Van Reeth Kristien, Gregory Vicki, Hay Alan, Pensaert Maurice
Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
Vaccine. 2003 Mar 28;21(13-14):1375-81. doi: 10.1016/s0264-410x(02)00688-6.
A novel swine influenza virus, H1N2, circulates in European swine populations together with H1N1 and H3N2 viruses. This study examines whether post-infection immunity to H1N1 and/or H3N2 viruses provides cross-protection against H1N2 infection. Pigs (n=51) were inoculated intranasally with either Sw/Belgium/1/98 (H1N1) or Sw/Flanders/1/98 (H3N2), or with both viruses at a 5-week interval. Control groups were left uninoculated or inoculated with Sw/Gent/7625/99 (H1N2). Four weeks later, all the pigs were challenged intranasally and intratracheally with a high H1N2 virus dose. The challenge control pigs showed typical influenza symptoms, and all had high H1N2 virus titres in the lungs and nasal virus excretion during 6 or 7 days. The H1N2-immune pigs showed total clinical and virological protection. Pigs immune against H1N1 or H3N2 only were not protected against disease and virus replication in the lungs, but virus excretion was 2 days shorter. By contrast, pigs immune against both H1N1 and H3N2 did not show disease and H1N2 virus replication was either undetectable or markedly reduced. Haemagglutination inhibition (HI) and virus neutralisation (VN) tests indicated that cross-protection against H1N2 was probably not mediated by antibodies against the haemagglutinin (HA). Antibodies inhibiting the neuraminidase (NA) of H1N2 were at minimal levels in H3N2 only-immune pigs, but they were consistently found in (H1N1+H3N2)-immune pigs. The immune response against the internal proteins, which are relatively conserved in H1N1, H3N2 and H1N2 viruses, may play a significant role in protection against H1N2. Given the severe challenge model used here, cross-protection against H1N2 could be more pronounced under natural conditions of infection.
一种新型猪流感病毒H1N2与H1N1和H3N2病毒一起在欧洲猪群中传播。本研究检测感染H1N1和/或H3N2病毒后的免疫力是否能提供针对H1N2感染的交叉保护。给51头猪经鼻接种Sw/比利时/1/98（H1N1）或Sw/佛兰德/1/98（H3N2），或间隔5周接种两种病毒。对照组不接种或接种Sw/根特/7625/99（H1N2）。4周后，所有猪经鼻和气管内接种高剂量H1N2病毒。攻毒对照猪表现出典型的流感症状，且在6或7天内肺中H1N2病毒滴度均高，并有鼻病毒排出。免疫H1N2的猪表现出完全的临床和病毒学保护。仅免疫H1N1或H3N2的猪不能抵御疾病，肺中病毒仍可复制，但病毒排出时间缩短2天。相比之下，同时免疫H1N1和H3N2的猪未出现疾病，且H1N2病毒复制要么检测不到，要么显著减少。血凝抑制（HI）和病毒中和（VN）试验表明，针对H1N2的交叉保护可能不是由抗血凝素（HA）抗体介导的。仅免疫H3N2的猪中抑制H1N2神经氨酸酶（NA）的抗体水平极低，但在同时免疫（H1N1+H3N2）的猪中始终能检测到。针对H1N1、H3N2和H1N2病毒中相对保守的内部蛋白的免疫反应可能在抵御H1N2中起重要作用。鉴于此处使用的是严重攻毒模型，在自然感染条件下针对H1N2的交叉保护可能更明显。
