Synergizing vaccinations with therapeutics for measles eradication

Abstract

Introduction: The measles virus is a major human pathogen responsible for approximately 150,000 deaths annually. The disease is vaccine preventable and eradication of the virus is considered feasible, in principle. However, a herd immunity exceeding 95% is required to prevent sporadic viral outbreaks in a population. Declining disease prevalence, combined with public anxiety over the vaccination's safety, has led to increased vaccine refusal, especially in Europe. This has led to the resurgence of measles in some areas.

Areas covered: This article discusses whether synergizing effective measles therapeutics with the measles vaccination could contribute to finally eradicating measles. The authors identify key elements in a desirable drug profile and review current disease management strategies and the state of experimental inhibitor candidates. The authors also evaluate the risk associated with viral escape from inhibition, and consider the potential of measles therapeutics in the management of persistent central nervous system (CNS) viral infection. Finally, the authors contemplate the possible impact of therapeutics in controlling the threat imposed by closely related zoonotic pathogens of the same genus as measles.

Expert opinion: Efficacious therapeutics used for post-exposure prophylaxis of high-risk social contacts of confirmed index cases may aid measles eradication by closing herd immunity gaps; this is due to vaccine refusal or failure in populations with overall good vaccination coverage. The envisioned primarily prophylactic application of measles therapeutics to a predominantly pediatric and/or adolescent population, dictates the drug profile. It also has to be safe and efficacious, orally available, shelf-stable at ambient temperature and amenable to cost-effective manufacturing.

Figure 1

Schematic representation of an MeV particle. The viral envelope (purple double line) is densely coated by viral attachment and fusion glycoprotein oligomers, which in a concerted action mediate fusion of the envelope with cellular membranes for viral entry upon receptor binding. Short cytosolic domains of the envelope glycoproteins are thought to interact with the matrix protein layer, which also stands in contact with the viral genome and organizes particle assembly. The MeV genome consists of a single non-segmented RNA strand of negative polarity that is tightly encapsidated by the N protein in a ribonucleoprotein complex. The large (L) subunit of the viral RNA-dependent RNA-polymerase complex is together with the P protein polymerase cofactor responsible for genome replication and the synthesis of viral mRNAs.

Figure 2

Estimated number of global measles deaths in the 2000 to 2011 period. Source: WHO.