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.
Highlights
Influenza A and influenza B viruses circulate within the human population and give rise to seasonal epidemics which are kept in check with an annual vaccination program.Influenza A represents a further public health challenge as it can cross the species barrier between animals and humans leading to occasional pandemics with potentially very high mortality and morbidity
This review summarizes the status and applications of single domain antibodies with broad reactivity against influenza virus
The limitations of conventional monoclonal antibodies have driven considerable interest in single domain antibodies owing to their small size, flexible formatting and high stability
Summary
Influenza A and influenza B viruses circulate within the human population and give rise to seasonal epidemics which are kept in check with an annual vaccination program. There are individuals who have immunity to strains to which they have not previously been exposed, which suggested that cross protective immunity is possible and that epitopes that can elicit such a response exist [11,12] This was confirmed in 1993 with the isolation of a monoclonal antibody, C179, that could neutralize viruses belonging to several different subtypes [13]. It has been observed that human monoclonal antibodies to influenza HA show biases for certain germline segments and can form functional broadly neutralizing antibodies with these segments after very limited somatic hypermutation in vivo This sequence convergence suggests that such antibodies are the result of an early or immediate response to infection potentially guided by previous exposure to influenza [53,54,55]. We discuss how targeting conserved epitopes, reformatting to multi-domain molecules or generating oligoclonal cocktails of sdAbs may provide complementary routes to mitigate the virus’s ability to change and escape detection for applications in vaccine potency testing and as a new class of immunotherapeutics
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