Long- and short-time immunological memory in different strains of mice given nasally an adjuvant-combined nasal influenza vaccine.
ABSTRACT Immunological memory induced by nasal immunization with adjuvant-combined influenza vaccine was analyzed in different ages and strains of mice. The memory activities were assessed by secondary nasal-wash IgA and serum IgG antibody (Ab) responses and protection against challenge infection with a lethal dose of influenza virus. Mice were primed with 0.1 microg of vaccine and boosted with 0.1 or 1.0 microg vaccine 1 (short-term memory)- or 17 (long-term memory)-months later. Influenza-specific short-term memory responses in young adult BALB/c mice (2-month-old) were significantly higher than those of long-term memory activities in mice boosted at 19 months of age. However, those influenza-specific long-term memory responses provided protective immunity against influenza virus challenge and were higher than short-term memory in aged mice primed at 18-month-old and boosted 1 month later. These results show that the age at which initial nasal immunization is given is critically important in order to induce protective immunity in aged mice. Similar findings were noted in the C3H mouse strain; however, C57BL/6 mice failed to induce influenza-specific immune responses in both young adult and aged mice. These results indicate that low doses of cholera toxin B subunit (supplemented with 0.2% of hole toxin) combined nasal vaccine may required further improvement in order to provide protective immunity in human use.
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Article: Options for the Control of Influenza01/1986;
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ABSTRACT: Evaluation of the efficacy of nasal influenza vaccine combined with Escherichia coli heat-labile enterotoxin B subunit (LTB) containing a trace amount of the holotoxin (LT) in inducing antibody responses among volunteers, which was conducted during the winter season of 1993-1994, is reported. A trivalent inactivated vaccine, composed of A/Yamagata/32/89 (H1N1), A/Kitakyusyu/159/93 (H3N2) and B/Bangkok/163/90 influenza virus strains, was used alone or together with the adjuvant, recombinant LTB supplemented with 0.5% recombinant LT (LTB*). The volunteers were divided into two groups: 73 volunteers (mean age 35.0 +/- 12.0 years) inoculated intranasally (i.n.) with LTB*-combined vaccine and 49 volunteers (37.9 +/- 11.3) inoculated i.n. with the vaccine alone. Vaccination was done twice 4 weeks apart. Salivary secretory IgA and serum hemagglutination-inhibiting (HI) antibodies were measured before and 8 weeks after the primary vaccination. For the sake of convenience, more than a 1.4-fold rise in IgA antibody response (units of specific IgA antibody per microgram of total IgA) and a fourfold or greater rise in HI antibody titer after vaccination were regarded as a positive antibody response. Thirty-seven (50.3%) and 36 (49.3%) of the 73 vaccinees, respectively, given the nasal LTB*-combined vaccine showed positive IgA and HI antibody responses to one or more of the three vaccine strains. In comparison, positive antibody responses in the group given vaccine alone were 32.7% for IgA and 30.6% for HI antibody. There was a significant difference between these two groups. These results suggest that the nasal LTB*-combined vaccine could enhance the production of higher levels not only of serum HI antibody but IgA antibodies in the respiratory tract than do the nasal vaccine alone.Vaccine 03/1996; 14(2):113-9. · 3.49 Impact Factor
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ABSTRACT: Immune responses and protection against influenza virus infection were compared between young (2 months) and aged (18 months) BALB/c, C3H and C57BL/6 (B6) mice after intranasal vaccination. The mice were immunized with 2.5 microg protein of A/PR/8/34 (PR8) (H1N1) virus vaccine containing a cholera toxin adjuvant. In both the young and aged BALB/c mice, high levels of PR8-specific antibody-forming cell (AFC) responses were induced in the nasal-associated lymphoid tissue (NALT) 7 days after immunization. Nasal wash IgA and serum IgG antibody (Ab) responses to the PR8 haemagglutinin (HA) 4 weeks after immunization were slightly higher in the young mice than in the aged mice. The young mice showed complete protection against challenge infection, while the aged mice showed only a partial protection. In the C3H mice, NALT-AFC, and IgA and IgG Ab responses were higher in the young mice than those in the aged mice in parallel with the more efficient protection in the young mice than in the aged mice. Both the young and aged B6 mice showed no NALT-AFC responses, scarce IgA and IgG Ab responses and no protection. In the BALB/c mice, IgG1 and IgG2a levels were significantly lower in the aged mice. On the other hand, in the C3H mice, only IgG2a level was significantly lower in the aged mice. Similar results were obtained in terms of immune responses and protection between the young and aged mice of three different strains of mice after intra-nasal immunization with 0.1 microg of PR8 vaccine containing the adjuvant, two-times at 4-week intervals. In the B6 mice, the immune response was improved by immunization with a higher dose of the adjuvant-combined vaccine. These results suggest that local Ab responses, as well as systemic Ab responses, are downregulated in aged mice, although the degree of the downregulation of immune responses differs from strain to strain.Vaccine 08/2001; 19(28-29):3981-9. · 3.49 Impact Factor