They request WHO to strongly recommend PrEP

vaccination for children living in areas where dog rabies is enzootic as this would support the efforts of affected countries to raise funds for PrEP implementation from national and international organizations. Administration of rabies immunoglobulin (RIG) is necessary for the success of PEP in cases of severe exposure (WHO category III [14]). Passive immunization using RIG provides immediate protection until the immune system can begin to produce its own neutralizing antibody in response to vaccination. Nevertheless, RIG is Ulixertinib clinical trial dramatically underused in rabies endemic areas. This is mainly due to the fact that highly purified RIGs, prepared from human or equine serum, are often unaffordable or in short supply and are therefore not always accessible in Asian countries. In addition, equine RIGs are often considered ‘unsafe’ due to the commercialization of locally produced products that are poorly purified or have less than adequate potency. Unfortunately, this has created a lack of trust, on the part of health care professionals and their patients, in even the most modern, highly purified equine RIG. Finally, RIG is considered by some sectors as a non-compulsory step of PEP (just “nice to have”) due to a lack of education across all sectors of society. Data on

Akt inhibitor vaccine and RIG sales in the AREB region indicates that RIGs are used in 2–10% of the PEP, while it is estimated that 48% of rabies exposures were identified as category III in the survey check completed by AREB [15]. The development of monoclonal antibodies (mAbs) may bring a solution to the current global problem of lack of accessibility to RIG. AREB members discussed the results of studies evaluating a combination of two human mAbs with rabies virus neutralizing activity, developed by Crucell and Sanofi Pasteur. The definitive added value of combining two monoclonal antibodies is their ability to bind to two distinct epitopes on the rabies virus glycoprotein, thus providing a good protection

and coverage of natural rabies virus isolates throughout the world, which it may not be possible to achieve when using only a single mAb. Phase I clinical trials conducted in the USA and in India showed that the mAb combination is safe and well tolerated when given alone or in combination with rabies vaccine. The neutralizing activity of the mAb combination was comparable to that of human rabies immunoglobulin (HRIG), which is currently considered as the gold standard [16]. Two phase II clinical trials have been performed with the mAb combination: one study in healthy adults in the USA, and another among a healthy pediatric population in the Philippines, thus confirming that this mAb combination is safe and well tolerated.