Intranasal immunization of Balb/c mice against prion protein attenuates orally acquired transmissible spongiform encephalopathy

被引:32
作者
Bade, S
Baier, M
Boetel, T
Frey, A
机构
[1] Res Ctr Borstel, D-23845 Borstel, Germany
[2] Robert Koch Inst, D-13353 Berlin, Germany
关键词
intranasal immunization; prions; secretory IgA;
D O I
10.1016/j.vaccine.2005.12.051
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
To test whether prion protein (PrP) specific secretory immunoglobulin A (slgA) can be induced and protect against oral transmission of spongiforin encephalopathy (SE) we immunized Balb/c mice either intragastrically or intranasally (i.n.) with a recombinant PrP-fragment (PrP90-231) and cholera toxin (CT) adjuvant. Since PrP90-231 was rapidly digested in intestinal lavage, aprotinin was added to some vaccine formulations. While an anti-CT response was elicited via both routes, solely i.n. immunization without aprotinin induced PrP-specific slgA. They recognize predominantly PrP-oligomers as the antigen was aggregated in the vaccine formulations. Challenge experiments showed that the immune response induced by Our protocol could not prevent disease, but increases the median survival of the animals. We conclude that PrP-specific slgA reduce the infectivity of the inoculum and that complete protection against transmission of SE should be achievable by optimized immunization regimens. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1242 / 1253
页数:12
相关论文
共 55 条
[1]   Early accumulation of PrPSc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie [J].
Andréoletti, O ;
Berthon, P ;
Marc, D ;
Sarradin, P ;
Grosclaude, J ;
van Keulen, L ;
Schelcher, F ;
Elsen, JM ;
Lantier, F .
JOURNAL OF GENERAL VIROLOGY, 2000, 81 :3115-3126
[2]   Prion diseases: infectious and lethal doses following oral challenge [J].
Baier, M ;
Norley, S ;
Schultz, J ;
Burwinkel, M ;
Schwarz, A ;
Riemer, C .
JOURNAL OF GENERAL VIROLOGY, 2003, 84 :1927-1929
[3]   Rapid prion neuroinvasion following tongue infection [J].
Bartz, JC ;
Kincaid, AE ;
Bessen, RA .
JOURNAL OF VIROLOGY, 2003, 77 (01) :583-591
[4]   Early accumulation of pathological PrP in the enteric nervous system and gut-associated lymphoid tissue of hamsters orally infected with scrapie [J].
Beekes, M ;
McBride, PA .
NEUROSCIENCE LETTERS, 2000, 278 (03) :181-184
[5]   Prion immunoreactivity in brain, tonsil, gastrointestinal epithelial cells, blood and lymph vessels in lemurian zoo primates with spongiform encephalopathy [J].
Bons, N ;
Mestre-Frances, N ;
Guiraud, I ;
Charnay, Y .
COMPTES RENDUS DE L ACADEMIE DES SCIENCES SERIE III-SCIENCES DE LA VIE-LIFE SCIENCES, 1997, 320 (12) :971-979
[6]   Natural and experimental oral infection of nonhuman primates by bovine spongiform encephalopathy agents [J].
Bons, N ;
Mestre-Frances, N ;
Belli, P ;
Cathala, F ;
Gajdusek, DC ;
Brown, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (07) :4046-4051
[7]   Transmissions to mice indicate that 'new variant' CJD is caused by the BSE agent [J].
Bruce, ME ;
Will, RG ;
Ironside, JW ;
McConnell, I ;
Drummond, D ;
Suttie, A ;
McCardle, L ;
Chree, A ;
Hope, J ;
Birkett, C ;
Cousens, S ;
Fraser, H ;
Bostock, CJ .
NATURE, 1997, 389 (6650) :498-501
[8]   MICE DEVOID OF PRP ARE RESISTANT TO SCRAPIE [J].
BUELER, H ;
AGUZZI, A ;
SAILER, A ;
GREINER, RA ;
AUTENRIED, P ;
AGUET, M ;
WEISSMANN, C .
CELL, 1993, 73 (07) :1339-1347
[9]  
Cantor C.R., 1980, BIOPHYSICAL CHEM PAR, P539
[10]  
Dalum I, 1996, J IMMUNOL, V157, P4796