation of

fucosyltransferases we now can

make proteins with LeX, LDN-F, F-

LDN and F-LDN-F glycan motifs in

plants. Furthermore, I discussed

the two recent publications of our

group, in which we show that we

can produce the three major egg

antigens of S. mansoni in plants,

with helminth glycan motifs.

After my talk, the first question was

about the amount of protein we

can produce per plant. For this

community high yields are

important, because for instance

isolation of 1mg ES-62 from the

secretions of a nematode takes 3

months and isolation of omega-1

from the eggs of S. mansoni

doesn’t give enough protein to

perform proper in vivo studies.

Furthermore, to obtain these

proteins from natural source the

entire life cycle of the worm needs

to be maintained in the lab. So

hosts like mice and hamsters, and

intermediate hosts like snails and

ticks need to be infected with

worms and monitored, which is

very time consuming. During the

rest of the congress I talked with

many people interested in

glycoprotein production in plants

and adjustment of glycosylation.

Conference participants

So to summarise, for me this was a

really interesting conference to

attend, the conference offered a

nice atmosphere which stimulated

discussions and meeting other

participants. I learned a lot about

helminths and their molecular and

cellular biology and showed the

community that plants can be

used as an alternative platform to

produce helminth glycoproteins.

Poster session in the sunshine

ISPMF Bursary award By Kim van Noort PhD student, Wageningen University & Research, The Netherlands

ISPMF NEWSLETTER | Issue 11 7

3rd ISPMF

International

Conference

HELSINKI, FINLAND,

June 11th – 14th, 2018

It is our pleasure to announce the

3rd ISPMF conference to be held in

Helsinki, Finland hosted by VTT

Technical Research Centre of

Finland Ltd (www.vtt.fi ). Helsinki is

the precious jewel of Baltic Sea

that can be conveniently

reached with direct flights from

most of the European metropolis.

Helsinki is also called “Daughter of

the Baltic” and it is located on the

tip of the peninsula and on 315

islands. Helsinki is Finland´s major

political, educational, financial,

cultural, and research centre.

The conference program will be

structured to cover both plant-

produced biopharmaceuticals

and other protein groups as well

as latest achievements in

biotechnology of natural

products. We will invite

internationally recognised top

professionals and visionaries as key

note lecturers both from

academia and industry. In

addition, we will select

approximately 25 talks based on

submitted abstracts and have a

separate poster session with 5

minute elevator talks for selected

5 to 8 posters.

The web page for the conference

will be opened in December 2017.

Please follow the updates in the

ISPMF website.

The conference venue will be

located in the Heart of the Helsinki

City Centre at Helsinki Congress

Paasitorni: www.paasitorni.fi

The venue is a culturally and

architecturally interesting granite

Jugend building dating back to

1908.

In connection to the conference

venue there are several suitable

hotels (Scandic Paasi, Cumulus

Hakaniemi, Hilton Helsinki Strand

and Arthur) for accommodation

and we have made a preliminary

booking in them. More information

will be available on the

conference web page when

available.

Important dates:

15th

March,

2018

Submission deadline for

oral presentations

16th April,

2018

Notification of oral

presentation

acceptance

23rd April,

2018

Deadline for applying

ISPMF bursaries

4th May,

2018

Deadline for submission

of poster abstracts only

11th May,

2018

Notification of ISPMF

bursaries

11th May,

2018

Deadline for

registration

25th May,

2018

Notification of poster

acceptance and

selected elevator talks

1st June,

2018

Final program released

11th - 14th

June,

2018

Conference

For more information about

Finland

www.visitfinland.com/about-

finland/

What makes us special:

Aurora Borealis

Midnight Sun

Finnish Sauna

Clean lakes

Wild nature

Finnish design

The one and only real

Santa Claus!

Please mark the dates in your

calendars and start preparing

your fabulous talks. We hope to

see you all in our beautiful capital

at the time of the Midnight Sun.

For details about Sponsorship and advertising opportunities for this meeting please contact the

conference hosts Kirsi-Marja and Anneli

ISPMF NEWSLETTER | Issue 11 8

Postdoctoral and PhD positions – plant

biotechnology – University of Lleida

The Applied Plant Biotechnology Laboratory, University

of Lleida, Lleida, Spain seeks a postdoctoral

scientist with expertise and a documented track

record in corn transformation to join a project

funded by the Bill & Melinda Gates Foundation to

engineer biological nitrogen fixation. Preference

will be given to suitably qualified candidates with

documented experience in plant molecular biology

and the genetic transformation of maize. The post is

offered for an initial period of 2 years with the

possibility of extension contingent on performance.

Only candidates fulfilling the above requirements for

the position will be considered.

We also seek two highly‐motivated students interested

in pursuing a PhD degree in plant molecular

biology at the University of Lleida. The first position

concerns the production of recombinant

proteins in cereals for molecular pharming

applications. The second position focuses the

metabolic

engineering of cereal crops using the latest genome

editing technologies. Candidates should hold a

Bachelor of Science degree with a grade higher than

8.0/10.0 and should also have a Master’s

degree in biological sciences.

Candidates interested in these positions should

forward a detailed curriculum vitae and a

motivation letter, including the names and e‐mail

addresses of three professional referees, to

Paul Christou (christou@pvcf.udl.es) as soon as

possible. The anticipated starting date will be early

to mid‐2018. Salary and benefits will be

commensurate with Spanish Ministry of Economy and

Competitiveness scales.

To

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