経鼻インフルエンザウイルス蛋白質(あるいはプラスミドDNA)ワクチンの開発に伴う問題点

抄録

Natural influenza virus infection has been shown to be superior to current viral protein vaccines, which are administered subcutaneously to induce serum antiviral IgG antibodies (Abs), for inducing cross-protection against variant virus infection. The cross-protection induced by natural infection seems to be largely due to the induction of cross-reacting IgA Abs in the upper respiratory tract. This fact suggests that the development of immunization procedures to stimulate mucosal IgA production would improve the protective efficacy of viral DNA vaccines, as well as protein vaccines. To stimulate the IgA production, the protein vaccine together with cholera toxin or Escherichia coli heat-labile enterotoxin as an adjuvant were administered intranasally into BALB/c mice. The vaccination provided cross-protection against variant viruses, in parallel with the production of cross-reacting IgA Abs. Next, field trials were conducted to evaluate the efficacy of the nasal vaccine. The adjuvant-combined vaccine could induce both IgA and IgG responses higher than do the vaccine alone, with the prevention of influenza. Although no serious adverse effects were observed in the human trials, further studies will be required to reduce the toxicity and the allergenicity of these toxin adjuvant. New non-proteinous adjuvants, which may be better than the toxin adjuvant, remain to be developed. To develop effective DNA vaccines, plasmid DNAs encoding hemagglutinin (HA), neuraminidase (NA). matrix protein, nucleoprotein and nonstructural protein from the virus were immunized in mice by particle-mediated DNA transfer to the epidermis (gene gun).The viral surface glycoprotein (HA and NA)-expressing DNAs were most protective among the five DNAs. However, the DNA vaccine failed to provide cross-protection against variant viruses without inducing IgA Abs. Thus, the protective efficacy of the DNA vaccine would be improved by the DNA transfer to the mucosal epithelial cells, whose procedure remains to be developed.