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The current European Union (EU) legislation decrees that pets entering the EU from a rabies-infected third country have to obtain a satisfactory virus-neutralizing antibody level, while those moving within the EU require only rabies vaccination as the risk of moving a rabid pet within the EU is considered negligible. A number of factors driving individual variations in dog vaccine response have been previously reported, including a high rate of vaccine failure in puppies, especially those subject to commercial transport. A total of 21 001 observations collected from dogs (2006-2012) vaccinated in compliance with the current EU regulations were statistically analysed to assess the effect of different risk factors related to rabies vaccine efficacy. Within this framework, we were able to compare the vaccination failure rate in a group of dogs entering the Italian border from EU and non-EU countries to those vaccinated in Italy prior to international travel. Our analysis identified that cross-breeds and two breed categories showed high vaccine success rates, while Beagles and Boxers were the least likely to show a successful response to vaccination (88.82% and 90.32%, respectively). Our analysis revealed diverse performances among the commercially available vaccines, in terms of serological peak windows, and marked differences according to geographical area. Of note, we found a higher vaccine failure rate in imported dogs (13.15%) than in those vaccinated in Italy (5.89%). Our findings suggest that the choice of vaccine may influence the likelihood of an animal achieving a protective serological level and that time from vaccination to sampling should be considered when interpreting serological results. A higher vaccine failure in imported compared to Italian dogs highlights the key role that border controls still have in assessing the full compliance of pet movements with EU legislation to minimize the risk of rabies being reintroduced into a disease-free area., (© 2016 The Authors. Zoonoses and Public Health Published by Blackwell Verlag GmbH.)

Currently available rabies post-exposure prophylaxis (PEP) for use in humans includes equine or human rabies immunoglobulins (RIG). The replacement of RIG with an equally or more potent and safer product is strongly encouraged due to the high costs and limited availability of existing RIG. In this study, we identified two broadly neutralizing human monoclonal antibodies that represent a valid and affordable alternative to RIG in rabies PEP. Memory B cells from four selected vaccinated donors were immortalized and monoclonal antibodies were tested for neutralizing activity and epitope specificity. Two antibodies, identified as RVC20 and RVC58 (binding to antigenic site I and III, respectively), were selected for their potency and broad-spectrum reactivity. In vitro, RVC20 and RVC58 were able to neutralize all 35 rabies virus (RABV) and 25 non-RABV lyssaviruses. They showed higher potency and breath compared to antibodies under clinical development (namely CR57, CR4098, and RAB1) and commercially available human RIG. In vivo, the RVC20-RVC58 cocktail protected Syrian hamsters from a lethal RABV challenge and did not affect the endogenous hamster post-vaccination antibody response., (© 2016 Humabs BioMed SA Published under the terms of the CC BY 4.0 license.)

Human pulmonary and subcutaneous dirofilariosis caused by Dirofilaria immitis and Dirofilaria repens are worldwide diagnosed with increasing frequency. These species are responsible for the development of benign pulmonary and subcutaneous nodules, respectively, that can be confused with lung or cutaneous cancer. The aim of the present work was to identify D. immitis and D. repens proteins differentially recognized by serum samples from individuals with human pulmonary and subcutaneous dirofilariosis, using two-dimensional electrophoresis and mass spectrometry. Twenty-three immunoreactive proteins of D. immitis and 15 of D. repens were identified. The results point to the existence of differential antigenic recognition in each species, both in the number and type of proteins recognized. Individuals with pulmonary dirofilariosis recognized, on the proteome of D. immitis, among others, different isoforms of 6 enzymes involved in glycolysis, 3 redox-related proteins with antioxidant capacity and 3 heat shock proteins. Individuals with subcutaneous dirofilariosis recognized on the proteome of D. repens only 3 glycolytic enzymes, one protein involved in redox processes and one heat shock protein. These data suggest that in cases of pulmonary dirofilariosis there exists a wider recognition of immunoreactive D. immitis proteins related to key survival processes, such as energy generation, the struggle against oxidative stress and molecular repair, than in cases of human subcutaneous dirofilariosis against D. repens. This could contribute to explain the differences described in the capacity of D. immitis and D. repens development and in the frequency of occurrence of pulmonary and subcutaneous dirofilariosis in the human host.