Prophylactic and therapeutic activity of fully human monoclonal antibodies directed against influenza A M2 protein.
Influenza virus infection is a prevalent disease in humans. Antibodies against hemagglutinin have been shown to prevent infection and hence hemagglutinin is the major constituent of current vaccines. Antibodies directed against the highly conserved extracellular domain of M2 have also been shown to mediate protection against Influenza A infection in various animal models. Active vaccination is generally considered the best approach to combat viral diseases. However, passive immunization is an attractive alternative, particularly in acutely exposed or immune compromized individuals, young children and the elderly. We recently described a novel method for the rapid isolation of natural human antibodies by mammalian cell display. Here we used this approach to isolate human monoclonal antibodies directed against the highly conserved extracellular domain of the Influenza A M2 protein. The identified antibodies bound M2 peptide with high affinities, recognized native cell-surface expressed M2 and protected mice from a lethal influenza virus challenge. Moreover, therapeutic treatment up to 2 days after infection was effective, suggesting that M2-specific monoclonals have a great potential as immunotherapeutic agents against Influenza infection.
Beerli
Roger R
RR
Cytos Biotechnology AG, Wagistrasse 25, CH-8952 Schlieren, Switzerland. roger.beerli@cytos.com
Bauer
Monika
M
Schmitz
Nicole
N
Buser
Regula B
RB
Gwerder
Myriam
M
Muntwiler
Simone
S
Renner
Wolfgang A
WA
Saudan
Philippe
P
Bachmann
Martin F
MF
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D000918:Antibody Specificity; D002460:Cell Line; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D016896:Treatment Outcome; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000086082:Viroporin Proteins
D000911:Antibodies, Monoclonal; D007252:Influenza Vaccines; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins