Experimental rabies vaccines for humans

Abstract

Rabies remains a global public health threat that kills more than 55,000 people per year. Rabies disproportionately affects children and, therefore, is ranked the seventh most important infectious disease due to years lost. Prevention of human rabies is accomplished by controlling rabies in domestic and wild animals, including the use of vaccination programs. The usefulness of human rabies vaccines is hampered by high cost, complicated vaccination regimens and lack of compliance, especially in areas of Africa and Asia where human rabies infections are endemic. A single-dose vaccine would greatly benefit efforts to combat this global health threat. However, a single-dose vaccine based on current inactivated vaccines does not appear feasible and other approaches are needed. Technology has advanced since modern human rabies vaccines were developed over 40 years ago. In addition, our understanding of immunological principles that influence the outcome of vaccination has increased. This article describes the current status of inactivated rabies virus vaccines and recent developments arising from the use of reverse genetics technologies designed to develop replication-deficient or single-cycle live rabies virus-based vectors for use as a single-dose rabies vaccine for humans.

Keywords::

• attenuated rabies vaccines
• post-exposure vaccines
• pre-exposure vaccines
• rabies vaccines
• replication-deficient vectors
• reverse genetics
• single-cycle vectors

Acknowledgments

The author thanks Paul Schiffmacher for preparation of the figures and Eric Brown for careful review of the manuscript.

Financial & competing interests disclosure

James P McGettigan discloses collaboration with Molecular Targeting Technologies Inc. on selected experimental human rabies vaccine, which is supported by an NIH grant to James P McGettigan (AI081334). This work was supported by an NIH grant to James P McGettigan (AI079211). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. Funding for this writing assistance was provided by NIH grant number AI079211.