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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
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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
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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
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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
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hosts shall not be liable, in any country or court of law, for infringement of third party rights by an event
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© 2014 Copyright Information: Contents of this document are copyright of the presenters, sponsors,
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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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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.
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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