I am currently researching an article about rabies for possible publication in a medical laboratory journal. I understand that, as the rabies virus travels along the nervous system from the site of inoculation as it makes its way to the brain, it largely avoids the body's immune system. Nevertheless, it is clear that prophylactic rabies vaccine as well as post-exposure vaccine and immune globulin can successfully protect an individual against developing rabies. If the rabies virus is in effect shielded from the immune system because it's within the CNS, what is the actual process by which rabies vaccines help the immune system attack the virus? Is there a particular class of cells responsible for neutralizing the virus? At what point do circulating immune cells have contact with the CNS and thus the virus? Thank you. John
Hello John Buhler
Rabies virus (RABV) is a strictly neurotropic virus that slowly propagates in the nervous system (NS) of the infected host from the site of entry (usually due to a bite) up to the site of exit (salivary glands). Successful achievement of the virus cycle relies on the preservation of the neuronal network. Once RABV has entered the NS, its progression is not interrupted either by destruction of the infected neurons or by the immune response, which are major host mechanisms for combating viral infection.
RABV has developed two main mechanisms to escape the host defenses:
1. Type I interferon is the main mediator of antiviral innate immune responses, but RABVs seem to be poor inducers of type I interferon, and such dampened type I interferon initial responses at the virus peripheral entry sites might only partially eliminate replication.
2. Several mechanisms could enable RABV to escape or manipulate adaptive immune surveillance in the nervous system. Upregulation of FASLG expression and subsequent activation of Fas ligand could induce apoptosis of antigen-activated T cells and contribute to the termination of the immune response. The expression of HLA class I histocompatibility antigen, α chain G (HLAG), a nonclassical, immunosuppressive HLA, and upregulation of the expression of programmed cell death ligand 1 (PDL1; also known as B7H1) could inhibit T cell proliferation and apoptosis.
One reason for a failure to protect in humans may be the poor immunological response the virus provokes, despite the period between exposure to virus and the development of disease being measured in months. Few individuals have measurable neutralizing antibody on presentation with disease, although in many cases this develops as symptoms become more severe. Furthermore, when antibody is detected in serum it rarely appears in cerebrospinal fluid suggesting limited penetration into the CNS, the site where it is most needed. The virus-neutralizing antibodies (VNAs), which might be detected in the acute neurological phase of naturally acquired RABV infection in humans, are considered to be unable to prevent a fatal outcome of the infection.
The principal immunological correlate of protection produced by vaccination is the neutralizing antibody. The goal of vaccination is to induce VNAs against glycoprotein that provide protection against RABV infection. The vaccine does not act on the virus but instead it acts on the patient.
Therefore, the vaccine is given prior to rabies exposure. It promotes immunity by triggering an immune response. The production of antibodies takes around 7-10 days. If given after a bite, the rabies immune globulin or anti-rabies serum is given in conjunction with the rabies vaccine to provide immune protection until an antibody response can occur.
Best.