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Trop. Med. Infect. Dis. 2017, 2(3), 22; doi:10.3390/tropicalmed2030022

Protection Against CNS-Targeted Rabies Virus Infection is Dependent upon Type-1 Immune Mechanisms Induced by Live-Attenuated Rabies Vaccines

1
Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA 19017, USA
2
Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA 19017, USA
*
Author to whom correspondence should be addressed.
Received: 17 May 2017 / Revised: 28 June 2017 / Accepted: 29 June 2017 / Published: 4 July 2017
(This article belongs to the Special Issue Rabies Symptoms, Diagnosis, Prophylaxis and Treatment)
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Abstract

Rabies remains a major public health issue worldwide, especially in developing countries where access to medical care can represent a real challenge. While there is still no cure for rabies, it is a vaccine-preventable disease with pre- and post-exposure prophylaxis regimens approved by the World Health Organization (WHO). However, many rabies-exposed individuals have limited access to vaccines and virus-neutralizing antibodies approved for post-exposure prophylaxis. Unfortunately, any delay in the administration of these reagents can have lethal consequences. This highlights the need to develop cost-effective immunological reagents with a greater window of efficacy. Live-attenuated vaccine strains of rabies virus presents a potential treatment in filling this gap. We show here that immunization with live-attenuated vaccines provide long-lasting rabies immunity, superior to the protection induced by inactivated vaccines. In the absence of an immunostimulatory adjuvant, vaccination with multiple doses of inactivated rabies virus induces a type-2 immune response. This type of immunity is highly effective at inducing neutralizing antibody but has limited efficacy in clearing the virus from central nervous system (CNS) tissues. In contrast, a single infection with live-attenuated rabies vaccine safely drives a type-1 immune response, associated with both the production of a neutralizing antibody and the clearance of wild-type rabies virus from CNS tissues. These results indicate that live-attenuated rabies strains have the potential to be more effective in post-exposure prophylaxis than conventional inactivated vaccines. View Full-Text
Keywords: rabies; vaccine; type-1 immunity; type-2 immunity rabies; vaccine; type-1 immunity; type-2 immunity
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Lebrun, A.; Garcia, S.; Li, J.; Kean, R.B.; Hooper, D.C. Protection Against CNS-Targeted Rabies Virus Infection is Dependent upon Type-1 Immune Mechanisms Induced by Live-Attenuated Rabies Vaccines. Trop. Med. Infect. Dis. 2017, 2, 22.

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