Antiviral Monoclonal Antibodies: Can They Be More Than Simple Neutralizing Agents?

Abstract

Monoclonal antibodies (mAbs) are increasingly being considered as agents to fight severe viral diseases. So far, they have essentially been selected and used on the basis of their virus-neutralizing activity and/or cell-killing activity to blunt viral propagation via direct mechanisms. There is, however, accumulating evidence that they can also induce long-lasting protective antiviral immunity by recruiting the endogenous immune system of infected individuals during the period of immunotherapy. Exploiting this property may revolutionize antiviral mAb-based immunotherapies, with benefits for both patients and healthcare systems.

A Cytokine Pattern That Differentiates Preseroconversion From Postseroconversion Phases of Primary HIV Infection

“…Modulation of these cytokines might promote an earlier development of autologous neutralizing antibodies that may contribute to faster and long-lasting control of HIV. 35,36 …”

Detailed Protocols for the Selection of Antiviral Human Antibodies from Combinatorial Immune Phage Display Libraries

“…Typically, we inoculate 250 ml in a 1 L baffled Erlenmeyer flask for libraries of large library size up to 10 9 independent bacteria clones. The inoculated volume depends on library diversity and might vary between 50 ml and > 2 l. For libraries cloned from virus-infected donors, an initial library size of 10 7 and inoculating 100 ml is sufficient (Note 1).…”

“…The vast majority of monoclonal antibodies is approved for the treatment of cancers, multiple sclerosis, or rheumatoid arthritis [7]. However, numerous potent human or humanized antiviral antibodies against H5N1 influenza virus, human immunodeficiency virus (HIV), herpes simplex virus (HSV), human cytomegalovirus (CMV), hepatitis C virus (HCV), Ebola virus, severe acute respiratory syndrome (SARS) virus, and other viral infections are in preclinical development, clinical studies, or even approved for antiviral treatment [2,[7][8][9][10][11][12]. Antibodies mostly neutralize free viruses by targeting the initial stages of virus infection described as the binding of free virions to permissive target cells followed by entry and replication [2].…”

Engineering broadly neutralizing antibodies for HIV prevention and therapy

“…Additionally, passively administered anti-HIV antibodies can demonstrate indirect ‘vaccine-like effects’ whereby stimulation of the endogenous host immune response contributes to antiviral activity lasting well beyond the treatment period itself (reviewed [126]). In macaque studies of SIV and SHIV infection, SIV-/SHIV-IG treatment not only delayed disease onset and increased survival rates, but also accelerated de novo production of autologous anti-SIV antibodies [127, 128] and elevated virus-specific CD4+ and CD8+ T cell responses during both acute and chronic infection phases [129].…”