Efficacy of topical immunoglobulins against experimental adenoviral ocular infection.
OBJECTIVE
Presently, there is no U.S. Federal Drug Administration (FDA)-approved antiviral therapy for the treatment of adenoviral (Ad) ocular infections. The goal of the present study was to determine the antiviral efficacy of human immunoglobulin (Ig), a preparation of highly purified and concentrated immunoglobulin (IgG) antibodies isolated from a large pool of human plasma donors, in vitro and on acute Ad replication in the Ad5 New Zealand White (NZW) rabbit ocular model.


METHODS
The antiviral activity of human Ig against multiple wild-type and human ocular isolates of adenovirus serotypes was investigated in vitro by using neutralizing assays in different human epithelial cell lines. In vivo bilateral topical ocular toxicity and antiviral efficacy were evaluated with established Ad5/NZW rabbit ocular models. In vivo Ig antiviral results were compared with those obtained with topical 0.5% cidofovir and saline.


RESULTS
In three different epithelial cell lines, <or=6.25 mg/mL of the Ig neutralized several wild-type adenoviral serotypes that cause ocular infections. A dose of <or=10 mg/mL neutralized 88% of ocular isolates of the adenovirus serotypes. After treatment of infected animals, adenovirus-positive cultures per total cultures (days 1-14; P = 0.021), the duration of Ad5 shedding, (P = 0.008), and the mean combined ocular viral titer during the early (days 1-5; P = 0.0001) and the late (days 7-14; P = 0.013) phases of infection were significantly lower in Ig-treated animals than in saline-treated animals and were similar to those in cidofovir-treated animals.


CONCLUSIONS
Ig demonstrated antiviral properties against multiple adenoviral serotypes in vitro and in the Ad5/NZW rabbit ocular model. Further studies are needed to advance topical immunoglobulin for treatment and prophylaxis of ocular infections.
Nwanegbo
Edward C
EC
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.
Romanowski
Eric G
EG
Gordon
Y Jerold
YJ
Gambotto
Andrea
A
D000258:Adenovirus Infections, Human / Q000188:drug therapy* / Q000821:virology; D000260:Adenoviruses, Human / Q000302:isolation & purification* / Q000502:physiology; D000287:Administration, Topical; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000633:toxicity; D018929:Cell Culture Techniques; D000077404:Cidofovir; D003228:Conjunctiva / Q000821:virology; D003315:Cornea / Q000821:virology; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000821:virology; D015828:Eye Infections, Viral / Q000188:drug therapy* / Q000821:virology; D005434:Flow Cytometry; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use* / Q000633:toxicity; D007155:Immunologic Factors / Q000627:therapeutic use* / Q000633:toxicity; D007637:Keratoconjunctivitis / Q000188:drug therapy* / Q000821:virology; D063065:Organophosphonates / Q000008:administration & dosage / Q000633:toxicity; D011817:Rabbits; D016896:Treatment Outcome; D014776:Virus Cultivation; D014779:Virus Replication / Q000187:drug effects; D017201:Virus Shedding
D000998:Antiviral Agents; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir