- The deployment of antibodies as antiviral agents has progressed through a number of stages over the years, corresponding to increasing levels of potency of the reagent administered.
- Passive immunotherapy began with immune serum over a century ago, then progressed to polyclonal antibodies, then mAbs and now into highly potent human mAbs called as super-antibodies.
- Super-antibodies are monoclonal antibodies against targeted virus.
Many acute viral infections induce robust neutralizing antibody responses in the large majority of individuals.
There are “EVASION LITE” and “EVASION STRONG” viruses.
Evasion lite viruses display limited antigenic variability in their surface protein (or proteins) or show considerable variability but nevertheless express immunodominant, conserved epitopes. For these types of viruses, the isolation of super-antibodies from immune donors has been achieved in a fairly straightforward manner.
e.g. measles virus, poliovirus, chikungunya virus and RSV8–11
Evasion strong viruses have evolved mechanisms to evade effective neutralizing antibody responses and induce such responses at much lower levels. Effective responses in the context of infection with highly antigenically variable viruses refers not only to their neutralization potency but also to their effectiveness against diverse circulating global isolates, often referred to as breadth.
In these type of viruses only a proportion of infected individuals, sometimes quite small, will generate broad and potent neutralizing antibody responses. Furthermore, within these individuals, potent broadly neutralizing antibody (bnAb) specificities generally constitute only a small fraction of the antigen-specific memory B cell pool.
e.g. HIV, influenza virus, Ebola virus and Lassa virus
Human antiviral neutralizing mAbs have been isolated using various different technologies, including
i. Combinatorial display libraries
ii. Human immunoglobulin transgenic mice
iii. Single B cell isolation methods
iv. B cell immortalization
v. B cell culture
- Only a single antiviral mAb, the RSV-specific antibody palivizumab, is in widespread clinical use. But there are several Super-antibodies are in phase-III of development.