Broad Reactivity Single Domain Antibodies against Influenza Virus and Their Applications to Vaccine Potency Testing and Immunotherapy

Abstract

The antigenic variability of influenza presents many challenges to the development of vaccines and immunotherapeutics. However, it is apparent that there are epitopes on the virus that have evolved to remain largely constant due to their functional importance. These more conserved regions are often hidden and difficult to access by the human immune system but recent efforts have shown that these may be the Achilles heel of the virus through development and delivery of appropriate biological drugs. Amongst these, single domain antibodies (sdAbs) are equipped to target these vulnerabilities of the influenza virus due to their preference for concave epitopes on protein surfaces, their small size, flexible reformatting and high stability. Single domain antibodies are well placed to provide a new generation of robust analytical reagents and therapeutics to support the constant efforts to keep influenza in check.

Central Nervous System Delivery of Antibodies and Their Single-Domain Antibodies and Variable Fragment Derivatives with Focus on Intranasal Nose to Brain Administration

“…SdAbs have been developed to fight infectious diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza [ 134 ]. ‘AeroNabs’, aerosol-formulated nanobodies, could be used with a nasal spray or inhaler for personal protection against coronavirus disease 2019 (COVID-19) [ 135 ].…”

A Low-Dose Triple Antibody Cocktail Against the Ectodomain of the Matrix Protein 2 of Influenza A Is A Universally Effective and Viral Escape Mutant Resistant Therapeutic Agent

“…M2 is essential for viral core disassembly, assembly, and budding [19]. However, most M2especific antibodies do not neutralize IAVs [20,26,33,[37][38][39][40], and those who do neutralize certain IAV strains do so at the cost of universality [23,32,[40][41][42][43]. It is important to note that neutralization, while effective, is not a requirement for protection from lethal IAV challenge, as demonstrated by non-neutralizing but protective antibodies to M2e-mAbs and influenza's HA stalk region [33,44,45].…”

Therapeutic applications of nanobodies against SARS-CoV-2 and other viral infections: Current update

“…Yep et al have elucidated that these membrane proteins can be targeted to prepare several neutralizing mAbs. A closer look at the structural conformation of these proteins proves the presence of several concave surfaces makes it extremely suitable for preparing nanobodies [41] . The R1a-B6 is one of the nanobody that exhibits a cross-neutralizing action providing a broader aspect to cure the viral infection.…”