Vaccines for the Leishmaniases: Proposals for a Research Agenda

Not All Antigens Are Created Equally: Progress, Challenges, and Lessons Associated with Developing a Vaccine for Leishmaniasis

“…Escherichia coli and yeast are among the most widely used systems for the production of recombinant proteins (22)(23)(24), and bioinformatics has facilitated the production of a variety of recombinant proteins that have been investigated as Leishmania vaccine antigen candidates in animal models (15,20). Key to the use of recombinant proteins is the cost-effectiveness of production, an important consideration when modeling has shown that a cost of $2 or less per dose for a preventive vaccine would be economically advantageous over the currently available leishmaniasis treatments (25).…”

“…Besides traditional recombinant expression approaches, many antigens have also been investigated in DNA vaccines (20). VL patients possess antibodies against the hemoglobin receptor (HbR) of Leishmania, and this protein is conserved across various Leishmania strains.…”

“…Simultaneous with the progress in adjuvant technologies, advances in bioinformatics and molecular techniques have expanded the number of potential Leishmania-specific targets for use within a vaccine (17)(18)(19). A considerable number of Leishmania antigens have been tested as subunit protein or DNA vaccine candidates against various Leishmania species, but variable results have meant that very few antigens have advanced to human or canine clinical trials (20). Factors such as the Leishmania source of the target gene, the Leishmania species involved in the challenge, the quantity of antigen/vector used, and the frequency and numbers of immunizations all impact our ability to interpret the data beyond their immediate application.…”

Liposomal adjuvant development for leishmaniasis vaccines

“…Development of the Leishmania vaccine using whole killed parasites have been attempted since the 1940s 6 and also reached clinical trials, but with limited efficacy. [7][8][9] In terms of secondgeneration vaccines, despite the proposal of several recombinant proteins or DNA molecules, only Leish-111f, Leish-F2, and Leish-F3 reached clinical trials. These vaccines contained recombinant polyproteins and were formulated with monophosphoryl lipid A (MPL) in an oil/water stable emulsion using squalene.…”

Candidatos a leishmanicidas, antichagásicos e tuberculostáticos: estudo da síntese de fármacos dirigidos de hidroximetilnitrofural com manana para liberação específica em macrófagos

“…Nesta, os parasitas apresentam acentuado tropismo pelo SFM do baço, fígado, medula óssea e tecidos linfóides, o que pode gerar hipertrofia e hiperplasia do sistema macrofágico das vísceras, ocorrendo espleno e hepatomegalias e alterações na medula óssea (REY, 2001;NEVES, 2000;HARHAY et al, 2011, WHO, 2013b Com relação às vacinas para a referida patologia, existe um grande número de pesquisas nesta área, muitas com resultados promissores, porém, ainda não há vacinas disponíveis. Observa-se que a leishmaniose ainda se encontra em expansão no País, devido às mudanças ambientais, migração de indivíduos não imunes às áreas endêmicas, falha terapêutica e crescimento de cepas resistentes ao tratamento (MAIA et al, 2007;LINDOSO, LINDOSO, 2009;MITROPOULOS, KONIDAS, DURKIN-KONIDAS, 2010;COSTA et al, 2011 (WHO, 2009a(WHO, , 2009d(WHO, , 2011b(WHO, , 2012a A transmissão do bacilo (Figura 15) ocorre quando um indivíduo suscetível entra em contato, por meio de suas vias aéreas, com gotículas de aerossol, contendo o bacilo, geradas através da tosse de um indivíduo que apresenta doença ativa. A partir do momento em que o microrganismo se encontra nos alvéolos pulmonares, este é fagocitado por macrófagos alveolares e, em seu interior, multiplica-se dentro de fagossomos únicos, que não se fundem aos lisossomos.…”