O desenvolvimento de vacinas contra a raiva tão eficientes quanto as atuais ainda é considerado importante para a profilaxia dessa doença devido ao alto número de mortes por ano no mundo. Este trabalho mostra dois sistemas para a expressão recombinante do principal antígeno da raiva, a glicoproteína viral (RVGP): células Schneider 2 de Drosophila melanogaster estavelmente transfectadas (S2 rRVGP) e vírus Semliki Forest (SFV) carregando o RNA da RVGP (SFVRVGP). Ensaios de purificação por cromatografia de afinidade, da rRVGP de S2 rRVGP produzida em biorreator, demonstraram resultados promissores para o isolamento de monômeros da rRVGP. Para os estudos de imunogenicidade, camundongos foram vacinados com rRVGP de S2 rRVGP e SFV-RVGP. Dosagem de anticorpos anti-glicoproteína do vírus da raiva, neutralizantes, IgG1 e IgG2a, e citocinas demonstraram que o SFV-RVGP induziu predominantemente uma resposta imune do tipo celular e que os dois vetores foram capazes de expressar uma rRVGP imunogênica, apresentando um potencial uso clínico (veterinário e humano). / The development of new and equally efficient rabies vaccines is still considered important to the prophylaxis of the disease, which is responsible for many deaths per year worldwide. This work used two systems for recombinant expression of the major rabies antigen, the viral glycoprotein (RVGP): stably transfected Drosophila melanogaster Schneider 2 cells (S2 rRVGP) and Semliki Forest Virus (SFV) carrying the RNA of RVGP (SFV-RVGP). Purification assays of the rRVGP by metal ion affinity chromatography, from S2 rRVGP cells produced in bioreactor, showed promising results for rRVGP monomers isolation. Analysis of antibodies anti-rabies virus glycoprotein, neutralizing, IgG1 and IgG2a, and citokines showed that the SFV-RVGP induced predominantly a cellular immune response, and both vectors were capable of expressing an immunogenic rRVGP, what reinforces potential clinical applications (veterinary or human).

Este estudo buscou estabelecer um sistema de produção de pps, contendo a proteína Gag do MLV para formação da cápside, as glicoproteínas de membrana E1 e E2 do HCV carregando o RNA da glicoproteína do vírus da raiva - RVGP (ppHCV-RVGP). Para gerar ppHCV-RVGP, células HEK293-T foram co-transfectadas com 3 vetores, utilizando lipofectamina e eletroporação. As ppHCV-RVGP foram coletadas do sobrenadante 48 h p.t e quantificadas por qRT-PCR foram obtidas 300 cópias de RNA/μL, para ambos os métodos de co-transfecção. Células Huh 7 foram infectadas e a expressão da RVGP foi analisada 48 h p.i. por ELISA e imunofluorescência indireta (IFI). Estes imunoensaios mostraram a baixa expressão da proteína RVGP. Realizamos ensaios de qRT-PCR para detectar a adesão e entrada da ppHCV-RVGP e verificou-se que a estas foram ineficientes. Realizamos western blotting para analisar a expressão das proteínas necessárias para a formação das ppHCV, este mostrou a produção da proteína Gag e a incorporação das proteínas de membrana, porém a glicoproteína E2 não foi incorporada eficientemente na membrana da ppHCV. Concluímos que o sistema de pseudopartículas virais foi eficiente para transportar o RNA-RVGP, porém não foi capaz de infectar eficientemente células Huh 7. / The aim of this study was to establish a system for the production of pps, containing the protein Gag of MLV to form the capsid, the glycoproteins membrane E1 and E2 of HCV and carrying the RNA of glycoprotein of rabies virus - RVGP (ppHCV-RVGP). To produce ppHCV-RVGP, HEK293-T cells were co-transfected with 3 vectors using lipofectamine and electroporation. The pps were harvested from the supernatant 48 h p.t. and quantificated by qRT-PCR and resulted in 300 copies of RNA/μL, to both methods of co-transfection. Huh 7 cells were infected and RVGP expression was analyzed 48 hours after by ELISA and indirect immunofluorescence (IFI) assays. These immunoassays showed a low expression of RVGP. Others assays of qRT-PCR conducted to detect the adhesion and entry of ppHCV-RVGP showed that this process was inefficient. We performed western blotting assays to analyze the proteins required to form the ppHCV. Western blotting assays that the production of Gag protein and incorporation of glycoproteins were successful, however E2 glycoprotein has not been incorporated efficiently on ppHCV membrane. In conclusion, the system of virus pseudoparticles was efficient in carrying the RNA-RGVP, although was not able to efficiently infect Huh 7 cells.

Submitted by Ubirajara Cruz (ubirajara.cruz@gmail.com) on 2017-06-09T14:44:44Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Roberta Silva Silveira da Mota.pdf: 5877448 bytes, checksum: e1775066c7225b12cb1987370c762960 (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2017-06-09T14:56:22Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Roberta Silva Silveira da Mota.pdf: 5877448 bytes, checksum: e1775066c7225b12cb1987370c762960 (MD5) / Made available in DSpace on 2017-06-09T14:56:22Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Roberta Silva Silveira da Mota.pdf: 5877448 bytes, checksum: e1775066c7225b12cb1987370c762960 (MD5) Previous issue date: 2016-01-20 / Sem bolsa / As ações do Programa Nacional de Profilaxia da Raiva (PNPR) levaram a uma importante redução de casos humanos e a um controle do ciclo urbano em cães e gatos, nas diferentes regiões do país, contudo a raiva continua sendo um grave problema de Saúde Pública no Brasil e no mundo. O Rio Grande do Sul (RS) apresenta status de área controlada para o ciclo urbano há cerca de 20 anos, sem circulação de variantes caninas e sem o registro de casos humanos. Entretanto, verifica-se a manutenção de ciclos silvestres representados por quirópteros, inclusive em áreas urbanas. Este estudo foi organizado em dois sub-projetos. O primeiro teve por objetivo conhecer o comportamento do ciclo aéreo da doença na área urbana do município de Pelotas, RS, utilizando técnicas de diagnóstico padrão ouro, sorológicas e de biologia molecular, e desta forma, caracterizar a infecção pelo vírus da raiva em morcegos. O segundo subprojeto, a partir do entendimento de que um importante pilar da prevenção da doença em humanos consiste na profilaxia pré-exposição dos grupos de risco, buscou descrever o perfil dos atendimentos para profilaxia antirrábica pré-exposição (PArPE) humana realizados pelas Secretarias Municipais de Saúde, conforme metodologia do PNPR do Ministério da Saúde (MS), no Estado, através de um estudo descritivo a partir de dados coletados no Sistema Nacional de Agravos de Notificação (SINAN Net) do MS. Foram coletados 238 morcegos e submetidos a diagnóstico rábico padrão e técnicas complementares. Daqueles em que se pode recuperar sangue, foi realizada sorologia. A prevalência de vírus rábico foi de 3,60%, confirmados por IFD, RT-PCR do cérebro e da glândula salivar. A prevalência de anticorpos através do teste rápido de inibição de foco da fluorescência (RFFIT) foi 23,27% enquanto que no microteste simplificado de inibição da fluorescência (SFIMT) foi de 51,5%. Por outro lado, foi demonstrado que há diversas inconsistências no uso da PArPE no RS, com uso de tratamento em muitas situações em que não haveria a indicação e, ao mesmo tempo, mantendo pessoas em situação de risco não protegidas. A implicação destes achados é discutida nos dois artigos. / The National Rabies Prophylaxis Program (PNPR) actions led to an important reduction of human cases and certain control of urban cycle in cats and dogs, in different regions of the country. However, rabies still is a serious Public Health issue in Brazil and in the world. The state of Rio Grande do Sul (RS) is an area where the urban rabies cycle is considered controlled for about 20 years, having no canine virus variants circulation and no human cases registered. However, the maintenance of chiropters wild cycles still is detected, including among urban areas. The research was divided in two sub-projects. The first one aimed studying the disease's aerial cycle in the city of Pelotas, RS, through gold standard diagnosis, molecular biology and serological techniques, and then establishing the rabies virus infection in bats. The second subproject, based on the understanding that the pre-exposure prophylaxis in risk groups is the cornerstone of human rabies prevention, sought describing the human anti-rabies pre-exposure prophylaxis intervention (PArPE) profile, performed in State public health secretariats, according the methodology presented in the Ministry of Health's National Human Rabies Prophylaxis Program, through a descriptive study using data collected by the Ministry of Health's National Notification of Diseases System (SINAN Net). To that end, 238 bats were collected and put through standard rabies diagnosis and complementary techniques. Serology was performed in those which blood was found. Rabies virus prevalence was 3.60%, confirmed through DFA test, and brain and salivary gland RT-PCR. Antibodies prevalence through Rapid fluorescent focus inhibition test (RFFIT) was 23.27%, and 51.5% through Simplified fluorescent inhibition microtest (SFIMT). On the other hand, it was shown that the PArPE application in RS is inconsistent, where the treatment has been used in many situations in which it wouldn't be indicated, and, at the same time, leaving people in risk situations unprotected. These results implications are discussed in both articles.

Made available in DSpace on 2014-06-11T19:27:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-02-08Bitstream added on 2014-06-13T20:08:21Z : No. of bitstreams: 1 frias_dfr_me_jabo.pdf: 647256 bytes, checksum: 56a7d9c80f805156699c273aa7a7a23c (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Um elevado número de tratamentos anti-rábicos profiláticos são efetuados, anualmente, em pessoas envolvidas em agravos com animais. Assim, este trabalho objetivou avaliar os registros e a conduta de profilaxia anti-rábica humana no Município de Jaboticabal, de 2000 a 2006, analisando as informações das fichas de atendimento e a distribuição geográfica dos agravos. Os dados foram tabulados em Excel e analisados com softwares EpiInfo e MapInfo. Também foi calculado o custo direto com as vacinas anti-rábicas humanas. Em 3056 fichas analisadas, computou-se um agravo para cada 160 habitantes, com maior ocorrência em residências e nos bairros da região central da cidade, e incremento de casos nos meses de janeiro, julho, agosto e dezembro. A faixa etária mais atingida foi de 0 a 15 anos, destacando-se o sexo masculino. Com relação à espécie animal envolvida, a canina foi a responsável pela maioria dos agravos, sendo 67,5% dos cães e 22,2% dos gatos declarados vacinados; os cães estavam sadios em 77,8% dos casos. Das pessoas agredidas, 81,6% receberam profilaxia pós-exposição, num total de 7.108 doses de vacina e a um custo aproximado de R$179.105,14. A análise detalhada dos dados, aliada ao fato de Jaboticabal ser considerada região controlada para a raiva, permitem questionar que 1.720 pessoas podem ter recebido vacina sem necessidade. Uma maior atenção deve ser dispensada aos registros de atendimento a agravos por animais, e uma análise acurada e mais criteriosa destes deve ser feita para que os tratamentos sejam instituídos adequadamente. Como a maioria dos acidentes ocorre em residências, portanto com cães e gatos domiciliados e vacinados, recomendam-se programas educativos para promoverem a posse responsável e o conhecimento dos cuidados que as pessoas devem ter com seus animais de estimação. / A large number of rabies post-exposure treatment is annually given to humans attacked by animals. This study was aimed to evaluate the records and the conduct of rabies prophylaxis in humans, in the municipality of Jaboticabal, from 2000 to 2006, through the analysis of patients´ records and geographic distribution of the accidents. The data were arranged in Excel® spreadsheets and were further analysed by EpiInfo® and MapInfo®. Also, the direct costs of given vaccines were calculated. From 3,056 patient´s cards, it was observed 1 animal attack per 160 inhabitants, with higher occurence in residences, central neighborhoods and concentration of attacks in the months of January, July, August and December. The most affected age group was that of 0-15 years old, with predominance in males. As to animal species, dogs were responsible for causing the majority of accidents. 67.5% of dogs and 22.2% of cats had already been vaccinated before attacking. In 77.8% of occurences, the dogs were healthy. As to attacked humans, 81.6% of them received post-exposure prophylaxis, totalizing 7,108 antirabies vaccine doses at an approximate cost of R$179.105,14. Thorough data analysis and the fact that Jaboticabal lies in a rabies controlled region allow to question the administration of post-exposure vaccination in 1,720 persons. More attention should be payed to filling out and interpreting patient´s records correctly, so that treatments can be properly established. As most attacks happen in the residences, where cats and dogs are usually domiciled and vaccinated, it is essencial to develop educational programs that promote responsible pet ownership and adequate pet handling and care.

O desenvolvimento de vacinas contra a raiva tão eficientes quanto as atuais ainda é considerado importante para a profilaxia dessa doença devido ao alto número de mortes por ano no mundo. Este trabalho mostra dois sistemas para a expressão recombinante do principal antígeno da raiva, a glicoproteína viral (RVGP): células Schneider 2 de Drosophila melanogaster estavelmente transfectadas (S2 rRVGP) e vírus Semliki Forest (SFV) carregando o RNA da RVGP (SFVRVGP). Ensaios de purificação por cromatografia de afinidade, da rRVGP de S2 rRVGP produzida em biorreator, demonstraram resultados promissores para o isolamento de monômeros da rRVGP. Para os estudos de imunogenicidade, camundongos foram vacinados com rRVGP de S2 rRVGP e SFV-RVGP. Dosagem de anticorpos anti-glicoproteína do vírus da raiva, neutralizantes, IgG1 e IgG2a, e citocinas demonstraram que o SFV-RVGP induziu predominantemente uma resposta imune do tipo celular e que os dois vetores foram capazes de expressar uma rRVGP imunogênica, apresentando um potencial uso clínico (veterinário e humano). / The development of new and equally efficient rabies vaccines is still considered important to the prophylaxis of the disease, which is responsible for many deaths per year worldwide. This work used two systems for recombinant expression of the major rabies antigen, the viral glycoprotein (RVGP): stably transfected Drosophila melanogaster Schneider 2 cells (S2 rRVGP) and Semliki Forest Virus (SFV) carrying the RNA of RVGP (SFV-RVGP). Purification assays of the rRVGP by metal ion affinity chromatography, from S2 rRVGP cells produced in bioreactor, showed promising results for rRVGP monomers isolation. Analysis of antibodies anti-rabies virus glycoprotein, neutralizing, IgG1 and IgG2a, and citokines showed that the SFV-RVGP induced predominantly a cellular immune response, and both vectors were capable of expressing an immunogenic rRVGP, what reinforces potential clinical applications (veterinary or human).

Este estudo buscou estabelecer um sistema de produção de pps, contendo a proteína Gag do MLV para formação da cápside, as glicoproteínas de membrana E1 e E2 do HCV carregando o RNA da glicoproteína do vírus da raiva - RVGP (ppHCV-RVGP). Para gerar ppHCV-RVGP, células HEK293-T foram co-transfectadas com 3 vetores, utilizando lipofectamina e eletroporação. As ppHCV-RVGP foram coletadas do sobrenadante 48 h p.t e quantificadas por qRT-PCR foram obtidas 300 cópias de RNA/μL, para ambos os métodos de co-transfecção. Células Huh 7 foram infectadas e a expressão da RVGP foi analisada 48 h p.i. por ELISA e imunofluorescência indireta (IFI). Estes imunoensaios mostraram a baixa expressão da proteína RVGP. Realizamos ensaios de qRT-PCR para detectar a adesão e entrada da ppHCV-RVGP e verificou-se que a estas foram ineficientes. Realizamos western blotting para analisar a expressão das proteínas necessárias para a formação das ppHCV, este mostrou a produção da proteína Gag e a incorporação das proteínas de membrana, porém a glicoproteína E2 não foi incorporada eficientemente na membrana da ppHCV. Concluímos que o sistema de pseudopartículas virais foi eficiente para transportar o RNA-RVGP, porém não foi capaz de infectar eficientemente células Huh 7. / The aim of this study was to establish a system for the production of pps, containing the protein Gag of MLV to form the capsid, the glycoproteins membrane E1 and E2 of HCV and carrying the RNA of glycoprotein of rabies virus - RVGP (ppHCV-RVGP). To produce ppHCV-RVGP, HEK293-T cells were co-transfected with 3 vectors using lipofectamine and electroporation. The pps were harvested from the supernatant 48 h p.t. and quantificated by qRT-PCR and resulted in 300 copies of RNA/μL, to both methods of co-transfection. Huh 7 cells were infected and RVGP expression was analyzed 48 hours after by ELISA and indirect immunofluorescence (IFI) assays. These immunoassays showed a low expression of RVGP. Others assays of qRT-PCR conducted to detect the adhesion and entry of ppHCV-RVGP showed that this process was inefficient. We performed western blotting assays to analyze the proteins required to form the ppHCV. Western blotting assays that the production of Gag protein and incorporation of glycoproteins were successful, however E2 glycoprotein has not been incorporated efficiently on ppHCV membrane. In conclusion, the system of virus pseudoparticles was efficient in carrying the RNA-RGVP, although was not able to efficiently infect Huh 7 cells.

Master of Science / Department of Biology / Samantha Wisely / As human populations increase world-wide, land use and land cover are altered to support the rapid anthropogenic expansion. These landscape alterations influence patterns of zoonotic infectious disease emergence and propagation. It is therefore becoming increasingly important to study emerging and re-emerging diseases to predict and manage for future epidemics. Studies of directly-transmitted infectious diseases should consider three components of disease epidemiology: characteristics of the pathogen, ecology of the host, and habitat configuration of the underlying landscape. I studied the influence of both the host ecology of the striped skunk (Mephitis mephitis) and the alteration of the underlying landscape on the epidemiology of rabies virus in the Flint Hills of Kansas. This tall-grass prairie is experiencing woody expansion due to anthropogenic disturbance, altering the landscape on which the rabies virus emerges and spreads. We first studied the behavioral and social ecology of the striped skunk using field and genetic methods. We concluded that 1) striped skunks reached high population densities in anthropogenically disturbed habitats, 2) these individuals were not closely related, and 3) contact rates could be influenced by temperature. Using habitat-specific skunk densities from this initial study, we created spatially-explicit contact networks of skunk populations across the Upper Kansas River Watershed and simulated the emergence and spread of rabies through the system. This modeling approach revealed a threshold of forest habitat beyond which striped skunks became increasingly connected and the rabies virus reached greater extents across the landscape. Based on these findings we recommend fire regimes and land cover alterations to reduce woody encroachment across the Flint Hills and to avoid future disease epidemics in the region.

Master of Public Health / Department of Diagnostic Medicine and Pathobiology / M. M. Chengappa / Rabies is the most deadly disease on earth and has a 99.9% human fatality rate. Rabies kills 61,000 humans annually and results in an economic burden of $124 billion USD annually. Each day 3.3 million people live with the risk of rabies. It is estimated that 95% of human rabies cases are a result of coming in contact with an infected canine, majority of these cases being children 15 years and younger. It is estimated that 1 person every 8 minutes dies of rabies. Rabies is a highly neurotropic disease which attacks the brain and central nervous system. Once clinical symptoms are presented, death is invariably the outcome as no cure exists for rabies. Rabies is 100% preventable in humans by proper wound management and proper administration of prophylaxis. Rabies can be adequately controlled in animal populations by contraception and animal rabies vaccine efforts. Whilst it is known that rabies can be prevented in humans and controlled in animal populations, further scientific efforts are still warranted to fully understand this deadly virus so that a cure can one day be discovered. As human and animal populations continue to grow, so does the cost and burden of this horrific disease. As a result, the importance of prophylaxis and passive immunity are critical in the event of medically managing an exposure, and preventing exposures. The World Health Organization has defined global recommendations for individuals and animals who have received prophylaxis to be adequately protected. Measuring this protection is performed using a variety of approved testing methodologies, virus-neutralizing assays and antigen-binding assays. Whilst the WHO recommendations were defined from clinical studies performed with virus-neutralizing assays, the assumption that these recommendations are suitable for the antigen-binding assays is inaccurate. The testing methodologies, virus-neutralization and antigen-binding, share similarities, as they are measuring an immune response to the rabies virus. However; enough differing characteristics are presented such that exact comparisons cannot be made. Establishing the same standards and recommendations for both testing methodologies will never be sufficient.

<p>The mouth, throat, and face contain numerous muscles that participate in a large variety of orofacial behaviors. The jaw and tongue can move independently, and thus require a high degree of coordination among the muscles that move them to prevent self-injury. However, different orofacial behaviors require distinct patterns of coordination between these muscles. The method through which motor control circuitry might coordinate this activity has yet to be determined. Electrophysiological, immunohistochemical, and retrograde tracing studies have attempted to identify populations of premotor neurons which directly send information to orofacial motoneurons in an effort to identify sources of coordination. Yet these studies have not provided a complete picture of the population of neurons which monosynaptically connect to jaw and tongue motoneurons. Additionally, while many of these studies have suggested that premotor neurons projecting to multiple motor pools may play a role in coordination of orofacial muscles, no clear functional roles for these neurons in the coordination of natural orofacial movements has been identified.</p><p>In this dissertation, I took advantage of the recently developed monosynaptic rabies virus to trace the premotor circuits for the jaw-closing masseter muscle and tongue-protruding genioglossus muscle in the neonatal mouse, uncovering novel premotor inputs in the brainstem. Furthermore, these studies identified a set of neurons which form boutons onto motor neurons in multiple motor pools, providing a premotor substrate for orofacial coordination. I then combined a retrogradely traveling lentivirus with a split-intein mediated split-Cre recombinase system to isolate and manipulate a population of neurons which project to both left and right jaw-closing motor nuclei. I found that these bilaterally projecting neurons also innervate multiple other orofacial motor nuclei, premotor regions, and midbrain regions implicated in motor control. I anatomically and physiologically characterized these neurons and used optogenetic and chemicogenetic approaches to assess their role in natural jaw-closing behavior, specifically with reference to bilateral masseter muscle electromyogram (EMG) activity. These studies identified a population of bilaterally projecting neurons in the supratrigeminal nucleus as essential for maintenance of an appropriate level of masseter activation during natural chewing behavior in the freely moving mouse. Moreover, these studies uncovered two distinct roles of supratrigeminal bilaterally projecting neurons in bilaterally synchronized activation of masseter muscles, and active balancing of bilateral masseter muscle tone against an excitatory input. Together, these studies identify neurons which project to multiple motor nuclei as a mechanism by which the brain coordinates orofacial muscles during natural behavior.</p> / Dissertation

Orientador: Cáris Maroni Nunes / Coorientador: Luzia Helena Queiroz / Banca: Adolorata Aparecida Bianco Carvalho / Banca: Rafael Silva Cipriano / Resumo: A raiva é uma zoonose globalmente distribuída que apresenta alta letalidade, constituindo grande problema em saúde pública. A persistência do vírus da raiva nas populações é mantida devido sua capacidade de se replicar em diversas espécies de mamíferos, incluindo os humanos. O controle da raiva urbana tem se baseado na vacinação de cães e gatos, reservatórios importantes no ciclo urbano, bem como no atendimento de indivíduos após exposição ao vírus da raiva. Adicionalmente, a profilaxia pré-exposição (PrPE) tem sido aplicada em indivíduos que podem ser expostos à infecção, por atividade ocupacional. Objetivando proteger os estudantes ingressantes do Curso de Medicina Veterinária, grupo de risco em potencial para a raiva, a Faculdade de Medicina Veterinária (FMVA) da Unesp, Câmpus Araçatuba, promove anualmente a vacinação em esquema PrPE, seguida de avaliação sorológica, a fim de habituá-los a anualmente verificarem a resposta de anticorpos. Assim, a presente pesquisa teve como objetivo avaliar, por meio de levantamento de dados de PrPE dos arquivos do Serviço de Vigilância Epidemiológica da Secretaria de Saúde da Prefeitura Municipal de Araçatuba, SP, Brasil a adesão à PrPE, a proteção conferida e a dinâmica dos anticorpos (IgG) neutralizantes contra o vírus da raiva, nos estudantes da FMVA durante o período de 2000 a 2017. Foram avaliados 2.404 registros, 86,4% dos quais apresentaram título protetor contra o vírus da raiva (≥0,5UI/mL). A PrPE teve boa adesão pelos estudantes... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Rabies is a globally distributed zoonosis that shows high lethality and is also a major public health problem. Persistence of rabies virus in populations is maintained due to its ability to replicate in several mammals species, including humans. Rabies control has been based on dogs and cats' vaccination, the most important reservoirs in the urban cycle, as well as on the treatment of individuals after exposure to the rabies virus. In addition, pre-exposure prophylaxis (PEPr) has been applied in individuals who might be exposed to infection due to their occupational activities. In order to protect the incoming students of the veterinary medicine course, a group of potential risk for rabies, the School of Veterinary Medicine (FMVA) of Unesp, Araçatuba, SP, Brazil, promotes annual vaccination in a PEPr scheme, followed by a serological evaluation, in order to habituate them to annually check their antibody response. Thus, by analyzing the PEPr data from the archives of the Epidemiological Surveillance Service of the Health Department of Araçatuba, SP, Brazil, during the period from 2000 to 2017, the present study aimed at evaluating the adhesion of the students to the rabies PEPr, the protection conferred by it and the dynamics of the neutralizing IgG antibodies against rabies virus. A total of 2,404 records were evaluated, 86.4% of which presented protective titers against rabies (≥0.5 IU/mL). PEPr had good adhesion by the students, has proved to be effective for generating an... (Complete abstract click electronic access below) / Mestre