Single-Domain Antibodies and Their Formatting to Combat Viral Infections

Abstract

Since their discovery in the 1990s, single-domain antibodies (VHHs), also known as Nanobodies®, have changed the landscape of affinity reagents. The outstanding solubility, stability, and specificity of VHHs, as well as their small size, ease of production and formatting flexibility favor VHHs over conventional antibody formats for many applications. The exceptional ease by which it is possible to fuse VHHs with different molecular modules has been particularly explored in the context of viral infections. In this review, we focus on VHH formats that have been developed to combat viruses including influenza viruses, human immunodeficiency virus-1 (HIV-1), and human respiratory syncytial virus (RSV). Such formats may significantly increase the affinity, half-life, breadth of protection of an antiviral VHH and reduce the risk of viral escape. In addition, VHHs can be equipped with effector functions, for example to guide components of the immune system with high precision to sites of viral infection.

Structural Basis for Potent Neutralization of Betacoronaviruses by Single-domain Camelid Antibodies

“…and are known to have enhanced thermal stability and chemostability compared to most 56 antibodies (De Vlieger et al, 2018;Dumoulin et al, 2002;Govaert et al, 2012;Laursen et al, 57 2018;van der Linden et al, 1999). Their advantageous biophysical properties have led to the 58 evaluation of several VHHs as therapeutics against common respiratory pathogens, such as 59 respiratory syncytial virus (RSV) (Detalle et al, 2016;Rossey et al, 2017).…”

Selective Engagement of FcγRIV by a M2e-Specific Single Domain Antibody Construct Protects Against Influenza A Virus Infection

“…Due to their outstanding stability and solubility, as well as their small size (∼15 kDa), ease of production and formatting flexibility, they are highly versatile building blocks for the development of new antivirals. Next to a direct antiviral effect, VHHs can also easily be formatted (e.g., by generating Fc fusions) to recruit host effector functions (23). These features, combined with the possibility to deliver therapeutic VHHs into the lung environment, and maintained stability after prolonged storage, make VHH-based anti-influenza biologicals especially attractive for epidemic as well as pandemic preparedness plans (24)(25)(26)(27).…”

Development of humanized tri-specific nanobodies with potent neutralization for SARS-CoV-2

“…Especially during pandemics such as COVID-19 when rapid production of antibodies in high quantities is essential, the developability and manufacturability of the antibodies play even crucial roles. Our design has the advantage of using llama VHH nanobodies that have high stability 17,18 . Indeed, the biochemical and biophysical characteristics of the multi-speci c VHH-Fc show that they can be puri ed in high quantity, have better aggregation resistance, and have favorable thermostability.…”