Generation of potent neutralizing human monoclonal antibodies against cytomegalovirus infection from immune B cells

Funaro, Ada; Gribaudo, Giorgio; Luganini, Anna; Ortolan, Erika; Lo Buono, Nicola; Vicenzi, Elisa; Cassetta, Luca; Landolfo, Santo; Buick, Richard; Falciola, Luca; Murphy, Marianne; Garotta, Gianni; Malavasi, Fabio

The validity of the SEQUENTIAL method was evaluated by using it in a project to produce neutralizing human mAbs against HCMV, a leading cause of morbidity and mortality in immunocompromised individuals and the most serious pathogenetic agent in transplant patients [15, 36, 37] . In the absence of other therapies such as vaccines [38] , these patients are treated with antivirals, which are often associated with considerable side effects and the emergence of drug-resistant strains. HCMV is also the leading viral cause of congenital infection associated to significant birth defects and neurological damage for which no effective therapies are available before birth [13, 39] . Hyperimmune globulins specific for HCMV are beneficial in both conditions for the prevention and treatment of these infections [40, 41] . Further, transfer of memory B cells from immune animals to severely immunodeficient recipients confers long-term protection from lethal murine CMV infection. This indicates that the humoral immune response is effective against CMV infection in the absence of a T cell-mediated response [42] . Natural human mAbs with stronger neutralizing activity than that of currently available immunoglobulin preparations may be a decisive alternative in the prevention of primary and re-activated HCMV infections in immunosuppressed patients, or during high-risk pregnancies [43] .