Limited contribution of humoral immunity to the clearance of measles viremia in rhesus monkeys.
The development of an improved vaccine for controlling measles virus (MV) infections in the developing world will require an understanding of the immune mechanisms responsible for the clearance of this virus. To evaluate the role of humoral immunity in the containment of MV, rhesus monkeys were treated at the time of MV challenge with either anti-CD20 monoclonal antibody (MAb) infusion, to deplete B lymphocytes, or both anti-CD20 and anti-CD8 MAb, to deplete both B lymphocytes and CD8+ effector T lymphocytes. Although the MV-specific antibody response in CD20+ lymphocyte-depleted monkeys was delayed by >1 week, the kinetics of MV clearance did not differ from those for monkeys that received control MAb. Furthermore, unusual clinical sequelae of MV infection were not observed in these monkeys. In contrast, MV-infected rhesus monkeys depleted of both CD20+ and CD8+ lymphocytes had a prolonged duration of viremia and developed a desquamating skin rash. These findings indicate that humoral immunity plays a limited role in the control of MV replication in an MV-naive individual and suggest that new measles vaccination strategies should focus on the elicitation of cell-mediated immune responses, in addition to neutralizing antibodies, to facilitate rapid elimination of locally replicating virus.
Permar
Sallie R
SR
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Klumpp
Sherry A
SA
Mansfield
Keith G
KG
Carville
Angela A L
AA
Gorgone
Darci A
DA
Lifton
Michelle A
MA
Schmitz
Jörn E
JE
Reimann
Keith A
KA
Polack
Fernando P
FP
Griffin
Diane E
DE
Letvin
Norman L
NL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000097:blood / Q000276:immunology*; D000917:Antibody Formation; D018951:Antigens, CD20 / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D008457:Measles / Q000276:immunology / Q000821:virology*; D008459:Measles virus / Q000276:immunology / Q000472:pathogenicity*; D014766:Viremia / Q000276:immunology / Q000821:virology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D018951:Antigens, CD20