Noailly Blandine, Yaugel-Novoa Melyssa, Werquin Justine, Jospin Fabienne, Drocourt Daniel, Bourlet Thomas, Rochereau Nicolas, Paul Stéphane
CIRI-Centre International de Recherche en Infectiologie, Team GIMAP, Université Claude Bernard Lyon 1, Inserm, U1111, CNRS, UMR530, CIC 1408 Vaccinology, 42023 Saint-Etienne, France.
Cayla InvivoGen, 31400 Toulouse, France.
Vaccines (Basel). 2022 Jun 6;10(6):903. doi: 10.3390/vaccines10060903.
Broadly neutralizing antibodies (bNAbs) offer promising opportunities for preventing HIV-1 infection. The protection mechanisms of bNAbs involve the Fc domain, as well as their Fab counterpart. Here, different bNAb isotypes including IgG1, IgA1, IgA2, and IgA122 (IgA2 with the hinge of IgA1) were generated and then produced in CHO cells. Their ability to neutralize pseudovirus and primary HIV-1 isolates were measured, as well as their potential ADCC-like activity using a newly developed assay. In our work, gp41-specific IgA seems to be more efficient than IgG1 in inducing ADCC-like activity, but not in its virus neutralization effect. We show that either gp120-specific IgA or IgG1 isotypes are both efficient in neutralizing different viral strains. In contrast, gp120-specific IgG1 was a better ADCC-like inducer than IgA isotypes. These results provide new insights into the neutralization and ADCC-like activity of different bNAbs that might be taken into consideration when searching for new treatments or antibody-based vaccines.
广谱中和抗体（bNAbs）为预防HIV-1感染提供了有前景的机会。bNAbs的保护机制涉及Fc结构域及其Fab结构域。在此，生成了包括IgG1、IgA1、IgA2和IgA122（具有IgA1铰链的IgA2）在内的不同bNAb亚型，然后在CHO细胞中进行生产。测定了它们中和假病毒和原发性HIV-1分离株的能力，以及使用新开发的检测方法测定它们潜在的类ADCC活性。在我们的研究中，gp41特异性IgA在诱导类ADCC活性方面似乎比IgG1更有效，但在病毒中和作用方面并非如此。我们表明，gp120特异性IgA或IgG1亚型在中和不同病毒株方面均有效。相比之下，gp120特异性IgG１作为类ADCC诱导剂比IgA亚型更好。这些结果为不同bNAbs的中和作用和类ADCC活性提供了新的见解，在寻找新的治疗方法或基于抗体的疫苗时可能需要考虑这些见解。
