Cross-protection against influenza virus infection afforded by trivalent inactivated vaccines inoculated intranasally with cholera toxin B subunit.
Cross-protection against influenza virus infection was examined in mice, immunized intranasally with a nasal site-restricted volume of inactivated vaccines together with cholera toxin B subunit (CTB) as an adjuvant. The mice were challenged with either a small or a large volume of mouse-adapted virus suspension, each of which gave virgin mice either a predominant upper or lower respiratory tract infection. A single dose of a monovalent influenza A H3N2 virus vaccine with CTB provided complete cross-protection against the small-volume challenge with a drift virus within the same subtype, but a slight cross-protection against the large-volume challenge. A second dose of another drift virus vaccine increased the efficacy of cross-protection against the large-volume challenge. Similar cross-protection against H1N1, H3N2, or B type drift virus challenge was provided in the mice having received a primary dose of a mixture of H1N1, H3N2, and B virus vaccines with CTB and a second dose of another trivalent vaccine. The degree of cross-protection against the small- and the large-volume infection paralleled mainly the amount of cross-reacting IgA antibodies to challenge virus hemagglutinin in the nasal wash and that of cross-reacting IgG antibodies in the bronchoalveolar wash, respectively. On the other hand, in mice immunized subcutaneously with the trivalent vaccines having no cross-reacting IgA antibodies, the efficacy of cross-protection was not so high as that of nasal vaccination. These results suggest that the nasal inoculation of trivalent vaccines with CTB provides cross-protection against a broader range of viruses than does the current parenteral vaccination.
Tamura
S
S
Department of Pathology, National Institute of Health, Tokyo, Japan.
Ito
Y
Y
Asanuma
H
H
Hirabayashi
Y
Y
Suzuki
Y
Y
Nagamine
T
T
Aizawa
C
C
Kurata
T
T
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002772:Cholera Toxin / Q000276:immunology; D003429:Cross Reactions; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D002772:Cholera Toxin