Impfung: Ergebnisse Optionen Entwicklungen

Vaccination against highly pathogenic avian influenza H5N1 virus
in zoos using an adjuvanted inactivated H5N2 vaccine

Joost Philippa a,b,∗, Chantal Baas a, Walter Beyer a, Theo Bestebroer a, Ron Fouchier a,
Derek Smith a,c, Willem Schaftenaar b, Ab Osterhaus a


a Institute of Virology, Erasmus MC, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands
b Rotterdam Zoo, P.O. Box 532, 3000 AM, Rotterdam, The Netherlands
c Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK
Received 28 November 2006; received in revised form 23 January 2007; accepted 30 January 2007

Abstract
Highly pathogenic avian influenza (HPAI) H5N1 virus infections have recently caused unprecedented morbidity and mortality in a wide range of avian species. European Commission directive 2005/744/EC allowed vaccination in zoos under strict conditions, while reducing confinement measures. Vaccination with a commercial H5N2 vaccine with vaccine doses adapted to mean body weight per species was safe, and proved immunogenic throughout the range of species tested, with some variations between and within taxonomic orders. After booster vaccination the overall homologous geometric mean titre (GMT) to the vaccine strain, measured in 334 birds, was 190 (95% CI: 152–236), and 80.5% of vaccinated birds developed a titre of ≥40. Titres to the HPAI H5N1 virus followed a similar trend, but were lower (GMT: 61 (95% CI: 49–76); 61%≥40). The breadth of the immune response was further demonstrated by measuring antibody titres against prototype strains of four antigenic clades of currently circulating H5N1 viruses. These data indicate that vaccination should be regarded as a beneficial component of the preventive measures (including increased bio-security and monitoring) that can be undertaken in zoos to prevent an outbreak of and decrease environmental contamination by HPAI H5N1 virus, while alleviating confinement measures.


© 2007 Elsevier Ltd. All rights reserved.
Keywords: Avian influenza; H5N1; Vaccination; Zoo; Clade

1 1. Introduction
Avian influenza virus (AIV) is an Orthomyxovirus, which can be classified according to its pathogenicity and the antigenicity of its surface ...

Corresponding author at: Institute of Virology, Erasmus MC, P.O. Box
2040, 3000 CA, Rotterdam, The Netherlands. Tel.: +31 104088069.
E-mail

hmm, 60% fuer Voegel-Impfstoff.
Fuer Menschen haben wir ca 80% (Glaxo,Novartis,Baxter) oder 45%(Sanofi)

inwieweit sind vogel - und Menschen- Impfstoffe gggfs. austauschbar ?

A conventional, inactivated oil emulsion vaccine suppresses
shedding and prevents viral meat colonisation in commercial
(Pekin) ducks challenged with HPAI H5N1

Maria Serena Beato, Anna Toffan, Roberta De Nardi, Alessandro Cristalli,
Calogero Terregino, Giovanni Cattoli, Ilaria Capua∗

Istituto Zooprofilattico Sperimentale delle Venezie, Via dell’Universita` 10, 35020 Legnaro, Padua, Italy
Received 15 September 2006; received in revised form 5 February 2007; accepted 8 February 2007

Abstract
The ongoing H5N1 Asian epidemic is currently affecting a number of avian species, including waterfowl. These birds appear to have an important role as reservoirs of infection and comprehensive data on the efficacy of vaccination is currently lacking. The present paper reports the effect of a two doses vaccination programme with a conventiona inactivated product on infection, lateral spread, shedding and presence of virus in commodities such as meat and viscera of Pekin ducks. Vaccination of this species appears to be efficacious in suppressing viral
shedding, and preventing viraemia and lateral spread of infection to unvaccinated and vaccinated Pekin ducks.


© 2007 Elsevier Ltd. All rights reserved.
Keywords: Avian influenza; Vaccination; Pekin ducks; Food safety

1. Introduction
Avian influenza (AI) infections of domesticated birds caused by highly pathogenic viruses of the H5N1 subtype are now present in number of countries in Asia, Europe, Middle East and Africa. The viruses that are cur6rently circulating, have originated from a common progenitor
A/goose/Guangdong/1/96 (H5N1), which through genetic...

The use of vaccination to combat multiple introductions of Notifiable
Avian Influenza viruses of the H5 and H7 subtypes
between 2000 and 2006 in Italy3

Ilaria Capua ∗, Stefano Marangon
OIE/FAO Reference Laboratory for Newcastle Disease and Avian Influenza, Istituto Zooprofilattico Sperimentale delle Venezie,
Viale dell’Universit`a 10, 35020 Legnaro, Padova, Italy

Received 18 July 2006; received in revised form 20 November 2006; accepted 29 January 2007

Abstract
Since 1999, Italy has been challenged by several epidemics of Notifiable Avian Influenza (NAI) of the H5 and H7 subtypes, occurring in the densely populated poultry areas of northern part of the country. Vaccination with a conventional vaccine containing a seed strain with a different neuraminidase subtype to the field virus was used to complement biosecurity and restriction measures as part of an overall eradication strategy. This vaccination technique, known as the “DIVA—Differentiating Infected from Vaccinated Animals” system, enabled, the identification of field exposed flocks and ultimately the eradication of H7N1, H7N3 and H5N2 infections. A bivalent H5/H7 prophylactic vaccination programme of defined poultry populationswas introduced subsequently to increase their resistance to field infection. Retrospective
analysis of the outbreaks identified important reservoir species such as quail, and demonstrated clearly the higher susceptibility of turkeys to infection.

Data generated during 6 years of experience with vaccination against Avian Influenza (AI) indicate that it is a useful tool to limit secondary
spread and possibly prevent the introduction of AI viruses in a susceptible population. The Italian AI control programme including vaccination was managed in a flexible manner and enabled the continuation of international trade. It is imperative that if vaccination is to be used to combat the current H5N1 epidemic it is used in conjunction with other measures and under official supervision. An extraordinary effort is required from international organisations to accredit control strategies so that harmonised and validated programs can be implemented. Transparency and sharing of field results from countries that are practising such programmes is crucial to the progressive control and ultimately the eradication of NAI infections in the animal reservoir.


© 2007 Published by Elsevier Ltd.
Keywords: Avian influenza; Vaccination; Control; Epidemiology

Contents
1. Introduction
2. Emergency vaccination programmes
3. 2002–2003 H7N3 LPAI epidemic
4. From emergency to prophylactic vaccination
5. Re-occurrence of the H7N3 LPAI virus and introduction of LPAI H5N2
6. Discussion
References

A Diagnostic Aid for Differentiating Infected from Vaccinated Poultry Based on Antibodies to the Nonstructural (Ns1) Protein of Influenza a Virus
TUMPEY, TERRENCE - CDC - ATLANTA, GA
ALVAREZ, RENE - CDC - ATLANTA, GA
Swayne, David
Suarez, David


http://www.ars.usda.gov/research/pub..._NO_115=167705
Journal of Clinical Microbiology February 10, 2005 Citation: Tumpey, T., Alvarez, R., Swayne, D.E., Suarez, D.L. 2005. A diagnostic aid for differentiating infected from vaccinated poultry based on antibodies to the nonstructural (ns1) protein of influenza a virus. Journal of Clinical Microbiology. 43:676-683. Interpretive Summary: Killed avian influenza virus vaccines are used in some parts of the world to protect birds from avian influenza. Serological tests to monitor success of vaccination cannot distinguish between vaccinated birds and birds infected with the live virus. A new ELISA test was developed that detected antibodies against NS1 protein of avian influenza. Vaccinated birds were negative for NS1 antibodies but virus-infected birds had antibodies to the NS1 protein. This new test can be used to differentiated infected from vaccinated animals (DIVA). Technical Abstract: Not required.

Overview of avian influenza DIVA test strategies
David L. Suarez*
USDA/ARS, Southeast Poultry Research Laboratory, 934 College Station Road, Athens, GA 30605, USA
Accepted 18 August 2005

Abstract
The use of vaccination in poultry to control avian influenza has been increasing in recent years. Vaccination has been primarily with killed
whole virus-adjuvanted vaccines. Proper vaccination can reduce or prevent clinical signs, reduce virus shedding in infected birds, and increase
the resistance to infection. Historically, one limitation of the killed vaccines is that vaccinated birds cannot be differentiated serologically from
naturally infected birds using the commonly available diagnostic tests. Therefore, surveillance for avian influenza becomes much more difficult
and often results in trade restrictions because of the inability to differentiate infected from vaccinated animals (DIVA). Several different DIVA
strategies have been proposed for avian influenza to overcome this limitation. The most common is the use of unvaccinated sentinels. A second
approach is the use of subunit vaccines targeted to the hemagglutinin protein that allows serologic surveillance to the internal proteins. A third
strategy is to vaccinate with a homologous hemagglutinin to the circulating field strain, but a heterologous neuraminidase subtype. Serologic
surveillance can then be performed for the homologous NA subtype as evidence of natural infection. The fourth strategy is to measure the se-
rologic response to the nonstructural protein 1 (NS1). The NS1 protein is produced in large quantities in infected cells, but it is not packaged in
the virion. Since killed vaccines for influenza are primarily made with whole virions, a differential antibody response can be seen between nat-
urally infected and vaccinated animals. However, poultry vaccines are not highly purified, and they contain small amounts of the NS1 protein.
Although vaccinated chickens will produce low levels of antibody to the NS1 protein, virus infected chickens will produce higher levels of NS1
antibody, and the two groups can be differentiated. All four DIVA strategies have advantages and disadvantages, and further testing is needed to
identify the best strategy to make vaccination a more viable option for avian influenza.
Published by Elsevier Ltd on behalf of The International Association for Biologicals.
Keywords: Avian influenza; Vaccination; DIVA; NS1; Hemagglutinin; Neuraminidase; Antigenic drift

DIVA Stragetien:
1. Sentinel birds
2. Subunit vaccines: d.h. Vaccinen, die im wesentlichen nur HA und NA AG enthalten, auch Vektorvaccinen.
3. Heterologe NA Strategie
4. NS 1 Diva Stragtegie

Avian Pathol. 2003 Aug;32(4):335-43.Links
The use of vaccination as an option for the control of avian influenza.Capua I, Marangon S.
Office International des Epizooties and National Reference Laboratory for Newcastle Disease and Avian Influenza, Istituto Zooprofilattico Sperimentale delle Venezie, Via Romea 14/A, 35020 Legnaro (PD), Italy, icapua@izsvenezie.it

Recent epidemics of highly contagious animal diseases included in list A of the Office International des Epizooties, such as foot-and-mouth disease, classical swine fever and avian influenza (AI), have led to the implementation of stamping-out policies resulting in the depopulation of millions of animals. The enforcement of a control strategy based on culling animals that are infected, suspected of being infected or suspected of being contaminated, which is based only on the application of sanitary restrictions on farms, may not be sufficient to avoid the spread of infection, particularly in areas that have high animal densities, thus resulting in mass depopulation. In the European Union, the directive that imposes the enforcement of a stamping-out policy (92/ 40/EC) for AI was adopted in 1992 but was drafted in the 1980s. The poultry industry has undergone substantial changes in the past 20 years, mainly resulting in shorter production cycles and in higher animal densities per territorial unit. Due to these organizational changes, infectious diseases are significantly more difficult to control because of the greater number of susceptible animals reared per given unit of time and due to the difficulties in applying adequate biosecurity measures. The slaughter and destruction of great numbers of animals is also questionable from an ethical point of view. For this reason, mass depopulation has raised serious concerns for the general public and has recently led to very high costs and economic losses for national and federal governments, stakeholders and, ultimately, for consumers. In the past, the use of vaccines in such emergencies has been limited by the impossibility of differentiating vaccinated/infected from vaccinated/non-infected animals. The major concern was that through trade or movement of apparently uninfected animals or products, the disease could spread further or might be exported to other countries. For this reason, export bans have been imposed on countries enforcing a vaccination policy. This review considers the possible strategies for the control of avian influenza infections, bearing in mind the new proposed definition of AI, including the advantages and disadvantages of using conventional inactivated (homologous and heterologous) vaccines and recombinant vaccines. Reference is made to the different control strategies, including the restriction measures to be applied in case of the enforcement of a vaccination policy. In addition, the implications of a vaccination policy on trade are discussed. It is concluded that if vaccination is accepted as an option for the control of AI, vaccine banks, including companion diagnostic tests, must be established and made available for immediate use.

PMID: 17585456 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/sites/en...ubmed_RVDocSum

Effects of homologous and heterologous neuraminidase vaccines in chickens against H5N1 highly pathogenic avian influenza.

Lee YJ, Sung HW, Choi JG, Lee EK, Jeong OM, Kwon YK, Kwon JH, Song CS, Kimd JH.
Avian Dis. 2007 Mar;51(1 Suppl):476-8.
Avian Disease Division, National Veterinary Research and Quarantine Service, Ministry of Agriculture and Forestry, 480 Anyang 6-dong, Anyang, Gyeonggi-do 430-016, Korea.

http://www.ncbi.nlm.nih.gov/sites/en...ubmed_RVDocSum

The 2004 Asian H5N1 epizootic outbreak indicates the urgent need for vaccines against highly pathogenic avian influenza (HPAI) virus. The manufacture of inactivated whole-virus vaccines from HPAI viruses by traditional methods is not feasible for safety reasons as well as technical issues. The low pathogenic avian influenza A/wild bird feces/CSM2/02 (H5N3) virus was used as a heterologous neuraminidase vaccine, and HPAI A/CK/Korea/ES/03 (H5N1) virus was used as a homologous neuraminidase vaccine. Protection efficacy of both vaccines was evaluated by clinical signs, mortality rates, and virus shedding from oropharynx and cloaca of vaccinated chickens after challenge with HPAI A/CK/Korea/ES/03 (H5N1) virus. One dose of 128 hemagglutinin (HA) homologous H5N1 vaccine induced 100% protection in mortality and prevented viral shedding completely after lethal dose virus challenge, whereas one dose of 64 HA unit of heterologous H5N3 vaccine only induced 50% protection in mortality, and it did not prevent viral shedding. However, two doses at a 3-wk interval of 64 HA unit of heterologous H5N3 vaccine as well as one dose of 1024 HA unit of heterologous H5N3 vaccine induced 100% survival rate and could prevent viral shedding completely. Furthermore, we could differentiate the sera of infected birds from those of vaccinated birds by indirect immunofluorescent antibody test. These results suggest that heterologous neuraminidase H5N3 vaccine could be a useful tool for the control of H5N1 HPAI epidemic in poultry.

PMID: 17494612 [PubMed - indexed for MEDLINE]

Avian Dis. 2007 Mar ;51 (1 Suppl):498-500 17494618

Efficacy of a fowlpox-vectored avian influenza H5 vaccine against Asian H5N1 highly pathogenic avian influenza virus challenge.
[My paper] Michel Bublot , Nikki Pritchard , Julio S Cruz , Thomas R Mickle , Paul Selleck , David E Swayne
A recombinant fowlpox-avian influenza (AI) H5 vaccine (rFP-AIV-HS) expressing the hemagglutinin of the A/turkey/Ireland/1378/83 H5N8 AI isolate has been used in Central America since 1998 to control H5N2 low pathogenicity AI. Previously, this vaccine was shown to induce full protection against a panel of H5 highly pathogenic (HP) AI isolates, including HPAI H5N1. Here, we evaluate the efficacy of rFP-AIV-H5 against escalating doses of HPAI H5N1 A/chicken/ SouthKorea/ES/03 isolate and against the HPAI H5N1 A/chicken/Vietnam/0008/2004 isolate. In both studies, 1-day-old specific pathogen-free (SPF) chickens were vaccinated by subcutaneous route with rFP-AIV-H5 and challenged 3 wk later by the oronasal route. In the first study, full protection was observed up to a challenge dose of 6.5 log10 embryo infectious dose (EID50), and the 50% chicken infectious dose was estimated to be 3.1 and 8.5 log10 EID50 in the control and the rFP-AIV-H5-vaccinated group, respectively. A 2-4 log10 and > 4 log10 reduction of oral and cloacal shedding was observed in rFP-AIV-H5 vaccinated birds, respectively. The rFP-AIV-H5 vaccine induced hemagglutination inhibition antibodies (5.2 log2) detectable with homologous H5N8 antigen. In the second study, rFP-AIV-HS-vaccinated chicks were fully protected against morbidity and mortality after challenge with the 2004 Vietnam isolate, whereas unvaccinated chickens died within 2 days of challenge. Shedding in cloacal swabs was detected in all unvaccinated controls but in none of the rFP-AIV-H5-vaccinated chickens. Together, these results confirm the excellent level of protection induced by rFP-AIV-H5 in SPF chickens against two recent Asian HPAI H5N1 isolates