A potential role for monoclonal antibodies in prophylactic and therapeutic treatment of influenza Nicasio Mancini ⇑,1 , Laura Solforosi 1 , Nicola Clementi, Donata De Marco, Massimo Clementi, Roberto Burioni Laboratorio di Microbiologia e Virologia, Università ‘‘Vita-Salute’’ San Raffaele, Milano, Italy article info Article history: Received 21 March 2011 Revised 19 May 2011 Accepted 12 July 2011 Available online 21 July 2011 Keywords: Monoclonal antibodies Influenza viruses Universal epitopes abstract The role of humoral response in the effective control of infection by influenza viruses is well known, but the protection is usually limited to the infecting or vaccinating isolate and to few related strains. Recent studies have evidenced the existence of B-cell epitopes broadly conserved among different influenza sub- types recognized by monoclonal antibodies endowed with unprecedented broad activity. In this review, all major monoclonal antibodies directed against different influenza virus proteins are reported and their potential in the design of new anti-influenza prophylactic or therapeutic strategies is discussed. Ó 2011 Elsevier B.V. All rights reserved. 1. Introduction Influenza is the most recurring respiratory affection in humans, and its socio-economical impact has been often dramatic. During the 20th century, influenza A viruses have afflicted the human race with three pandemics: in 1918 caused by a virus belonging to the H1N1 subtype, in 1957 caused by a H2N2 isolate, and in 1968 caused by a H3N2 isolate (Palese, 2004). In 2009 a H1N1 reassor- tant strain has caused the first pandemic of the new century (Gir- ard et al., 2010) and is now the cause, together with H3N2, of the ongoing seasonal epidemic. The 2009 pandemic proved to be not as severe as initially feared, but it drew attention to the continuous risk of a major influenza pandemic caused by a completely novel strain seriously threatening global public health. This inevitable risk, due to episodic major antigenic changes on the surface of influenza virions (antigenic shift) will always face humankind and the potentially dramatic impact of the next major pandemic is not predictable. Apart from containment and preventive public health strategies which will not be discussed in this review, the only prophylactic or therapeutic measures now available for governments and public health agencies around the world are two classes of anti-influenza drugs (neuraminidase inhibitors and M2 blockers) and the annual vaccination campaigns. Several concerns have been raised regarding the real cost-effectiveness of the broad prophylactic use of available drugs (Burch et al., 2009a,b), which have been and are currently stockpiled by public health agencies in anticipation of a possible fu- ture pandemic. The concerns include the need of their prompt administration to be effective (Beigel and Bray, 2008), the rapid emergence of resistant isolates (Cheng et al., 2009; Ramirez-Gonz- alez et al., 2011) and several associated side-effects especially in high-risk categories, such as children and pregnant women (Burioni et al., 2009a,b; Kitching et al., 2009). In addition, current influenza vaccination campaigns are based on a presumptive process: each year, a new vaccine is prepared that aims to match the strains pre- dicted to circulate in the coming flu season. This is because the virus continuously undergoes genetic mutation to escape from the host immune response and the resulting hypervariability is particularly evident on the two major influenza surface proteins, hemagglutinin (HA) and neuraminidase (NA) (Gamblin and Skehel, 2010). This con- tinuous variability (antigenic drift) is the molecular basis causing seasonal influenza infections (Carrat and Flahault, 2007; Webster et al., 1992), and it is the molecular factor determining the already observed mismatches between the predicted vaccinal strains and the circulating strain, therefore causing vaccine ineffectiveness (Monto et al., 2009). Moreover, vaccine ineffectiveness is highly probable in the case of the major antigenic variations associated with a future novel pandemic strain. In order to overcome the drawbacks of the available prophylac- tic and therapeutic approaches, new broad-range strategies are therefore needed and, accordingly, several research strategies have been already described (Ansaldi et al., 2009; Monto et al., 2009; Nabel and Fauci, 2010; Stanekova and Vareckova, 2010; Steel et al., 2010). A pivotal role in this field will certainly be played 0166-3542/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.antiviral.2011.07.013 ⇑ Corresponding author. Address: Laboratorio di Microbiologia e Virologia, Università ‘‘Vita-Salute’’ San Raffaele, DIBIT2, 2° piano, via Olgettina 58, 20132 Milano, Italy. Tel.: +39 02 2643 4195; fax: +39 02 2643 2640. E-mail address: mancini.nicasio@hsr.it (N. Mancini). 1 These authors contributed equally to the paper. Antiviral Research 92 (2011) 15–26 Contents lists available at ScienceDirect Antiviral Research journal homepage: www.elsevier.com/locate/antiviral