成人のインフルエンザウイルス特異的鼻腔分泌型IgA抗体価と血清IgG抗体価の保有状況とワクチン接種による影響

インフルエンザウイルスに対するヒトの粘膜免疫と全身免疫を検討した. 155名の健常成人を対象に, 鼻腔分泌液中のインフルエンザウイルス特異的 IgA 抗体と血液中のインフルエンザウイルス特異的 IgG 抗体の抗体価を測定したところ, 鼻腔の抗体保有率は約70%で, 血液中の抗体保有率はほぼ100%だった. インフルエンザワクチンが鼻腔および血液中の抗体価に及ぼす影響を調査するため, 初回の検体採取直後にワクチン接種し, その1カ月後に改めて検体採取して抗体価の変動を調査したところ, インフルエンザワクチン接種1カ月後に鼻腔のインフルエンザウイルス特異的 IgA 抗体価は上昇せず, 血液中のインフルエンザウイルス特異的 IgG 抗体価は上昇した. サブグループ解析では, 血液中の抗体価が低い場合に抗体価は上昇し, 高い場合は上昇せず, 頭打ち現象が見られた. インフルエンザワクチンは血液中の IgG 抗体価を上昇させ重症化を防ぐ一方, 鼻腔の分泌型 IgA 抗体を上昇させないため感染を防御する効果が乏しいと考えられた. また以前報告したインフルエンザ感染患者の鼻腔・血液中の抗体価と本研究の結果を比較検討したところ, 健常成人の保有する抗体価は鼻腔・血液中とも低い値から高い値まで幅広く分布していたのに対し, 感染患者の保有する鼻腔・血液中の抗体価は低かった. 鼻腔に保有する抗体価が低い例では高い例に比べ感染のリスクが高まる可能性がある.

In order to clarify human mucosal and systemic immunity against influenza viral infection, the serum titers of anti-influenza virus-specific nasal secretory IgA and serum IgG and their changes after subcutaneous vaccination were measured in a Japanese healthy adult population in the present study. We recruited 155 healthy adults in 2006, with an average age of 24.1 years (range: 19-60 years). The male-female ratio was 1: 1. Nasopharyngeal lavage fluid and serum specimens were obtained prior to vaccination and a month after subcutaneous vaccination with a trivalent influenza ether split hemagglutinin vaccine of the A (H1N1), A (H3N2) subtypes and type B influenza viruses. Nasopharyngeal lavage fluid specimens were obtained by the nasal spray and aspiration method. The anti-influenza virus-specific IgA titers in the nasopharyngeal lavage fluid and IgG titers in the serum against the A (H1N1), A (H3N2) subtype and type B influenza viruses were measured by ELISA. The anti-influenza virus-specific nasal lavage fluid IgA titers were represented as a ratio to the total IgA titers. About 70% of the subjects had nasal anti-viral IgA against the A (H1N1), A (H3N2) subtype and type B influenza viruses, and almost all had serum anti-viral IgG against the A (H1N1), A (H3N2) subtype and type B viruses. The serum antiviral IgG titers, but not the nasal antiviral IgA titers, were significantly elevated at 1 month after the subcutaneous vaccination. Moreover, the serum antiviral IgG titers were significantly elevated after vaccination only in subjects with low pre-vaccination IgG titers, and not in those with high pre-vaccination IgG titers. The nasal antiviral IgA titers in the subjects of our present study were significantly higher than those in patients with influenza infection reported from our previous study. The presence of nasal anti-influenza virus-specific IgA in about 70% of Japanese adults is considered as being suggestive of a history of influenza infection. The presence of anti-influenza virus-specific IgG in the serum in almost all Japanese adults could suggest a history of influenza infection or influenza vaccination. Currently available subcutaneous influenza vaccines induce systemic immunity, with the appearance of anti-viral IgG in the serum, in adults. However, subcutaneous vaccination does not appear to be capable of inducing mucosal immunity with the induction of antiviral secretory IgA in the nasopharynx. The present findings suggest that subcutaneous influenza vaccination can suppress the progression of influenza infection by inducing the appearance of antiviral IgG in serum, but not by inducing the appearance of antiviral IgA in the nasopharynx. The findings also suggest that subjects with low antiviral secretory IgA titers in the nasopharynx are at a higher risk of influenza infection.