抗体中和病毒
Virus neutralization by antibodies


抗体反应对于预防许多病毒感染是至关重要的,也可能有助于感染的消除。当脊椎动物被病毒感染时,会产生针对多种病毒蛋白质上的抗原决定基 (epitope)的抗体。这些抗体的一个子集可以通过一个被称为中和的过程阻止病毒感染。


抗体可以以多种方式中和病毒的感染性,如插图所示。它们可能干扰病毒粒子与受体的结合,阻碍对细胞的吸收,阻止内吞体基因组的脱壳,或引起病毒粒子的聚集(Agregation)。当抗病毒抗体和血清补体破坏细胞膜时,许多包膜病毒被溶解。


抗体中和

病毒感染后也会产生非中和抗体。这种抗体专门与病毒颗粒结合,但不能消除传染性。它们可能增强传染性,因为抗体可以与巨噬细胞上的受体相互作用。整个病毒抗体复合物通过内吞(Endocyosis)作用进入细胞。病毒复制可以继续进行,因为抗体不能阻止传染性。这种途径可能允许进入通常不携带特定病毒受体的细胞。


抗体中和病毒在体内的什么地方发生?感染黏膜表面的病毒粒子会遇到上皮细胞顶端分泌的IgA抗体。在血液中传播的病毒将接触到IgG和IgM抗体。事实上,产生的抗体类型会影响病毒感染的结果。脊髓灰质炎病毒感染引起血液中IgM和IgG反应,但粘膜IgA对阻断感染至关重要。这种抗体可以中和肠内的脊髓灰质炎病毒,肠内是原发感染的部位。减毒沙宾脊髓灰质炎活疫苗是有效的,因为它能引起强烈的粘膜IgA反应并提供肠道免疫。相比之下,注射脊髓灰质炎疫苗(Salk)不能产生肠道免疫,因此在预防脊髓灰质炎病毒在人群中的传播方面效果较差。


绝大多数流感疫苗是注射的,刺激IgG抗体的产生;它们是黏膜IgA抗体的不良诱导物。如果能够设计出能够刺激粘膜免疫的流感疫苗,其功效可能会显著提高。Flumist是一种经许可的鼻内注射的传染性病毒疫苗,已被证明能够刺激粘膜和全身免疫。在儿童中进行了九项临床试验,比较了氟雾药与灭活疫苗或安慰剂的疗效。结果分析表明,鼻内接种疫苗对预防流感更有效。这些结果强调了局部免疫在抵抗呼吸道病原体中的作用。

 

Virus neutralization by antibodies


The antibody response is crucial for preventing many viral infections and may also contribute to resolution of infection. When a vertebrate is infected with a virus, antibodies are produced against many epitopes on multiple virus proteins. A subset of these antibodies can block virus infection by a process that is called neutralization.

Antibodies can neutralize viral infectivity in a number of ways, as summarized in the illustration. They may interfere with virion binding to receptors, block uptake into cells, prevent uncoating of the genomes in endosomes, or cause aggregation of virus particles. Many enveloped viruses are lysed when antiviral antibodies and serum complement disrupt membranes.

antibody-neutralization

Non-neutralizing antibodies are also produced after viral infection. Such antibodies bind specifically to virus particles, but do not neutralize infectivity. They may enhance infectivity because antibodies can interact with receptors on macrophages. The entire virus-antibody complex is brought into the cell by endocytosis. Viral replication can then proceed because the antibody does not block infectivity. This pathway may allow entry into cells which normally do not bear specific virus receptors.

Where in the body does antibody neutralization of viruses take place? Virions that infect mucosal surfaces encounter secretory IgA antibodies present at the apical surfaces of epithelial cells. Viruses that spread in the blood will be exposed to IgG and IgM antibodies. In fact, the type of antibody that is produced can influence the outcome of viral infection. Infection with poliovirus causes IgM and IgG responses in the blood, but mucosal IgA is vital for blocking infection. This antibody can neutralize poliovirus in the intestine, the site of primary infection. The live attenuated Sabin poliovirus vaccine is effective because it elicits a strong mucosal IgA response and provide intestinal immunity. In contrast, the injected (Salk) polio vaccine does not produce intestinal immunity, and therefore is less effective at preventing spread of poliovirus in a population.

The vast majority of influenza vaccines are administered by injection and stimulate the production of IgG antibodies; they are poor inducers of mucosal IgA antibodies. The efficacy of influenza vaccines would likely be markedly improved if they could be designed to stimulate mucosal immunity. Flumist is a licensed, intranasally-administered infectious virus vaccine that has been shown to stimulate both mucosal and systemic immunity. Nine clinical trials have been conducted in children comparing the efficacy of Flumist with inactivated vaccine or placebo. An analysis of the results suggests that the intranasally administered vaccine is more effective in preventing influenza. These results underscore the role of local immunity in resistance to respiratory pathogens.

Rhorer, J., Ambrose, C., Dickinson, S., Hamilton, H., Oleka, N., Malinoski, F., & Wittes, J. (2009). Efficacy of live attenuated influenza vaccine in children: A meta-analysis of nine randomized clinical trials Vaccine, 27 (7), 1101-1110 DOI: 10.1016/j.vaccine.2008.11.093

http://www.virology.ws/2009/07/24/virus-neutralization-by-antibodies/