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immunisation protects ferrets againts homologous and heterologous challenge

A

Anne

Senior Moderator
<dl><dt><table cellpadding="0" cellspacing="0" width="100%"><tbody><tr><td>J Infect Dis. 2006 Jul 15;194(2):159-67. Epub 2006 Jun 9.</td> <td align="right">Related Articles,<script language="JavaScript1.2"> <!-- var PopUpMenu2_LocalConfig_jsmenu3Config = [ ["ShowCloseIcon","yes"], ["Help","window.open('/entrez/query/static/popup.html','Links_Help','resizable=no,scrollbars=yes,toolbar=no,location=no,directories=no,status=no,menubar=no,copyhistory=no,alwaysRaised=no,depend=no,width=400,height=500');"], ["TitleText"," Links "] ] var jsmenu3Config = [ ["UseLocalConfig","jsmenu3Config","",""] ] //--> </script> <script language="JavaScript1.2"> <!-- var Menu16779721 = [ ["UseLocalConfig","jsmenu3Config","",""], ["Books","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=pubmed_Abstract&cmd=Retrieve&db=pubmed&list_uids=16779721&dopt=Books'","",""], ["LinkOut","window.top.location='http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=pubmed_Abstract&cmd=Retrieve&db=pubmed&list_uids=16779721&dopt=ExternalLink'","",""] ] //--> </script> Links </td> </tr></tbody></table></dt><dd>
Comment in: [SIZE=+1]Immunization with reverse-genetics-produced H5N1 influenza vaccine protects ferrets against homologous and heterologous challenge.[/SIZE]

Govorkova EA, Webby RJ, Humberd J, Seiler JP, Webster RG.

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.

BACKGROUND: Multiple cases of transmission of avian H5N1 influenza viruses to humans illustrate the urgent need for an efficacious, cross-protective vaccine. METHODS: Ferrets were immunized with inactivated whole-virus vaccine produced by reverse genetics with the hemagglutinin (HA) and neuraminidase genes of A/HK/213/03 virus. Ferrets received a single dose of vaccine (7 or 15 microg of HA) with aluminum hydroxide adjuvant or 2 doses (7 microg of HA each) without adjuvant and were challenged with 10(6) 50% egg infectious doses of A/HK/213/03, A/HK/156/97, or A/Vietnam/1203/04 virus. RESULTS: One or 2 doses of vaccine induced a protective antibody response to the vaccine strain. All immunization regimens completely protected ferrets from challenge with homologous wild-type A/HK/213/03 virus: no clinical signs of infection were observed, virus replication was significantly reduced (P<.05) and was restricted to the upper respiratory tract, and spread of virus to the brain was prevented. Importantly, all vaccinated ferrets were protected against lethal challenge with the highly pathogenic strain A/Vietnam/1203/04. The 2-dose schedule induced higher levels of antibodies that were cross-reactive to antigenically distinct H5N1 viruses. CONCLUSIONS: H5N1 vaccines may stimulate an immune response that is more cross-protective than what might be predicted by in vitro assays and, thus, hold potential for being stockpiled as "initial" pandemic vaccines.</dd></dl>anne : I have problems to understand the animal model.
The ferret seems better than the mouse?
In addition, I believed that there was no crossed immunity between differents clades.
some help..?
 
Re: immunisation protects ferrets againts homologous and heterologous challenge

Mingus - Can you get the full text?
 
Re: immunisation protects ferrets againts homologous and heterologous challenge

It will help to have the whole article :)
I really don't understand.
 
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Re: immunisation protects ferrets againts homologous and heterologous challenge

see also the WHO vaccine recommendation:

http://209.85.129.104/search?q=cache:-N_ZcWleONAJ:www.who.int/csr/disease/avian_influenza/guidelines/recommendationvaccine.pdf+who+a/turkey/15/2005&hl=de&gl=de&ct=clnk&cd=1&ie=UTF-8

there is some cross-protection.

Also, I remember we had discussed this some months ago, when the
result was in the media, that Vietnam/1203 showed good cross-preotection. Webster (or Fauci?) considered it encouraging.

VNM/1203 and HK/213 are not so much different.

nucleotide-differences in HA:


Code: 
[FONT=Fixedsys]number of differences in HA            01 02 03 04 05 06 07 08 09 10 11 12 13 14 15     sum tested
--------------------------------------------------------------------------------------------------
01 A/Viet Nam/1194/2004                -- 15 15 65 72 78 62 60 57 65 49 58 55 31 68     750  24582 
02 A/Viet Nam/1203/2004                15 -- 12 62 68 75 60 61 58 66 46 55 52 28 63     721  24582 
03 A/Thailand/16/2004                  15 12 -- 60 67 73 59 59 56 64 44 53 50 24 59     695  24582 
04 A/Indonesia/5/2005                  65 62 60 -- 07 57 59 64 59 65 54 60 57 58 79     806  24582 
05 A/Indonesia/CDC357/2006             72 68 67 07 -- 62 66 71 66 72 61 67 64 65 85     893  24582 
06 A/Indonesia/CDC625/2006             78 75 73 57 62 -- 71 76 71 77 64 70 69 69 90    1002  24582 
07 ISDN133105 A/Turkey/15/2006         62 60 59 59 66 71 -- 15 16 14 49 57 54 53 76     711  24582 
08 A/Whooping swan/Mongolia/244/2005   60 61 59 64 71 76 15 -- 07 17 52 59 56 55 80     732  24435 
09 A/Bar headed goose/Qinghai/1A/2005  57 58 56 59 66 71 16 07 -- 18 47 52 51 50 75     683  24435 
10 A/turkey/Turkey/1/2005              65 66 64 65 72 77 14 17 18 -- 54 62 59 56 81     770  24582 
11 A/Duck/Hunan/15/2004                49 46 44 54 61 64 49 52 47 54 -- 25 24 38 62     669  24552 
12 A/Anhui/1/2005                      58 55 53 60 67 70 57 59 52 62 25 -- 11 49 74     752  24552 
13 A/Guangxi/1/2005                    55 52 50 57 64 69 54 56 51 59 24 11 -- 48 73     723  24552 
14 A/Hong Kong/213/2003                31 28 24 58 65 69 53 55 50 56 38 49 48 -- 58     682  24582 
15 A/HongKong/156/97(H5N1)             68 63 59 79 85 90 76 80 75 81 62 74 73 58 --    1023  24582 
[/FONT]
 
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Re: immunisation protects ferrets againts homologous and heterologous challenge

thanks, Mingus :)
 
Re: immunisation protects ferrets againts homologous and heterologous challenge

there is one paragraph about the T-cell immunity:

-----------------------
However, it<SUP> </SUP>seems more likely that<SUP> </SUP>T cell responses to<SUP> </SUP>internal proteins of the<SUP> </SUP>H3N2 viruses would not<SUP> </SUP>influence protection, because these<SUP> </SUP>proteins are genetically distinct<SUP> </SUP>from those of H5N1<SUP> </SUP>viruses [34]. Cytotoxic T<SUP> </SUP>lymphocytes (CTLs) play an<SUP> </SUP>important role in the<SUP> </SUP>control of influenza infection<SUP> </SUP>[35]. Alternatively, H5N1-specific CTLs<SUP> </SUP>may have been induced<SUP> </SUP>by vaccination. However, the<SUP> </SUP>extent and significance of<SUP> </SUP>previous cellular immunity in<SUP> </SUP>the protection of ferrets<SUP> </SUP>in our experiments is<SUP> </SUP>unknown, and H3-seropositive control<SUP> </SUP>ferrets were highly susceptible<SUP> </SUP>to infection and disease<SUP> </SUP>with A/Vietnam/1203/04 virus. Although<SUP> </SUP>intramuscular vaccination with an<SUP> </SUP>inactivated influenza vaccine induces<SUP> </SUP>little CTL stimulation in<SUP> </SUP>humans [36], little is<SUP> </SUP>known about the cellular<SUP> </SUP>response in ferrets and<SUP> </SUP>the potential contribution of<SUP> </SUP>cross-priming of antigen-specific CTLs<SUP> </SUP>[37, 38].<SUP> </SUP>
-----------------------

so, you wonder why they didn't use the whole HK/213 virus
but the internal genes from PR/8/34.
Or in the prepandemic Vaccine the whole VNM/1203
(with S227N mutation) and then give it as a spray like flumist.
Presumably it's more difficult and expensive
 
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