Coronavirus-induced encephalomyelitis: balance between protection and immune pathology depends on the immunization schedule with spike protein S

Abstract

The neurotropic mouse hepatitis virus MHV-JHM induces central nervous system (CNS) demyelination in Lewis rats that pathologically resembles CNS lesions in multiple sclerosis. The mechanisms of MHV-JHMinduced demyelination remain unclear and several studies have implicated the role of the immune response in this process. We have shown previously that protective immunity against MHV-JHM-induced encephalomyelitis was induced by immunization with a vaccinia virus (VV) recombinant expressing MHV-JHM Sprotein (VV-S). Here, we present evidence that the time of MHV-JHM challenge after immunization with VV-S plays a critical role in protective immunity. The induction of virus-neutralizing S-protein-specific antibodies prior to the MHV-JHM challenge modulates the disease process and a subacute encephalomyelitis based on a persistent virus infection developed. Typical pathological alterations were lesions of inflammatory demyelination. In addition, the results indicate that after seroconversion, CD8 ÷ T cells were no longer essential for virus elimination in contrast to their role in protection during acute encephalomyelitis.

Antibody and cytokine responses in kittens during the development of feline infectious peritonitis (FIP)

“…It is generally the spike (S) protein that stimulates the production of both neutralising and enhancing antibodies (Spaan et al, 1988 and references therein;Vennema et al, 1990;Hohdatsu et al, 1991;Olsen et al, 1992Olsen et al, , 1993Corapi et al, 1992Corapi et al, , 1995, and although the exact relationship between enhancing and neutralising epitopes remains to be determined, a number of attempts have been made to develop suitable subunit vaccines. While some success has been seen with the murine MHV system (Flory et al, 1993(Flory et al, , 1995Brown et al, 1994), in cats recombinant vaccinia vectors expressing FCoV, CCV or TGEV S proteins have generally caused enhancement of disease rather than protection (Vennema et al, 1990;Chalmers et al, 1993). More recent work has tried to define the exact locations of both the neutralising and enhancing epitopes (Hohdatsu et al, 1991;Corapi et al, 1992Corapi et al, , 1995Olsen et al, 1992Olsen et al, , 1993.…”

Generation and Characterization of DNA Vaccines Targeting the Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus

“…For these reasons, we generated vaccinia virus expressing SARS-CoV N protein for use as a surrogate viral challenge model. The development of such a model for testing of our vaccine strategy is not without precedent, as vaccinia virus has been previously used in several prior studies as a substitute viral challenge model (1,14). While these studies may show a good correlation between the reduction of vaccinia virus titer and vaccine potency, it would be preferable for our research to explore vaccine efficacy against live SARS-CoV in a near-human model.…”

Immunopathological aspects of coronavirus infections

“…On the other hand, if the immune response fails to eliminate the virus, a persistent infection may be established. Depending on the experimental conditions, an immune-mediated demyelination can be induced [6,22,24,82,92,97].…”

“…As shown by depletion experiments, the protective effect depends on the presence of S protein-specific CD8 § T cells. However, a subclinical and protracted course of disease associated with a persistent infection was induced if the MHV-JHM challenge was performed 3 weeks after vaccination [24]. Employing this immunisation schedule, the CD8 § T cells appear to be of less importance.…”