Antigenic drift, the gradual accumulation of amino acid substitutions in the influenza virus hemagglutinin (HA) receptor protein, enables viral immune evasion. Antibodies (Abs) specific for the drift-resistant HA stem region are a promising universal influenza vaccine target. Although anti-stem Abs are not believed to block viral attachment, here we show that complement component 1q (C1q), a 460-kilodalton protein with six Ab Fc-binding domains, confers attachment inhibition to anti-stem Abs and enhances their fusion and neuraminidase inhibition. As a result, virus neutralization activity in vitro is boosted up to 30-fold, and in vivo protection from influenza PR8 infection in mice is enhanced. These effects reflect increased steric hindrance and not increased Ab avidity. C1q greatly expands the anti-stem Ab viral escape repertoire to include residues throughout the HA, some of which cause antigenic alterations in the globular region or modulate HA receptor avidity. We also show that C1q enhances the neutralization activity of non–receptor binding domain anti–SARS-CoV-2 spike Abs, an effect dependent on spike density on the virion surface. These findings demonstrate that C1q can greatly expand Ab function and thereby contribute to viral evolution and immune escape.

中文翻译：

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C1q 使流感血凝素干结合抗体能够阻止病毒附着并扩大抗体逃逸库

抗原漂移，即流感病毒血凝素（HA）受体蛋白中氨基酸取代的逐渐积累，使得病毒能够逃避免疫。抗漂移 HA 干区特异性抗体 (Abs) 是有前景的通用流感疫苗靶点。虽然抗干抗体不被认为可以阻止病毒附着，但在这里我们表明，补体成分 1q (C1q)（一种具有 6 个 Ab Fc 结合域的 460 千道尔顿蛋白质）赋予抗干抗体附着抑制作用，并增强它们的融合和融合。神经氨酸酶抑制。结果，体外病毒中和活​​性提高了30倍，体内对小鼠流感PR8感染的保护也增强了。这些效应反映了空间位阻的增加，而不是抗体亲和力的增加。 C1q 极大地扩展了抗干抗体病毒逃逸库，包括整个 HA 中的残基，其中一些残基会导致球状区域的抗原改变或调节 HA 受体亲合力。我们还表明，C1q 增强非受体结合域抗 SARS-CoV-2 刺突抗体的中和活性，这种作用取决于病毒颗粒表面的刺突密度。这些发现表明，C1q 可以极大地扩展 Ab 功能，从而有助于病毒进化和免疫逃逸。