Involvement of the complement system in the protection of mice from challenge with respiratory syncytial virus Long strain following passive immunization with monoclonal antibody 18A2B2.
Passive immunization of mice with 131 micrograms of the non-neutralizing monoclonal antibody (mAb) 18A2B2, directed against the A subgroup epitope of the G glycoprotein of respiratory syncytial virus Long strain (RSV), confers protection against viral i.n. challenge. The role of the Fc fragment of this antibody as well as the involvement of antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytolysis towards protection was evaluated in vivo. Passive immunization with the Fab fragment alone (618-907 micrograms mouse-1) was unable to confer protection in mice. Furthermore, we passively immunized with the mAb 18A2B2 SCID beige mice, which are deficient in natural killer (NK) cell activity, to ascertain the role of NK cells in the protective mechanism. These mice were free of virus 5 days following viral challenge, indicating that NK cells do not contribute significantly towards the protective action of this antibody. Moreover, passively immunized BALB/c mice decomplemented with 8-10 U of cobra venom factor (CoVF) and DBA/2J mice (C5 deficient) were only partially protected. These findings suggest that in mice the alternative and classical pathways of the complement system are involved in the passive protection mechanism conferred by the non-neutralizing mAb 18A2B2. To our knowledge, it is the first description of a protective mechanism in mice that involves a non-neutralizing antibody and the complement system.
Corbeil
S
S
Centre de Recherche en Virologie, Institut Armand-Frappier, Université du Québec, Laval, Canada.
Seguin
C
C
Trudel
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003165:Complement System Proteins / Q000276:immunology / Q000502:physiology*; D005260:Female; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D015678:Viral Structural Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D015678:Viral Structural Proteins; D003165:Complement System Proteins