Combination therapy of vaccinia virus infection with human anti-H3 and anti-B5 monoclonal antibodies in a small animal model.
BACKGROUND
Treatment of rare severe side effects of vaccinia virus (VACV) immunization in humans is currently very challenging. VACV possesses two immunologically distinct virion forms in vivo - intracellular mature virion (MV, IMV) and extracellular virion (EV, EEV).


METHODS
Antibody-mediated therapeutic efficacy was determined against VACV infection in a small animal model of progressive vaccinia. The model consisted of severe combined immunodeficiency mice infected with VACV New York City Board of Health vaccine strain and treated with monoclonal antibodies (mAbs).


RESULTS
Here, we show that combination therapy with two fully human mAbs against an immunodominant MV antigen, H3 (H3L), and an EV antigen, B5 (B5R), provides significantly better protection against disease and death than either single human monoclonal or human vaccinia immune globulin, the currently licensed therapeutic for side effects of smallpox vaccination.


CONCLUSIONS
The preclinical studies validate that this combination of mAbs against H3 and B5 is a promising approach as a poxvirus infection treatment for use in humans.
McCausland
Megan M
MM
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
Benhnia
Mohammed Rafii-El-Idrissi
MR
Crickard
Lindsay
L
Laudenslager
John
J
Granger
Steven W
SW
Tahara
Tomoyuki
T
Kubo
Ralph
R
Koriazova
Lilia
L
Kato
Shinichiro
S
Crotty
Shane
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000627:therapeutic use; D002352:Carrier Proteins / Q000276:immunology*; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009500:Neutralization Tests; D016896:Treatment Outcome; D014615:Vaccinia / Q000188:drug therapy* / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; C534336:B5 protein, vaccinia virus; D002352:Carrier Proteins; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; C406065:envelope H3L protein, Vaccinia virus