Immune responses and protection induced by mucosal and systemic immunisation with recombinant measles nucleoprotein in a mouse model of measles virus-induced encephalitis

Abstract

In this study the immunogenicity of recombinant nucleoprotein (Np) administered intranasally or intraperitoneally, and its ability to support a systemic protective anti-virus antibody response was examined, in a mouse model of measles virus (MV)-induced encephalitis. Although both intranasal and intraperitoneal routes of immunisation resulted in priming Np- and MV-specific T-cell responses, the intraperitoneal route was shown to prime for a predominantly IgG2a serum anti-MV antibody response of high avidity, which confered complete protection following intracranial challenge with a neuroadapted strain of MV. On the other hand, intranasal priming resulted in a mixed IgG1, IgG2a serum anti-MV antibody response of low avidity, and only 43% of immunised mice survived following intracranial challenge with the neuroadapted strain of MV. These findings suggest that the route of immunisation in combination with an appropriate adjuvant could influence the induction of a quality antibody response with protective capacity.

Measles virus nucleoprotein induces cell-proliferation arrest and apoptosis through NTAIL–NR and NCORE–FcγRIIB1 interactions, respectively

“…MV infection induces both an efficient specific immune response and transient, but profound, immunosuppression contributing to secondary infections and mortality in humans (Beckford et al, 1985;Griffin, 1995;Miller, 1964). Virus clearance is ensured by specific immunity against MV proteins, particularly MV-N, which confers long-life protection against reinfection (Etchart et al, 2001;Olszewska et al, 2001) and includes N-specific T lymphocytes (Etchart et al, 2001;Ilonen et al, 1990;Jacobson et al, 1989;Olszewska et al, 2001;van Binnendijk et al, 1989). Although MV-N is a cytosolic protein, the most abundant and rapidly produced antibodies during MV infection are N specific (Graves et al, 1984;Norrby & Gollmar, 1972).…”

Measles Virus (MV) Nucleoprotein Binds to a Novel Cell Surface Receptor Distinct from FcγRII via Its C-Terminal Domain: Role in MV-Induced Immunosuppression

“…Moreover, efficient helper CD4 ϩ -T and cytotoxic CD8 ϩ -T-cell responses against N are generated during the course of MV infection (23,24,59). MV-N induces, in the absence of other viral proteins, N-specific T-cell responses, a systemic anti-N antibody response, and protection against MV infection (12,39). Thus, MV infection is associated with an effective Nspecific response that leads, with other events, to viral clearance, recovery from disease in 2 weeks, and to a protective immune response against reinfection.…”

Mucosal Herpes Immunity and Immunopathology to Ocular and Genital Herpes Simplex Virus Infections

“…For example, antigens administered intranasally promote vaginal immunity more effectively than antigens given orally, suggesting that there is compartmentalization or regionalization of the mucosal immune system [34, 92]. Intranasal immunization induces IgA not only within the nose and salivary glands, but also in the small intestine lamina propria [94], the remote urinary tract [95], and the vagina [96]. The vascular and lymphatic structure of OMIS and nasolacrimal duct system provide unique anatomical conduits through which the NALT (nasal-associated lymphoid tissue) and OMIS are thought to be immunologically connected and interdependent.…”