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**Ganseerpel** · December 20, 2006, 04:28 AM

Re: Newcastle Live Vax Protects Against H5N1

<DIR><DIR>Protection of chickens against highly lethal H5N1 and H7N1 avian influenza viruses with a recombinant fowlpox virus co-expressing H5 haemagglutinin and N1 neuraminidase genes.

Protection of chickens against highly lethal H5N1 and H7N1 avian influenza viruses with a recombinant fowlpox virus co-expressing H5 haemagglutinin and N1 neuraminidase genes - PubMed

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12745375&dopt=Abstract

Inactivated whole avian influenza virus (AIV) vaccine provides protection against homologous haemagglutinin (HA) subtype virus, but poor protection against a heterologous HA virus. Moreover, it induces chickens to produce antibodies to cross-reactive antigens, especially nucleoprotein, which is limi …

Qiao CL, Yu KZ, Jiang YP, Jia YQ, Tian GB, Liu M, Deng GH, Wang XR, Meng QW, Tang XY.
Avian Pathol. 2003 Feb;32(1):25-32

</DIR></DIR>National Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences, P.R. China. QCHL2001@yahoo.com.cn

Inactivated whole avian influenza virus (AIV) vaccine provides protection against homologous haemagglutinin (HA) subtype virus, but poor protection against a heterologous HA virus. Moreover, it induces chickens to produce antibodies to cross-reactive antigens, especially nucleoprotein, which is limits AIV serological surveillance. In this study, a recombinant fowlpox virus co-expressing HA (H5 subtype) and NA (NI subtype)genes of AIV was evaluated for its ability to protect chickens against intramuscular challenge with a lethal dose of highly pathogenic (HP) AIV. Susceptible chickens were also vaccinated by wing-web puncture with the parent fowlpox vaccine virus. Following challenge 4 weeks later with HPAIV, all chickens vaccinated with recombinant virus were protected, while the chickens vaccinated with either the unaltered parent fowlpox vaccine virus or unvaccinated controls experienced 100% mortality following challenge. This protection was accompanied by the high levels of specific antibody to the respective components of the recombinant vaccine. The above results showed that rFPV-HA-NA could be a potential vaccine to replace current inactivated vaccines for preventing

**Ganseerpel** · December 20, 2006, 04:32 AM

Re: Newcastle Live Vax Protects Against H5N1

Clinical and Diagnostic Laboratory Immunology, November 2005, p. 1340-1342, Vol. 12, No. 11
1071-412X/05/$08.00+0 doi:10.1128/CDLI.12.11.1340-1342.2005
Copyright ? 2005, American Society for Microbiology. All Rights Reserved.
Immunogenicity of Fowlpox Virus Expressing the Avian Influenza Virus H5 Gene (TROVAC AIV-H5) in Cats

Kemal Karaca,1* David E. Swayne,2 Deborah Grosenbaugh,1 Michel Bublot,3 Amy Robles,1 Erica Spackman,2 and Robert Nordgren1
Merial Ltd., Athens, Georgia,1 Southeastern Poultry Research Laboratory, Athens, Georgia,2 Merial SAS, Lyon, France3
Received 2 June 2005/ Returned for modification 11 July 2005/ Accepted 5 August 2005 Vaccination of cats with fowlpox virus expressing the avian influenza (AI) virus H5 hemagglutinin gene (TROVAC AI) resulted in detectable hemagglutination inhibition (HI) antibody responses to the homologous A/Turkey/Ireland/1378/83 (H5N8) (A/tky/Ire/83) AI virus antigen. The HI antibody responses to heterologous A/Chicken/Indonesia/7/03 (H5N1) (A/ck/Indonesia/03) AI virus antigen were also detected in all vaccinated cats, but only after booster vaccinations. The vaccine described in this study and other poxvirus-vectored vaccines may be of value for the prophylaxis of AI virus-associated morbidity and mortality in mammals.

**Ganseerpel** · December 20, 2006, 04:40 AM

Re: Newcastle Live Vax Protects Against H5N1

Newcastle disease virus expressing H5 hemagglutinin gene protects chickens against Newcastle disease and avian influenza
Jutta Veits*, Dorothee Wiesner*, Walter Fuchs*, Bernd Hoffmann
?, Harald Granzow?, Elke Starick?, Egbert Mundt*, Horst Schirrmeier?, Teshome Mebatsion?, Thomas C. Mettenleiter*, and Angela Ro? mer-Oberdo? rfer*

Institutes of *Molecular Biology,
?Diagnostic Virology, and ?Infectology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health,
Boddenblick 5a, D-17493 Greifswald-Insel Riems, Germany; and ?Intervet, Inc., 29160 Intervet Lane, Millsboro, DE 19966
Communicated by Tilahun D. Yilma, University of California, Davis, CA, March 30, 2006 (received for review February 22, 2006)

Newcastle disease virus (NDV)-expressing avian influenza virus (AIV) hemagglutinin (HA) of subtype H5 was constructed by reverse genetics. A cloned full-length copy of the genome of the lentogenic NDV strain Clone 30 was used for insertion of the ORF encoding the HA of the highly pathogenic AIV isolate A chicken Italy 898 (H5N2) in the intergenic region between the NDV fusion and hemagglutinin-neuraminidase (HN) genes. Remarkably, two species of HA transcripts were detected in cells infected with the resultant NDVH5. In a second recombinant (NDVH5m), a NDV transcription termination signal-like sequence located within theHA ORF was eliminated by silent mutations. Consequently, NDVH5m produced 2.7-fold more full-length HA transcripts, expressed higher levels of HA, and also incorporated more HA protein into its envelope than NDVH5. NDVH5m stably expressed the modified HA gene for 10 egg passages and both recombinants were found innocuous after intracerebral inoculation of 1-day-old chickens. Immunization of chickens with NDVH5m induced NDVand AIVH5-specific antibodies and protected chickens against clinical disease after challenge with a lethal dose of velogenic NDV or highly pathogenic AIV, respectively. Remarkably, shedding of influenza virus was not observed. Furthermore, immunization with NDVH5m permitted serological discrimination of vaccinated and AIV field virus-infected animals based on antibodies against the nucleoprotein of AIV. Therefore, recombinant NDVH5m is suitable as a bivalent vaccine against NDV and AIV and may be used as marker vaccine for the control of avian influenza.

vaccine
recombinant Newcastle disease virus reverse genetics

**gsgs** · December 24, 2006, 04:50 AM

Re: Newcastle Live Vax Protects Against H5N1

no chance to find something similar for humans ?

there's lots of H5N1-chicken vaccine available, what happens when humans take it in a pandemic ?

**Ganseerpel** · December 24, 2006, 07:46 AM

Re: Newcastle Live Vax Protects Against H5N1

The ND virus is a bird adapted virus and does not replicate in normal human cells. Thus it is completely harmless and apathogen for humans - but on the other hand will not induce a sufficient immune response as required for a vaccine.

With one important exception: It replicates very efficiently in human tumor cell lines which leads to complete tumor destruction within a short time. One of the features is therapie of glioblastoma. ND is one of the most promising candidates among onkolytic viruses.

http://www.cancer.gov/cancertopics/p...thprofessional
http://www.koelner-modell.de/iozWeb/...ode1?pageid=55
http://www.egms.de/en/meetings/dgnc2...dgnc0121.shtml
http://www.nature.com/mt/journal/v13...mt200627a.html

One of the problems of life virus treatment in general is - once the mouse modell is adapted to humans - a rapidly developing immune response neutralizing more or less the viral agens (in contrast to mice). Furthermore non specific h?magglutination by host serum may occur

In AD virus vector vaccine technology this seems to be a minor relevance.

But the problem as such is imho not convincingly resolved.

**AlaskaDenise** · December 24, 2006, 09:19 AM

Re: Newcastle Live Vax Protects Against H5N1

How does NDV impact mentasticized cancer cells?

Since the study showed the disease returning for some patients, might it be due to distant mentastic cells?

.

**AlaskaDenise** · December 24, 2006, 09:23 AM

Re: Newcastle Live Vax Protects Against H5N1

Both a wild-type and a mutated HA open reading frame (ORF) from the HPAIV wild bird isolate, A/Bar-headed goose/Qinghai/3/2005 (H5N1), were inserted into the intergenic region between the P and M genes of the LaSota NDV vaccine strain.

How may this impact H5N1 mutations, as compared to regular poultry H5 VAX?

.

**Ganseerpel** · December 24, 2006, 09:56 AM

Re: Newcastle Live Vax Protects Against H5N1

How does NDV impact mentasticized cancer cells?

NDV has an innate selectivity for human tumor cells and replicates 10000 fold more in tumor cells than in normal human cells (leading to complete cell lysis). This has to do with the fact, that in tumor cells certain transduction pathways (indispensable for virus defense) are defective. Therefore viruses have a selective growth advantage in comparison with normal cells which supress virus growth.

Viro-therapy is not a new idea. Its roots could be found in the mid 20th Century, and several attempts have been made with herpes, AD virus and others.

<TABLE cellSpacing=0 cellPadding=6 width="100%" border=0><TBODY><TR><TD class=alt2 style="BORDER-RIGHT: 1px inset; BORDER-TOP: 1px inset; BORDER-LEFT: 1px inset; BORDER-BOTTOM: 1px inset">Both a wild-type and a mutated HA open reading frame (ORF) from the HPAIV wild bird isolate, A/Bar-headed goose/Qinghai/3/2005 (H5N1), were inserted into the intergenic region between the P and M genes of the LaSota NDV vaccine strain. </TD></TR></TBODY></TABLE>
How may this impact H5N1 mutations, as compared to regular poultry H5 VAX?

The ORF of the H5 strian is inserted into the genome of the NDV and afterwards expressed on its surface and on the surface of infected, AG presenting cells etc.

The impact on mutations is not significant as no influenza strain is involved in the vaccine/system. The risk of a potential mutation in the NDV genes is believed to be low.

**AlaskaDenise** · December 24, 2006, 10:00 AM

Re: Newcastle Live Vax Protects Against H5N1

...tumor cells certain transduction pathways (indispensable for virus defense) are defective.

So mentastic cells also have these defective pathways?

.

**AlaskaDenise** · December 24, 2006, 10:06 AM

Re: Newcastle Live Vax Protects Against H5N1

Viro-therapy is not a new idea. Its roots could be found in the mid 20th Century, and several attempts have been made with herpes, AD virus and others.

Does this mean that natural infection with some viruses can confer immunity to some cancer types?

I remember that TB patients cannot get some diseases - this may be a similar situation.

.

**AlaskaDenise** · December 24, 2006, 10:12 AM

Re: Newcastle Live Vax Protects Against H5N1

Perhaps I have my conclusions backwards, i.e., infection with certain virus may eventually allow certain cancers, as in agressive HPV strains.

.

**Ganseerpel** · December 24, 2006, 11:05 AM

Re: Newcastle Live Vax Protects Against H5N1

Does this mean that natural infection with some viruses can confer immunity to some cancer types?

This was the first experience leading to the idea that there could be a selective affinity to tumor cells. But I don't think that we can speak of an immunity confered by some viruses on a general level at present. Virus infections may have a positive effect on tumoral diseases in some cases - not more.

Viro-therapy is not a new idea. Its roots could be found in the mid 20th Century, when a number of physicians noticed an interesting phenomenon: some of their patients, who suffered from cancer and had an incidental viral infection, or subjected to vaccination, were now improving, experiencing a remission from their symptoms. In the 40s and 50s, studies were conducted in animal models to evaluate the use of viruses in the treatment of tumors, and in 1956, one of the first human clinical trials with an oncolytic virus was conducted in patients with advanced-stage cervical cancer. Nevertheless, systematic research of this field was delayed for years, due to lack of more advanced technologies. In recent years the research in the field of oncolytic viruses began to move forward more quickly. Last year it was reported that researchers from the Ohio State University Medical Center have been trying to use a genetically engineered herpes virus against one type of brain tumor in mice. The Ohio State researchers have modified one of the herpes genes so it will be active only in cells that made a protein called nestin. The results of the mice research were encouraging and some of the mice who received the treatment lived a few days more than the control group who did not receive the treatment.
source: http://www.isracast.com/Articles/Article.aspx?ID=15

Perhaps I have my conclusions backwards, i.e., infection with certain virus may eventually allow certain cancers, as in agressive HPV strains.

Many viruses that can persist for a long time in the organism are suspicioned or proven to have cancerogenous effects. HPV is shown to be the causative agent in cervix Ca genesis and the newly approved HPV vaccine is believed to confer protection.

But also this new vaccine is administered i.m. As we have increasing evidence that the way of administration is crucial because it determines the way of Ab-induction. IgA has been shown to play a dominant role in the defence and prevention of urinary tract infections - and perhaps does also in flu.

This fact has not been taken into account. And in HPV the main question has not been answered: What happens to the millions already infected? The results in infected patients are hitherto not promising.

**AlaskaDenise** · December 24, 2006, 09:35 PM

Re: Newcastle Live Vax Protects Against H5N1

M. G?nseerpel...

Are there other likely viral candidates more appropriate to humans?

Could AI be combined with something as common as a Coronavirus, as was tried for Rinderpest?

.

**Ganseerpel** · December 26, 2006, 11:58 AM

Re: Newcastle Live Vax Protects Against H5N1

Are there other likely viral candidates more appropriate to humans?<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /><o:p></o:p>

Could AI be combined with something as common as a Coronavirus, as was tried for Rinderpest?

<o:p></o:p>
<o:p></o:p>
In vector vaccines the the specific gene of a virulent virus coding an AG which evokes an immune response for immunoprotective proteins is isolated and then inserted into the genome of a nonvirulent virusspecies which expresses the AG. <o:p></o:p>
<o:p></o:p>
If the vector virus is not able to replicate (not human adapteded virus) in the host, there risk is minor (no reversion to virulence) but the CMI response is weak. (=Small, limited amount of AG - similar to common split vaccines )<o:p></o:p>
<o:p></o:p>
If the vector virus is capable of replication (=human or human adapted vector virus) CMI and humoral Immune response is good. (= Infection of host), but there are some risks (see below)<o:p></o:p>
<o:p></o:p>
So the question is always how to induce "a bit" of infection (stronger immune response) on the one hand but not "too much" on the other hand (risk of disease, virus evolution, virulence shift etc.)<o:p></o:p>
<o:p></o:p>
What are the best candidates? <o:p></o:p>
<o:p></o:p>
Investigations are under way for viruses as different as <o:p></o:p>
Adeno virus (AD), (non eveloped ds DNA) <o:p></o:p>
http://www.tulane.edu/~dmsander/WWW/335/Adenoviruses.html<o:p></o:p>
http://www.cdc.gov/ncidod/dvrd/revb/respiratory/eadfeat.htm<o:p></o:p>
(Turkey-) Herpes, (ds DNA) http://www.dbc.uci.edu/~faculty/wagner/movieindex.html<o:p></o:p>
Infectious Laryngotracheitis (ILT) http://www.fli.bund.de/863.html<o:p></o:p>
Fowlpox, http://chi.ucsf.edu/vaccine/vaccines?page=vc-01-03 <o:p></o:p>
ND (single stranded RNA) http://chi.ucsf.edu/vaccine/vaccines?page=vc-01-03 <o:p></o:p>
<o:p></o:p>
Adenoviridae seem to be rather favorite candidates, they have a DNA genome which is known to be much more stable than in RNA viruses and a broad spectrum of species<o:p></o:p>
replicates in human cells<o:p></o:p>
<o:p></o:p>
http://jvi.asm.org/cgi/content/full/80/4/1959<o:p></o:p>
http://www.flutrackers.com/forum/showthread.php?t=8773<o:p></o:p>
<o:p></o:p>
The principal risks ? as in all live vaccines ? are:<o:p></o:p>
<o:p></o:p>
- Reversion to virulence of vaccine strains; <o:p></o:p>
<o:p></o:p>
- Disease in individuals with compromised immune systems; <o:p></o:p>
<o:p></o:p>
- Teratogenity, particularly if the vaccine is adminsrered in the first trimester; <o:p></o:p>
<o:p></o:p>
- Infection unvaccinated persons by vaccine strains<o:p></o:p>
<o:p></o:p>
- Occurence of new, previously unknown complications.<o:p></o:p>
<o:p></o:p>
PS: Sorry not all the links are in english<o:p></o:p>
<o:p></o:p>

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Newcastle Live Vax Protects Against H5N1

Newcastle Live Vax Protects Against H5N1

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