Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
J Virol. 2013 Jul;87(14):7793-804. doi: 10.1128/JVI.00979-13. Epub 2013 May 22.
A serum hemagglutination inhibition (HAI) titer of 40 or greater is thought to be associated with reduced influenza virus pathogenesis in humans and is often used as a correlate of protection in influenza vaccine studies. We have previously demonstrated that intramuscular vaccination of guinea pigs with inactivated influenza virus generates HAI titers greater than 300 but does not protect vaccinated animals from becoming infected with influenza virus by transmission from an infected cage mate. Only guinea pigs intranasally inoculated with a live influenza virus or a live attenuated virus vaccine, prior to challenge, were protected from transmission (A. C. Lowen et al., J. Virol. 83:2803-2818, 2009.). Because the serum HAI titer is mostly determined by IgG content, these results led us to speculate that prevention of viral transmission may require IgA antibodies or cellular immune responses. To evaluate this hypothesis, guinea pigs and ferrets were administered a potent, neutralizing mouse IgG monoclonal antibody, 30D1 (Ms 30D1 IgG), against the A/California/04/2009 (H1N1) virus hemagglutinin and exposed to respiratory droplets from animals infected with this virus. Even though HAI titers were greater than 160 1 day postadministration, Ms 30D1 IgG did not prevent airborne transmission to passively immunized recipient animals. In contrast, intramuscular administration of recombinant 30D1 IgA (Ms 30D1 IgA) prevented transmission to 88% of recipient guinea pigs, and Ms 30D1 IgA was detected in animal nasal washes. Ms 30D1 IgG administered intranasally also prevented transmission, suggesting the importance of mucosal immunity in preventing influenza virus transmission. Collectively, our data indicate that IgG antibodies may prevent pathogenesis associated with influenza virus infection but do not protect from virus infection by airborne transmission, while IgA antibodies are more important for preventing transmission of influenza viruses.
血清血凝抑制（HAI）滴度达到 40 或更高被认为与人类流感病毒发病机制降低相关，并且常用于流感疫苗研究中的保护相关性。我们之前已经证明，用灭活流感病毒对豚鼠进行肌肉内接种会产生大于 300 的 HAI 滴度，但不能保护接种动物免受感染笼伴感染的流感病毒。只有在挑战之前用活流感病毒或活减毒病毒疫苗对豚鼠进行鼻内接种，才能防止传播（A. C. Lowen 等人，J. Virol. 83:2803-2818, 2009.）。因为血清 HAI 滴度主要由 IgG 含量决定，这些结果使我们推测预防病毒传播可能需要 IgA 抗体或细胞免疫反应。为了评估这一假说，豚鼠和雪貂接受了针对 A/加利福尼亚/04/2009（H1N1）病毒血凝素的强效中和性鼠 IgG 单克隆抗体 30D1（Ms 30D1 IgG）的给药，并暴露于来自感染这种病毒的动物的呼吸道飞沫中。尽管 HAI 滴度在给药后 1 天大于 160，但 Ms 30D1 IgG 并不能阻止被动免疫的接受动物空气中的传播。相比之下，肌肉内给予重组 30D1 IgA（Ms 30D1 IgA）可防止 88%的接受豚鼠传播，并且在动物鼻洗液中检测到 Ms 30D1 IgA。鼻内给予 Ms 30D1 IgG 也可阻止传播，这表明黏膜免疫在预防流感病毒传播中很重要。总的来说，我们的数据表明 IgG 抗体可能预防与流感病毒感染相关的发病机制，但不能防止通过空气传播的病毒感染，而 IgA 抗体对于预防流感病毒的传播更为重要。
