Effect of immunomodulator adamantylamide dipeptide on antibody response to influenza subunit vaccines and protection against aerosol influenza infection.
Adamantylamide dipeptide (AdDP) is a novel synthetic compound combining the antiviral properties of amantadine and the essential adjuvant activity of immunomodulator muramyl dipeptide. Mice were immunized with influenza A/Taiwan/1/86 (H1N1), A/Sichuan/2/87 (H3N2) and influenza B/Beijing/1/87 subunit vaccines containing AdDP or aluminium hydroxide (Al(OH)3). Induction of homologous haemagglutination-inhibition (HI) antibodies and correlation to protection against lethal aerosol influenza A/PR/8/34 (H1N1) infection were investigated. Subunit vaccine containing A/Sichuan (H3N2) and Al(OH)3 stimulated high HI antibody titres but failed to provide protection against heterologous influenza A (H1N1) challenge infection following either the primary or the secondary immunizations. In contrast, similar treatment with A/Sichuan subunit vaccine containing AdDP conferred significant protection against heterologous challenge despite low levels of circulating antibody. Primary immunization with even influenza B/Beijing subunit vaccine containing AdDP, but not Al(OH)3, provided partial protection against influenza A challenge. These results suggest that appropriate immunomodulators like AdDP can convert restricted homotypic immunity induced by inactivated influenza subunit vaccines to advantageous cross-reacting type of heterologous response.
Masihi
K N
KN
Robert Koch Institute, Federal Health Office, Berlin, FRG.
Lange
W
W
Schwenke
S
S
Gast
G
G
Huchshorn
P
P
Palache
A
A
Masek
K
K
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000336:Aerosols; D000536:Aluminum Hydroxide / Q000494:pharmacology; D000547:Amantadine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D003429:Cross Reactions; D004151:Dipeptides / Q000494:pharmacology*; D005260:Female; D006385:Hemagglutination Inhibition Tests; D009980:Influenza A virus / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000336:Aerosols; D000914:Antibodies, Viral; D004151:Dipeptides; D007252:Influenza Vaccines; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D000536:Aluminum Hydroxide; C044891:adamantylamide-alanyl-isoglutamine; D000547:Amantadine