Tamura S, Ito Y, Asanuma H, Hirabayashi Y, Suzuki Y, Nagamine T, Aizawa C, Kurata T
Department of Pathology, National Institute of Health, Tokyo, Japan.
J Immunol. 1992 Aug 1;149(3):981-8.
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.
在小鼠中检测了针对流感病毒感染的交叉保护作用，这些小鼠经鼻内接种了鼻腔部位受限体积的灭活疫苗，并添加霍乱毒素B亚基（CTB）作为佐剂。用少量或大量适应小鼠的病毒悬液对小鼠进行攻击，每种病毒悬液都会使未感染过的小鼠分别发生主要在上呼吸道或下呼吸道的感染。单剂量含CTB的单价甲型H3N2流感病毒疫苗对同一亚型内的变异病毒小剂量攻击提供了完全交叉保护，但对大剂量攻击提供了轻微交叉保护。第二剂另一种变异病毒疫苗提高了对大剂量攻击的交叉保护效力。在接受了第一剂含CTB的H1N1、H3N2和B病毒疫苗混合物以及第二剂另一种三价疫苗的小鼠中，观察到了针对H1N1、H3N2或B型变异病毒攻击的类似交叉保护作用。针对小剂量和大剂量感染的交叉保护程度分别主要与鼻洗液中针对攻击病毒血凝素的交叉反应性IgA抗体量以及支气管肺泡洗液中交叉反应性IgG抗体量平行。另一方面，在皮下接种无交叉反应性IgA抗体的三价疫苗的小鼠中，交叉保护效力不如鼻内接种高。这些结果表明，与目前的肌内接种疫苗相比，经鼻接种含CTB的三价疫苗能提供更广泛的病毒交叉保护。
