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1 Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK Welcome to the Symposium Table of Contents 2 About LibPubMedia 3 General Information 3 Insurance and Liability 3 Disclaimer 4 Copyright Information 4 Map 5 Distinguished Speakers 6 Agenda (Summary) 8 Agenda (With Abstracts) Keynote Speakers Scientific Organisers and Symposium Co-Chairs Dr Nigel Temperton and Dr Simon Scott Viral Pseudotype Unit, Medway School of Pharmacy University of Kent, United Kingdom

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Page 1: Welcome to the Symposiumlpmhealthcare.com/wp-content/uploads/2014/09/RV14-Agenda.pdf · 2014-09-06 · antibodies. By comparison, individuals with serologic evidence of recent exposure

1

Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

Welcome to the Symposium

Table of Contents

2 About LibPubMedia

3 General Information

3 Insurance and Liability

3 Disclaimer

4 Copyright Information

4 Map

5 Distinguished Speakers

6 Agenda (Summary)

8 Agenda (With Abstracts)

Keynote Speakers

Scientific Organisers and Symposium Co-Chairs

Dr Nigel Temperton and Dr Simon Scott

Viral Pseudotype Unit, Medway School of Pharmacy

University of Kent, United Kingdom

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Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

About LibPubMedia

LibPubMedia is an Oxford-based network of scientists providing a portfolio of

services to the biopharmaceutical, biotechnology, academic and government

sectors, including conferences, workshops, symposia, event planning and

management, consultancy and recruitment since 2006.

Web: www.lpmhealthcare.com

Email: [email protected]

Tel: +44 (0)1865 600222

Twitter: @LPMHealthcare

Company Reg No: 07711306

VAT Reg No: 140071464

Registered Address: Rectory Mews, Crown Road, Oxfordshire OX33 1UL, UK

LibPubMedia and LPMHealthcare are trading names of LibPubMedia Ltd.

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Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

General Information

WiFi Code and instructions for internet access via your laptop/mobile device will be available from

the registration desk.

Event Dates: 08 September 2014

Event Website: http://lpmhealthcare.com/respiratory-viruses-2014/

Venue: Lady Brodie Room, The Hall Building, St Hilda's College Oxford, Cowley

Place, Oxford, OX4 1DY, England, UK

Tel: +44 (0) 1865 276884, Website: http://www.st-hildas.ox.ac.uk

Registration Desk: Located outside Lady Brodie Room

Accommodation: If you are staying at St Hilda’s College, please ask the receptionist for

directions upon arrival. For resident delegates, self-service breakfast will

be available in the College Dining Hall between 7.30am-8.00am. Please

vacate your rooms by 10.00am on the day of your departure to avoid

additional charges by the college and leave your keys at the Porter’s

Lodge.

Name Badges: The College requests all delegates to wear name badges while on the

premises to avoid any confusion.

Mobile Phones: Please switch off your mobile phone during oral presentations.

Health and Safety: Please familiarise yourself with the emergency exits. If you are staying in

the College, please read any Health and Safety notices displayed in your

room.

Smoking: In addition to any local venue regulations, UK no-smoking regulations

apply on the College premises.

Insurance and Liability: Participants are responsible for taking appropriate insurance cover (including

health insurance) in connection with their attendance of this event. The event organisers and hosts, or St

Hilda’s College shall not be liable for any kind of loss or damage to the personal property of the

participants. Event participants shall be responsible for compensating any loss, should they cause any

damage to the host’s property or the venue.

Disclaimer: The information specified in oral and poster presentations, written abstracts, biographies and

exhibitions come from diverse sources and it is not in the capacity of event organisers to validate it, and is

provided on an ‘as-is’ basis. Therefore, the event organisers accept no responsibility for literary or scientific

correctness of this information, and shall have no liability of any kind, should any of the information be

incorrect. The event organisers and hosts make no representation or warranty of gain of business or profits

as a result of use of services or information provided in connection with the even and shall not be liable for

any direct or indirect damages, loss of business, employment, profits or anticipated savings resulting from

the use of the services or information provided in connection with the event, in any country or court of law.

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Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

Furthermore, the materials contained in the event handbook are provided on the understanding that

speakers or presenters have the right to their presentation in this manner. Therefore, event organisers and

hosts shall not be liable, in any country or court of law, for infringement of third party rights by an event

presenter, participant, sponsor, supporter or exhibitor.

© 2014 Copyright Information: Contents of this document are copyright of the presenters, sponsors,

instructors and/or LibPubMedia Ltd, unless explicitly stated otherwise. No part of this document may be

reproduced in any form or by any means, electronically, mechanically, by photocopying, recording or

otherwise, modified, adapted, resold, shared, performed or displayed in public, transmitted or displayed by

audio or video, for commercial or non-commercial purposes, without the prior written permission of the

copyright owners.

Map

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Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

Distinguished Speakers

Session 1: Chair Dr Nigel Temperton

10.00: Professor Sarah Gilbert (Keynote Speaker), University of Oxford, UK

10.40: Dr Karen Laurie, WHO Collaborating Centre for Influenza, Australia

11.00: Dr Qibo Zhang, University of Liverpool, UK

11.20: Dr Adrian Shepherd, Birkbeck College (University of London), UK

11.50: Dr Francesca Ferrara, University of Kent, UK

12.10: Dr I-Na Lu, National Health Laboratory, Luxembourg

12.30: Professor Xiao-Ning Xu (Keynote Speaker), Imperial College London, UK

Session 2: Chair Dr Simon Scott

14.00: Dr Geraldine Taylor, The Pirbright Institute, UK

14.30: Miss Rebecca Kinsley, University of Kent, UK

14.40: Dr David Griffiths, Moredun Research Institute, Scotland, UK

15.00: Professor Maria Zambon, Public Health England, UK

16.10: Dr Kerstin Beer, MRC National Institute for Medical Research, UK

16.30: Dr Lynda Coughlan, University of Oxford, UK

16.50: Dr Richard Pebody, Public Health England, London, UK

17.20: Close

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Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

Agenda (Summary)

08 September 2014, Lady Brodie Room, The Hall Building

09.15 – 09.45: Registration, welcome coffee and networking

09.45: Welcome and housekeeping

09.50: Opening by symposium co-chairs

Session 1: Chair Dr Nigel Temperton

10.00: Professor Sarah Gilbert (Keynote Speaker)

University of Oxford, UK

Measurement of immune responses in the development of improved influenza vaccines

10.40: Dr Karen Laurie

WHO Collaborating Centre for Influenza, Peter Doherty Institute for Infection and

Immunity, Melbourne, Australia

Improving standardisation and timeliness of Seroepidemiological studies through the Global

Partnership CONSISE (the Consortium for the Standardization of Influenza Seroepidemiology)

11.00: Dr Qibo Zhang

University of Liverpool, UK

Cross-reactive immunity against influenza viruses in children and adults following 2009 pandemic

H1N1 infection

11.20: Dr Adrian Shepherd

Birkbeck College (University of London), UK

Immunoinformatics and computational virology: making a contribution to surveillance and vaccine

design

11.50: Miss Francesca Ferrara

University of Kent, UK

Pseudotypes as tools to study heterosubtypic immunity

12.10: Dr I-Na Lu

National Health Laboratory, Luxembourg

Generation of hemagglutinin stalk specific CD4+ T cell immune responses during sublethal dose

influenza A virus infection

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Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

12.30: Professor Xiao-Ning Xu (Keynote Speaker)

Chair in Human Immunology, Department of Medicine, Imperial College London, UK

T-cell responses in the human flu challenge model

13.10: Lunch

Session 2: Chair Dr Simon Scott

14.00: Dr Geraldine Taylor

Vaccinology group, The Pirbright Institute, UK

Replication-Defective Chimpanzee Adenovirus and MVA Vectors Expressing Human (H)RSV

Antigens Protect Calves Against (B)RSV Infection

14.30: Miss Rebecca Kinsley

University of Kent, UK

The contribution of specific haemagglutinin mutations to equine influenza vaccine breakdown

14.40: Dr David Griffiths

Moredun Research Institute, Scotland, UK

Retrovirus-induced lung cancer in sheep

15.00: Professor Maria Zambon

Director, Reference Microbiology Laboratory, Public Health England, UK

Middle East respiratory syndrome coronavirus

15.40: Coffee, networking

16.10: Dr Kerstin Beer

MRC National Institute for Medical Research, UK

Generation and characterisation of monoclonal antibodies recognising neutralising epitopes of

currently circulating Influenza A (H3N2) viruses

16.30: Dr Lynda Coughlan

University of Oxford, UK

An update from clinical trials using viral vectored vaccines for influenza

16.50: Dr Richard Pebody

Public Health England, London, UK

The seroepidemiology of acute respiratory viruses: what is the public health rationale?

17.20: Closing remarks

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Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

Agenda (With Abstracts)

08 September 2014, Lady Brodie Room, The Hall Building

09.45: Welcome and housekeeping

09.50: Opening by symposium co-chairs

Session 1: Chair Dr Nigel Temperton

10.00: Professor Sarah Gilbert (Keynote Speaker)

University of Oxford, UK

Measurement of immune responses in the development of improved influenza vaccines

Abstract: The methods for determining immune response to licensed influenza vaccines have

changed very little over past decades. However with the development of novel vaccines designed

to induce broader immunity, whether within clade or cross clade immunity, new assays are also

being developed and implemented. The methods now in use for testing new influenza vaccines in

humans, pigs and poultry will be discussed.

10.40: Dr Karen Laurie

WHO Collaborating Centre for Influenza, Peter Doherty Institute for Infection and

Immunity, Melbourne, Australia

Improving standardisation and timeliness of Seroepidemiological studies through the Global

Partnership CONSISE (the Consortium for the Standardization of Influenza Seroepidemiology

Abstract: CONSISE, the Consortium for the Standardization of Influenza Seroepidemiology, is a

global partnership to develop investigation protocols and standardise seroepidemiology to inform

health policy for influenza and other respiratory diseases. CONSISE is comprised of an

epidemiology and laboratory working group. The laboratory working group is focused on

serological assay standardisation and has developed consensus assay protocols and performed

international laboratory comparisons of serological assays to detect antibodies to influenza

viruses. Epidemiological and serological protocols developed by CONSISE members have recently

been used ‘in the field’ to study MERS-CoV and A(H7N9) outbreaks. CONSISE’s materials are open

access and we encourage membership from all interested parties. This applied research may be of

interest to others at the Respiratory Viruses 2014 meeting performing such collaborative studies

to improve seroepidemiology.

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Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

11.00: Dr Qibo Zhang

University of Liverpool, UK

Cross-reactive immunity against influenza viruses in children and adults following 2009 pandemic

H1N1 infection

Muhammad S Ahmed1, Laura C Jacques

1, Waleed Mahallawi

1, Francesca Ferrara

2, Nigel

Temperton2,

Nav Upile3, Casey Vaughan

3, Ravi Sharma

3, Helen Beer

4, Katja Hoschler

5, Paul S

McNamara6, Qibo Zhang

1

Institute of Infection and Global Health, University of Liverpool1, University of Kent

2, ENT

Department, Alder Hey Children’s Hospital3; ENT Department, Royal Liverpool University Hospital

4,

Public Health England, London5, Department of Women’s and Children’s Health, University of

Liverpool6

Abstract: 2009 H1N1 pandemic influenza (A(H1N1)pdm09) resulted in considerable morbidity and

mortality in humans. Recent studies suggest infection with A(H1N1)pdm09 virus elicited cross-

reactive anti-hemagglutinin (HA) memory B cell response to conserved regions of HA. However,

the breadth and magnitude of cross-reactive immunity in children and adults following

A(H1N1)pdm09 infection are unknown. Methods: We investigated serum anti-HA immunity to a

number of group-1 and -2 viruses in children and adults following 2009 pandemics using

hemagglutination inhibition (HAI), enzyme-linked immunosorbent assay and virus neutralization

assay. Results: Applying hemagglutination inhibition (HAI) titres≥40 against A(H1N1)pdm09 as

threshold of sero-positivity, we observed significantly higher levels of anti-HA antibodies to a

number of virus subtypes, including those neutralizing H5N1, in subjects with evidence of

exposure to pandemic H1N1 than those without. Adults demonstrated broader and stronger

cross-reactive anti-HA antibodies than children, including cross-reactive anti-HA1 and -HA2

antibodies. By comparison, individuals with serologic evidence of recent exposure to seasonal

H1N1 or H3N2 did not show such broad cross-reactive immunity. Conclusion: Our results suggest

individuals exposed to A(H1N1)pdm09 virus developed a broad and age-associated cross-reactive

anti-HA immunity which may have important implications for future vaccination strategies to

enable protection against a broader range of influenza viruses.

11.20: Dr Adrian Shepherd

Birkbeck College (University of London), UK

Immunoinformatics and computational virology: making a contribution to surveillance and vaccine

design

Abstract: We analyze large sets of sequences, often mapped to structural data, to gain insights

into the antigenic escape of viral populations driven by herd immune responses. For example,

using our "epitope clustering" method, we aim to predict escape from prevalent antibodies that

target influenza A, and have challenged assumptions about "conserved" vaccine targets on the

stalk of haemagglutinin and the shielding role of N-glycans. We also analyse antibody repertoires

from Next Generation Sequencing data, focusing on two rapidly mutating viruses, influenza A and

HIV. The ultimate aim is to support the design of immunogens capable of guiding the host immune

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Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

response down a particular maturation pathway that culminates in the induction of broadly

neutralising antibodies.

11.50: Miss Francesca Ferrara

University of Kent, UK

Pseudotypes as tools to study heterosubtypic immunity

Francesca Ferrara1, Eleonora Molesti

1, Eva Böttcher-Friebertshäuser

2, Davide Corti

3, Teresa

Lambe4, Sarah C Gilbert

4, Emanuele Montomoli

5 and Nigel Temperton

1

1Viral Pseudotype Unit, School of Pharmacy, University of Kent, Central Avenue, Chatham

Maritime, ME4 4TB, United Kingdom; 2Institute of Virology, Philipps University Marburg, Hans-

Meerwein-Str. 2, 35043 Marburg, Germany; 3Institute for Research in Biomedicine, Via Vela 6,

6500 Bellinzona, Switzerland; 4The Jenner Institute, Old Road Campus Research Building,

Roosevelt Drive, University of Oxford, Oxford, United Kingdom; 5Department of Molecular and

Developmental Medicine, University of Siena, Via Aldo Moro 3, 53100 Siena, Italy

The evidence that by using different approaches it is possible to isolate monoclonal antibodies

binding conserved HA regions and exhibiting heterosubtypic neutralization activity has highlighed

the role of these antibodies in protection against influenza virus infections in the human

population. However classical serological assays, such as haemagglutination inhibition and

microneutralization have demonstrated low sensitivity for the detection of these cross-neutralizing

antibodies directed against epitopes in the haemagglutinin (HA) stalk region. This limits the

opportunity for studing heterosubtypic immunity using seroepidemiological approaches and

furthermore it presents an obstacle to the evaluation of vaccines that elicit these heterosubtypic

antibodies to confer broad protection. Influenza pseudotypes represent safe tools to study the

neutralizing antibody response since they are replication-defective viruses and they harbour on

their envelope only the HA that is the major target of this response. We will show that human and

avian influenza A and B pseudotypes employed as surrogate antigens in neutralization assays are

powerful tools to study the presence and magnitude of heterosubtypic neutralizing antibody

responses in human sera. Additionally we will show how the use of chimeric (head-stalk) HA

pseudotype as antigen in the neutralization assay permits the detection of HA stalk-directed

heterosubtypic antibody responses.

12.10: Dr I-Na Lu

National Health Laboratory, Luxembourg

Generation of hemagglutinin stalk specific CD4+ T cell immune responses during sublethal dose

influenza A virus infection

I-Na Lu, Sophie Farinelle, Claude P Muller

Laboratory of Immunology, Centre de Recherche Public de la Santé (CRP-Santé), Luxembourg

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Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

Abstract: The stalk region of the influenza virus hemagglutinin (HA) is relatively well conserved

when comparing to the globular head domain of HA, and antisera elicited against the HA stalk

region are shown to be cross-protective between strains, which makes it a potential target for the

universal vaccine against influenza. However, despite these encouraging results, studies have not

yet determined the role of CD4+ T cells, which might serve as a vital player in mediating HA stalk-

specific humoral and cellular immune responses. To better understand the CD4+ T cell

immunogenicity of the HA stalk, which might be important for protection from influenza virus

infection, we sought to determine the profile of HA stalk-specific CD4+ T cell responses generated

during sublethal infection of influenza. Using a model of murine influenza virus infection,

significantly increased activation and differentiation of T follicular helper (Tfh) cells were observed

together with the expansion of germinal center (GC) B cells in the lung draining lymph nodes

(dLNs). However, the splenocytes from only half of the infected mice produced IL-2 and IFN-γ after

HA stalk-specific CD4+ T cell stimulation measured by the enzyme-linked immunospot (ELISpot)

assay. The induction of polyfunctional CD4+ T cell subsets was significantly lower in magnitude by

using the HA stalk peptide pool when compared to using the HA recombinant protein. Overall, our

data showed that HA stalk induced low magnitude of CD4+ T cell responses following sublethal

infection of influenza. In order to improve cross-strain protection against influenza virus

infections, the generation of broad and highly polyfunctional CD4+ T cell responses might be

important for the future vaccine design.

12.30: Professor Xiao-Ning Xu (Keynote Speaker)

Chair in Human Immunology, Department of Medicine, Imperial College London, UK

T-cell responses in the human flu challenge model

Abstract: While neutralizing antibodies offer major protective immunity against influenza

infection, the precise role of T cells remains unclear in humans. To address this issue, we

conducted influenza human challenge studies and studied the role of pre-existing and developing

T cell immunity in limiting illness severity. We infected healthy volunteers with no detectable

antibodies to the challenge viruses (live seasonal H3N2 or H1N1 viruses). Our studies identify a

subset of CD4+ T cells that is an important correlate of both homotypic and heterotypic protection

and also provides potentially valuable information for the design of future vaccines against

emerging strains.

13.10: Lunch

Session 2: Chair Dr Simon Scott

14.00: Dr Geraldine Taylor

Vaccinology group, The Pirbright Institute, UK

Replication-Defective Chimpanzee Adenovirus and MVA Vectors Expressing Human (H)RSV

Antigens Protect Calves Against (B)RSV Infection

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Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

Geraldine Taylor1, Michelle Thom

1, Becky Herbert

1, Efrain Guzman

1, Angiolo Pierantoni

2, Stefania

Capone2, Stefano Colloca

2, Riccardo Cortese

3, Alfredo Nicosia

2,4,5 and Alessandra Vitelli

2

1The Pirbright Institute, Ash Road, Pirbright, Surrey, GU24 0NF, UK;

2Okairòs, Naples, Italy;

3Keires

AG, Basel, Switzerland; 4University of Naples Federico II, Italy;

5Ceinge - Biotecnologie Avanzate

s.c.a r.l., Naples, Italy

Abstract: We have evaluated the safety, immunogenicity and efficacy of a novel vectored HRSV

vaccine in calves, a model of natural RSV infection. Bovine (B)RSV is a major cause of respiratory

disease in young calves and is genetically and antigenically closely related to HRSV. We have

generated a novel genetic vaccine consisting of an artificial, consensus-based, HRSV antigen which

includes a soluble F protein for the induction of neutralizing antibodies and the conserved N and

M2-1 internal proteins, which are known to elicit T cell immunity in humans. This complex antigen

is encoded by a replication incompetent chimpanzee Adenovirus (Ad), to which there is limited

pre-existing immunity in man, and by Modified Vaccinia Ankara (MVA) vectors. The vaccine

candidates, which induce protective immunity in mice and cotton rats, were administered to

young, BRSV sero-negative calves in different combinations of homologous or heterologous

prime/boost regimens, with the priming and boosting vector being administered either

intramuscularly (IM) or intranasally (IN). Calves were challenged IN and intratracheally with BRSV,

4 weeks after vaccination. Following challenge, nasopharyngeal excretion of BRSV was monitored

daily and at study end, 6 days after BRSV challenge, BRSV titres in the lung and the extent of

pulmonary pathology were evaluated. The vaccines were immunogenic and induced complete

protection against nasal BRSV replication in calves when administered by Ad-RSV IN prime/MVA-

RSV IM boost regimen. Complete protection against replication of BRSV in the lungs was also

induced by Ad IN/Ad IM, Ad IM/Ad IM and Ad IM/MVA IM regimens. Complete protection against

pulmonary pathology was induced by Ad IN/MVA IM, and the extent of pulmonary pathology was

significantly reduced in calves vaccinated with all regimens. These studies demonstrate that

complete, cross-protective efficacy was induced in calves by a novel virus-vectored HRSV vaccine

and there was no evidence of vaccine-enhanced disease.

14.30: Miss Rebecca Kinsley

University of Kent, UK

The contribution of specific haemagglutinin mutations to equine influenza vaccine breakdown

Rebecca Kinsley1, Stuart Mather

1, Debra Elton

2, Alana Kilby

2, Janet Daly

3, Nigel Temperton

1 &

Simon Scott1

1Viral Pseudotype Unit, School of Pharmacy, University of Kent, Central Avenue, Chatham

Maritime, ME4 4TB; 2Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8

7UU; 3School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington,

LE12 5RD

Abstract: In 1979, influenza caused a major epidemic amongst horses across Europe including

Newmarket, UK. Subsequently, vaccines were produced using multiple outbreak strains including

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Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

A/equine/Newmarket/79 and A/equine/Fontainebleau/1/79 (both subtype H3N8) which

prevented further outbreaks until 1989 when a new antigenic drift variant emerged. The

A/equine/Sussex/89 (H3N8) strain came from one of the affected regions in the UK where both

unvaccinated and, notably, vaccinated horses were affected. The accumulation of mutations

within important antigenic epitopes of the virus surface glycoprotein haemagglutinin (HA) can lead

to a decrease in the efficiency of antibody recognition. Three mutations, previously identified

within five major epitopes of human influenza HA, have been incorporated into equine influenza

pseudotyped lentiviruses (PVs). The PVs were generated via co-transfection of HEK293T cells with

four plasmids expressing the equine influenza HA surface glycoproteins, HIV gag-pol, firefly

luciferase reporter gene and TMPRSS2 endoprotease (to cleave the HA). The resulting viruses

were harvested and pseudotype virus antibody neutralisation assays (PVNAs) against

Newmarket/79 specific sera were performed. Results showed that specific single amino acid

mutations in the putative major epitope sites altered the ability of the sera to neutralise the PVs,

indicating their importance in vaccine protection.

14.40: Dr David Griffiths

Moredun Research Institute, Scotland, UK

Retrovirus-induced lung cancer in sheep

David J Griffiths, Charline Alleaume, Esther Bijsmans, Henny M Martineau, Patricia Dewar, Jeanie

Finlayson, Mark P Dagleish, Chris Cousens

Moredun Research Institute, Pentlands Science Park, Edinburgh, EH26 0PZ, UK

Abstract: Ovine pulmonary adenocarcinoma (OPA) is a common infectious respiratory disease of

sheep caused by jaagsiekte sheep retrovirus (JSRV) and is an important economic and animal

welfare problem for sheep farmers. In addition, OPA is regarded as a valuable natural animal

model for human lung adenocarcinoma. Research in our laboratory is focused on improving

understanding of the pathogenesis of OPA in order to inform the development of diagnostic tests

that can be used to control the disease and reduce its impact on sheep farming. Recent studies

have identified the presence of neutralizing antibodies to JSRV in naturally affected sheep and

identified candidate tumour antigens that have potential application as diagnostic markers. We

have also developed a novel in vitro lung tumour model that reproduces many of the features of

JSRV infection of lung tissue observed in vivo. This model provides a platform for future studies of

early events in OPA oncogenesis and enhances the utility of OPA as a model for human lung

adenocarcinoma.

15.00: Professor Maria Zambon

Director, Reference Microbiology Laboratory, Public Health England, UK

Emerging Virus Infections

Abstract: The International Health Regulations (IHR) were introduced in 2005 in response to the

global epidemic of infection caused by SARS in 2003. The IHR framework was intended to assist

global disease control for newly emerging infections such as Pandemic Influenza and MERS CoV.

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Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

Although IHR have strengthened the surveillance and reporting framework for the detection of

novel infections, there are many challenges that countries face in responding to emerging

infections. This includes risk assessment, risk management and basic health system capacity and

capability. Fragile health systems buckle under unexpected challenges and are most vulnerable to

lack of adequate infection control in the face of unexpected and severe infections. Mobilising the

global clinical and research community will be necessary to to harness recent technical advances

in immunotherapy and develop and deliver interventions for new and emerging infections. Some

of these challenges will be discussed with reference to Mers CoV, Pandemic Influenza and recent

Ebola outbreaks.

15.40: Coffee, networking

16.10: Dr Kerstin Beer

MRC National Institute for Medical Research, UK

Generation and characterisation of monoclonal antibodies recognising neutralising epitopes of

currently circulating Influenza A (H3N2) viruses

Kerstin Beer, Rodney S Daniels, John W McCauley

MRC National Institute for Medical Research, Division of Virology, London NW7 1AA, UK

Abstract: Influenza is an infectious disease of the respiratory tract which is preventable by

vaccination. The main target of vaccine-induced neutralising antibodies (Abs) is the surface protein

haemagglutinin (HA). Sequence comparisons show a number amino acid changes in the HA protein

during the evolution of human influenza A (H3N2) viruses which prevents them from being

recognized by neutralising Abs. A monoclonal Ab (mAb) recognising a neutralising epitope, which

is conserved in a broad spectrum of influenza viruses, would have the potential to prevent and

treat influenza, regardless of the causal strain. In this work a panel of 12 mouse mAbs recognising

neutralising epitopes of current circulating H3N2 viruses was generated by using the hybridoma

technology. A virus neutralising assay and a heamagglutination inhibition assay showed that

almost all of the neutralising mAbs inhibit the receptor binding of recent H3N2 influenza viruses.

Viruses isolated prior to 2006, a time after which a decrease in receptor avidity was seen, were

not recognised. The neutralising epitopes have been identified by generating mAb escape viruses.

Sequence analyses of HA of the escape viruses have determined the haemagglutinin head domain

as the main target of the neutralising mAbs. Further structural analyses of the neutralising

epitopes are planned. The generation and characterisation of mAbs neutralising a broad spectrum

of current circulating H3N2 influenza virus isolates provides important information for the

development of immunotherapy of influenza infections. Information about identified neutralising

epitopes which are conserved in a broad spectrum of currently circulating H3N2 viruses can be

used to design vaccines which induce the production of broadly neutralising antibodies against

influenza viruses.

Page 15: Welcome to the Symposiumlpmhealthcare.com/wp-content/uploads/2014/09/RV14-Agenda.pdf · 2014-09-06 · antibodies. By comparison, individuals with serologic evidence of recent exposure

15

Respiratory Viruses 2014, 08 September 2014, St Hilda’s College, Oxford, UK

16.30: Dr Lynda Coughlan

Postdoctoral Researcher, Jenner Institute, University of Oxford, UK

An update from clinical trials using viral vectored vaccines for influenza

Coughlan L, Payne R, Milicic A, Venkatraman N, Antrobus R, Lugonja B, Hill AV, Lambe T, Gilbert SC

Abstract: Human Adenovirus Type-5 (Ad5) vectors are used most commonly in clinical trials.

Adenoviruses (Ads) are promising vaccine vectors for infectious diseases due to their ability to

induce and boost cellular immunity to transgene antigens. However, high level pre-existing

immunity in humans has the potential to limit the efficacy of Ad5-based vaccines. In recent years

this issue has prompted the investigation of rare species or non-human Ad vectors. We report the

first dose-escalation Phase I clinical trial to determine safety and immunogenicity of replication-

defective chimpanzee Ad, ChAdOx1, expressing conserved antigens from Influenza A,

nucleoprotein (NP) and matrix protein-1 (M1). There were no serious adverse events at any dose

and the vaccine was well tolerated up to 2.5x1010

vp. At the highest dose (5x1010

vp), 3/6

volunteers experienced adverse reactions including fever, fatigue, malaise and headache. Peak T-

cell responses (ELISpot) to NP+M1 peptide pools were observed D14 post-vaccination and were

increased ~3-fold (5x108vp), 6-fold (5x10

9vp), 7-fold (2.5x10

10vp) and 4-fold (5x10

10vp) over

baseline (D0). A small number of volunteers received a boost vaccination with poxviral vector

MVA-NP+M1 ~8 weeks post-prime with ChAdOx1-NP+M1. MVA-NP+M1 boosted T-cell responses

to levels comparable to the initial ChAdOx1-NP+M1 prime vaccination. In a separate clinical trial

we are currently assessing the comparative immunogenicity of ChAdOx1-NP+M1 and MVA-NP+M1

in a prime-boost regimen, which includes four groups receiving boost vaccinations at an interval of

8 or 52 weeks post initial vaccination. Ongoing data from this trial will be presented.

Keywords: adenovirus, vaccine, influenza, clinical

16.50: Dr Richard Pebody

Public Health England, London, UK

The seroepidemiology of acute respiratory viruses: what is the public health rationale?

Abstract: Using examples from established infections such as seasonal influenza plus new and

emerging pathogens such as pandemic influenza and mers -cov, this presentation will outline how

seroepidemiology can be used to address important public health questions.

17.20: Close of symposium