Studies on the Development of Spray Influenza Vaccine Combined with an Adjuvant

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Effects of intransal inoculation of influenza HA vaccine, together with cholera toxin B subunit (CTB), on antibody responses to virus antigens and on protection against viral challenge were investigated in Balb/c mice.(1) The vaccine inoculated with CTB induced high responses of both antiviral IgA antibodies in the nasal wash and haemagglutinin-inhibiting (HI) antibody in the serum, enough to provide complete protection against viral challenge 4 weeks after immunization. (2) High levels of antibody were maintained for more than 16 weeks after inoculation, affording complete protection during this interval. (3) The inoculation of HA vaccine prepared from a variant virus within the same subtype or a different subtype virus, together with CTB, provided partial protection against viral infection, with production of antiviral cross-reacting IgA antibodies. (4) The two-dose regimen, composed of a primary internasal inoculation of vaccine together with CTB and the subsequent inoculation of va … More ccine alone 4 weeks later, induced much higher responses of both antiviral IgA antibodies in nasal wash and HI antibody in serum, which persisted for more than 12 weeks after the second inoculation. This regimen provided not only complete protection against homologous virus infection, but also partial cross-protection against heterologous A-type virus infection, in parallel with high persistent levels of cross-reacting IgA antibodies.Intranasal inoculation of haemagglutinin (HA) molecules, purified from virus, together with CTB into mice resulted in complete protection against viral infection in parallel with the induction of high levels of HA-specific IgA-specific IgA and IgG antibodies on the respiratory tract. The respiratory tract IgA, purified from nasal and lung washings, included cross-reacting antibodies besides specific antibodies, which were not only higher in content in the nasal wash, but also more cross-reactive than IgG. When passively transferred to normal mouse before infection, the purified IgA protected against viral challenge.These results suggest that intranasal vaccination of CTB-combined influenza inactivated vaccine or HA molecules, which consists of different subtype viruses and different type viruses, is very useful for controlling the outbreaks of influenza by inducing locsl IgA antibodies. Less