The Neonatal Fc Receptor and Complement Fixation Facilitate Prophylactic Vaccine-Mediated Humoral Protection against Viral Infection in the Ocular Mucosa.
J Immunol
; 199(5): 1898-1911, 2017 09 01.
Article
en En
| MEDLINE
| ID: mdl-28760885
ABSTRACT
The capacity of licensed vaccines to protect the ocular surface against infection is limited. Common ocular pathogens, such as HSV-1, are increasingly recognized as major contributors to visual morbidity worldwide. Humoral immunity is an essential correlate of protection against HSV-1 pathogenesis and ocular pathology, yet the ability of Ab to protect against HSV-1 is deemed limited due to the slow IgG diffusion rate in the healthy cornea. We show that a live-attenuated HSV-1 vaccine elicits humoral immune responses that are unparalleled by a glycoprotein subunit vaccine vis-à-vis Ab persistence and host protection. The live-attenuated vaccine was used to assess the impact of the immunization route on vaccine efficacy. The hierarchical rankings of primary immunization route with respect to efficacy were s.c. ≥ mucosal > i.m. Prime-boost vaccination via sequential s.c. and i.m. administration yielded greater efficacy than any other primary immunization route alone. Moreover, our data support a role for complement in prophylactic protection, as evidenced by intracellular deposition of C3d in the corneal epithelium of vaccinated animals following challenge and delayed viral clearance in C3-deficient mice. We also identify that the neonatal Fc receptor (FcRn) is upregulated in the cornea following infection or injury concomitant with increased Ab perfusion. Lastly, selective small interfering RNA-mediated knockdown of FcRn in the cornea impeded protection against ocular HSV-1 challenge in vaccinated mice. Collectively, these findings establish a novel mechanism of humoral protection in the eye involving FcRn and may facilitate vaccine and therapeutic development for other ocular surface diseases.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Vacunas Virales
/
Receptores Fc
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Antígenos de Histocompatibilidad Clase I
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Herpesvirus Humano 1
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Córnea
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Herpes Simple
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Membrana Mucosa
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2017
Tipo del documento:
Article