Vacunas contra el virus chikungunya: avances y perspectivas

El virus chikungunya (CHIKV) es un alfavirus cuya infección provoca una enfermedad caracterizada principalmente por fiebre y dolores articulares/musculares. Entre 25-50% de las infecciones se presentan con enfermedad crónica que puede durar de meses a años. El primer brote de CHIKV en Paraguay corresponde al año 2015, siendo el último en el año 2022/2023. Diversos candidatos vacunales contra CHIKV se encuentran en diferentes etapas de desarrollo, e incluso recientemente (noviembre/2023) fue aprobada la primera vacuna contra CHIKV llamada VLA1553 (Ixchiq). Adicionalmente, al menos 30 candidatos vacunales se encuentran en ensayos preclínicos/clínicos. Con la aprobación de la primera vacuna contra CHIKV y la posibilidad de otras que lleguen al mercado prontamente, debido al estado avanzado de otros candidatos vacunales, se abrirá un nuevo escenario en esta enfermedad. Se espera que la introducción de vacunas efectivas genere un avance importante para la prevención de esta enfermedad, disminuyendo los casos agudos y los efectos crónicos de la infección por el virus. En este trabajo de revisión se analiza el avance de las vacunas contra CHIKV, además de examinar los desafíos de vigilancia epidemiológica que plantean la introducción de estas vacunas.

Chikungunya virus (CHIKV) is an alphavirus that causes an illness characterized mainly by fever and joint/muscle pain. Between 25-50% of infections present with chronic diseases that can last from months to years. The first outbreak of CHIKV in Paraguay occurred in 2015, with the last outbreak occurring in 2022/2023. Several vaccine candidates against CHIKV are in different stages of development, and even recently (November/2023), the first vaccine against CHIKV, called VLA1553 (Ixchiq), was approved. In addition, at least 30 vaccine candidates are available for preclinical and clinical trials. With the approval of the first vaccine against CHIKV and the possibility of others coming to the market soon, due to the advanced status of other vaccine candidates, a new scenario will open for this disease. The introduction of effective vaccines is expected to generate an important advance in the prevention of this disease, reducing acute cases and the chronic effects of viral infection. This review analyzes the progress of CHIKV vaccines and examines the epidemiological surveillance challenges posed by the introduction of these vaccines.

Protocolo de Revisão de Escopo: a experiência internacional no desenvolvimento e produção de vacina para COVID-19 / Protocol scoping review: the international experience in vaccine development and production for COVID-19

Este protocolo teve como objetivo estruturar as etapas de elaboração de um Scoping Review que pretende estudar as experiências de desenvolvimento e produção de vacinas em 5 países selecionados, comparando com o Brasil. Sendo assim, a introdução buscou contextualizar a questão de desenvolvimento e produção de vacinas no mundo. Posteriormente, foi apresentado o método do trabalho que, neste caso perpassa por uma explanação da escolha prévia dos 5 países selecionados, além de uma busca em 5 repositórios, seguida de busca manual. A pergunta de pesquisa e as palavras chaves foram apresentadas em conjunto com descrição dos critérios de inclusão e exclusão, que levaram a uma seleção final de 25 documentos completos. Por fim, foram apresentados os resultados esperados, quanto ao que se espera encontrar na análise de atores e ações realizadas nos países investigados

This protocol aimed to structure the steps of a Scoping Review that intends to study the experiences of vaccine development and production in 5 selected countries, comparing with Brazil. Thus, the introduction sought to contextualize the issue of vaccine development and production in the world. Afterwards, the method of the work was presented, which in this case involves an explanation of the previous choice of the 5 selected countries, besides a search in 5 repositories, followed by a manual search. The research question and the key words were presented together with a narrative of the inclusion and exclusion criteria, which led to a total selection of 25 full documents. Finally, the expected results were presented, which indicates what is expected to be found in the analysis of actors and actions taken in the countries in question

Single cell RNA sequencing technology applicated for drug discovery / 药学学报

Single cell RNA sequencing (scRNA-seq) is an advanced technology to study the transcriptome information at the single cell level. The application of this technology can attribute to analyze the heterogeneous map of cells in the process of disease development, and precisely identify the specific cell subsets that are responsive to pharmacological therapy. Currently, scRNA-seq technology has been widely applied in the field of drug research, including studies on therapeutic targets, drug-induced adverse reactions, drug resistance and vaccine. This work reviews the application of scRNA-seq technology in drug discovery, which offers a scientific basis for personalized and accurate medication therapy.

Application of quantitative pharmacology in vaccine research and development: overview and prospect / 中国临床药理学与治疗学

This article introduces the mechanism including antigen presentation, adjuvant, lymphatic system and the characteristics of vaccine, and then summarizes the key applications of core pharmacometrics approaches including QSP, PK/PD, dose response analysis, MBMA, in dose-response, preclinical and clinical translation, and correlation between biomarkers and efficacy of vaccines. It is expected that the successful application of model informed drug development can promote model informed vaccine development so that pharmacometrics makes its due contributions to the development of safer, more effective and more controllable vaccine products.

Innovation-driven trend shaping COVID-19 vaccine development in China / 医学前沿

Confronted with the Coronavirus disease 2019 (COVID-19) pandemic, China has become an asset in tackling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and mutation, with several innovative platforms, which provides various technical means in this persisting combat. Derived from collaborated researches, vaccines based on the spike protein of SARS-CoV-2 or inactivated whole virus are a cornerstone of the public health response to COVID-19. Herein, we outline representative vaccines in multiple routes, while the merits and plights of the existing vaccine strategies are also summarized. Likewise, new technologies may provide more potent or broader immunity and will contribute to fight against hypermutated SARS-CoV-2 variants. All in all, with the ultimate aim of delivering robust and durable protection that is resilient to emerging infectious disease, alongside the traditional routes, the discovery of innovative approach to developing effective vaccines based on virus properties remains our top priority.

Clinical trials of COVID-19 vaccine development: a global overview / Ensaios clínicos de desenvolvimento de vacinas contra a COVID-19: uma visão global / Ensayos clínicos de desarrollo de vacunas contra el COVID-19: una descripción general

Abstract: This study aims to report analyses regarding the global distribution of institutions involved in clinical trials of COVID-19 vaccines throughout February 2022. We retrieved global data from the World Health Organization report on vaccine development. These data allowed us to identify project institutions and plot their geographic coordinates. We produced a georeferenced map using an R programming environment and, based on the geographical location of vaccine developers, we analyzed the subcontinental distribution of clinical trials and the nature of the vaccines. Regionally, South-Southeast Asian countries carried out more clinical trials than any other region, proportionally, although this happened solely for mature technologies. Few trials were under implementation in Latin America and Africa. Our findings confirm previous studies on the regional concentration in the development of technology. However, our contribution lies in showing these phenomena for COVID-19 vaccines in specific subcontinents and technologies, at a country level. Our data underscores which subcontinents perform very few clinical trials for COVID-19 and seem to be ill-prepared for future disease outbreaks, and if these become epidemics or even pandemics and require domestic vaccine development or production. We also consider the case of Brazil, which did not finish the complete cycle of COVID-19 vaccine development in the indicated period; but, with favorable policies, it has potential to engage further in COVID-19 vaccine technology.

Resumo: O objetivo desta comunicação é relatar análises sobre a distribuição global das instituições envolvidas em ensaios clínicos relacionados às vacinas de COVID-19 até fevereiro de 2022. Obtivemos dados globais da Organização Mundial da Saúde sobre o desenvolvimento de vacinas. Isso nos permitiu identificar as instituições de projetos e traçar as suas coordenadas geográficas. Produzimos um mapa georreferenciado usando a linguagem de programação R e, a partir da localização geográfica dos desenvolvedores de vacinas, analisamos a distribuição subcontinental dos ensaios clínicos e a natureza das vacinas testadas. Regionalmente, os países do Sul-Sudeste Asiático realizaram proporcionalmente mais ensaios clínicos do que qualquer outra região, embora isso tenha acontecido para tecnologias maduras. Poucos ensaios estavam em fase de implementação na América Latina e na África. Nossos achados confirmam estudos anteriores sobre a concentração regional no desenvolvimento de tecnologia. No entanto, a nossa contribuição está em demonstrar esses fenômenos para vacinas contra a COVID-19 em subcontinentes e tecnologias específicas em nível nacional. Os nossos dados ressaltam quais subcontinentes realizam muito poucos ensaios clínicos para COVID-19 e parecem estar mal preparados para futuros surtos de doenças e no caso de esses se tornarem epidemias ou mesmo pandemias e exigirem desenvolvimento ou produção de vacinas domésticas. Consideramos também o caso do Brasil, que não encerrou o ciclo completo de desenvolvimento da vacina contra a COVID-19 no período indicado; mas, com políticas favoráveis, tem potencial para se envolver ainda mais na tecnologia de vacinas contra a COVID-19.

Resumen: El propósito de este texto es reportar un análisis sobre la distribución global de instituciones involucradas en ensayos clínicos relacionados con vacunas del COVID-19 hasta febrero de 2022. Se recogieron datos globales de la Organización Mundial de la Salud sobre el desarrollo de vacunas; lo que se pudo identificar las instituciones del proyecto y rastrear sus coordenadas geográficas. Se elaboró un mapa georreferenciado utilizando el lenguaje de programación R y, a partir de la ubicación geográfica de los desarrolladores de vacunas, se analizó la distribución subcontinental de los ensayos clínicos y la naturaleza de las vacunas probadas. A nivel regional, los países del Sur Sureste Asiático llevaron a cabo proporcionalmente más ensayos clínicos que cualquier otra región, aunque esto se realizó con tecnologías consolidadas. Se registraron pocos ensayos en la etapa de implementación en América Latina y África. Los hallazgos confirman los estudios previos sobre la concentración regional en el desarrollo tecnológico. Sin embargo, permiten un aporte al demostrar estos fenómenos para vacunas contra el COVID-19 en subcontinentes y tecnologías específicas a nivel nacional. Los datos revelan los subcontinentes que realizan pocos ensayos clínicos para el COVID-19 y que no parecen estar bien preparados para futuros brotes de enfermedades, en caso de que se conviertan en epidemias o incluso pandemias, requiriendo el desarrollo o la producción de vacunas nacionales. Se considera también el caso de Brasil, que no completó el ciclo completo de desarrollo de la vacuna contra el COVID-19 en el periodo señalado; pero, con políticas favorables, tiene el potencial de involucrarse aún más en la tecnología de la vacuna del COVID-19.

A review on risk assessment of formulation development and technology transfer of COVID-19 vaccines / Una revisión sobre la evaluación de riesgos del desarrollo de formulaciones y la transferencia de tecnología de las vacunas COVID-19

Background: COVID-19 pandemic situation made the pharmaceutical companies develop the vaccine with different formulations in a short period. Objectives: The main objective of the review is to focus on different types of vaccine formulations available globally and the importance of technology transfer in vaccine development associated with potential risks. Results: Research on vaccine development led to various types of vaccines, such as Inactivated vaccines, Live Attenuated vaccines, Ribonucleic acid (RNA) and Deoxyribonucleic acid (DNA) vaccines, viral vector vaccines, and Protein Subunit Vaccines for COVID-19. But the process of vaccine development and technology transfer is lined with various risks and challenges. Through risk assessment, we found some major potential risks involved in product development; this leads to a smoother and more efficient method to develop safe vaccines available for public health. Conclusions: This review will explain the significance of technology collaboration for the faster development of various formulations of vaccines globally

Antecedentes: La situación de pandemia de COVID-19 hizo que las empresas farmacéuticas desarrollaran la vacuna con diferentes formulaciones en un corto período. Objetivos: El objetivo principal de la revisión es centrarse en los diferentes tipos de formulaciones de vacunas disponibles a nivel mundial y la importancia de la transferencia de tecnología en el desarrollo de vacunas asociado con los riesgos potenciales. Resultados: La investigación sobre el desarrollo de vacunas condujo al desarrollo de varios tipos de vacunas, como vacunas inactivadas, vacunas vivas atenuadas, vacunas de ácido ribonucleico (ARN) y ácido desoxirribonucleico (ADN), vacunas de vectores virales y vacunas de subunidades de proteínas para COVID-19. Pero el proceso de desarrollo de vacunas y transferencia de tecnología está lleno de varios riesgos y desafíos. A través de la evaluación de riesgos, encontramos algunos riesgos potenciales importantes involucrados en el desarrollo de productos, lo que conduce a un método más fluido y eficiente para desarrollar vacunas seguras disponibles para la salud pública. Conclusiones: Esta revisión dará una idea de la importancia de la colaboración tecnológica para el desarrollo más rápido de varias formulaciones de vacunas a nivel mundial

Strategies for syphilis vaccine development

Research to identify a syphilis vaccine began shortly after the isolation of the first Treponema pallidum subspecies pallidum (T. pallidum) strain in 1912 by Nichols and Hough and the identification of several possible animal models for the infection, with the rabbit being the best one. During the century following T. pallidum isolation, none of the numerous immunization/challenge experiments performed with preparations ranging from whole-inactivated T. pallidum cells to recombinant proteins yielded an effective vaccine, and the search for a vaccine languished. Recently, however, scientific communities have experienced a resurgence in interest in developing a syphilis vaccine due to 1. the awareness that syphilis constitutes a tremendous burden for maternal health, particularly in low- and middle-income nations; 2. the improved understanding of the immunological processes leading to pathogen clearance during natural infection and of the mechanisms this pathogen developed to persist in the host; 3. the availability of a near-complete list of T. pallidum genes encoding putative surface-exposed antigens, which represent the most likely vaccine candidates; and, last but not least, 4. the effort made to expand the knowledge on the genetic and antigenic diversity of these vaccine candidates in strains circulating worldwide. Thus far, the most recent vaccine designs based on a subset of the pathogen's surface-exposed antigens have provided immunized rabbits with a significant but incomplete protection upon infectious challenge. Nonetheless, the outcomes of these experiments help investigators refine strategies to achieve a formulation with the highest chances of moving from preclinical experimental settings to clinical trials. This editorial focuses on a subset of the strategies currently believed to be essential for vaccine development, namely, the improvement of our still limited understanding of the genomic diversity in T. pallidum strains from diverse geographical locations through the collection and isolation of modern syphilis strains and the identification of protective epitopes in potential vaccine targets by evaluating the ability of monoclonal antibodies to bind the target antigen and facilitate pathogen clearance. The use of genetic engineering of the syphilis spirochete to identify target surface proteins with an essential or near-essential role in T. pallidum biology to target in immunization/challenge experiments is also discussed.

Clustered Regularly Interspaced Short Palindromic Repeats/ CRISPR associated protein 9-mediated editing of Schistosoma mansoni genes: Identifying genes for immunologically potent drug and vaccine development

ABSTRACT Schistosomiasis is a neglected acute and chronic tropical disease caused by intestinal (Schistosoma mansoni and Schistosoma japonicum) and urogenital (Schistosoma haematobium) helminth parasites (blood flukes or digenetic trematodes). It afflicts over 250 million people worldwide, the majority of whom reside in impoverished tropical and subtropical regions in sub-Saharan Africa. Schistosomiasis is the second most common devastating parasitic disease in the world after malaria and causes over 200,000 deaths annually. Currently, there is no effective and approved vaccine available for human use, and treatment strongly relies on praziquantel drug therapy, which is ineffective in killing immature larval schistosomula stages and eggs already lodged in the tissues. The Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein 9 (CRISPR/Cas9)-mediated gene editing tool is used to deactivate a gene of interest to scrutinize its role in health and disease, and to identify genes for vaccine and drug targeting. The present review aims to summarize the major findings from the current literature reporting the usage of CRISPR/Cas9-mediated gene editing to inactivate genes in S. mansoni (acetylcholinesterase (AChE), T2 ribonuclease omega-1 (ω1), sulfotransferase oxamniquine resistance protein (SULT-OR), and α-N-acetylgalactosaminidase (SmNAGAL)), and freshwater gastropod snails, Biomphalaria glabrata (allograft inflammatory factor (BgAIF)), an obligatory component of the life cycle of S. mansoni, to identify their roles in the pathogenesis of schistosomiasis, and to highlight the importance of such studies in identifying and developing drugs and vaccines with high therapeutic efficacy.

COVID-19 vaccine candidates and vaccine development platforms available worldwide / 药物分析学报

The pandemic caused by the worldwide spread of the coronavirus,which first appeared in 2019,has been named coronavirus disease 19 (COVID-19).More than 4.5 million deaths have been recorded due to the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),according to the World Health Organization.COVID-19 Dashboard in September 2021.Apart from the wildtype,other variations have been successfully transmitted early in the outbreak although they were not discovered until March 2020.Modifications in the SARS-CoV-2 genetic material,such as mutation and recombi-nation,have the ability to modify the viral life span,along with transitivity,cellular tropism,and symptom severity.Several processes are involved in introducing novel vaccines to the population,including vaccine manufacturing,preclinical studies,Food and Drug Administration permission or cer-tification,processing,and marketing.COVID-19 vaccine candidates have been developed by a number of public and private groups employing a variety of strategies,such as RNA,DNA,protein,and viral vectored vaccines.This comprehensive review,which included the most subsequent evidence on unique features of SARS-CoV-2 and the associated morbidity and mortality,was carried out using a systematic search of recent online databases in order to generate useful knowledge about the COVID-19 updated versions and their consequences on the disease symptoms and vaccine development.

Active researches on prevention and treatment of COVID-19 by Chinese scholars with signifícant results / 中国药理学通报

At present, novel Coronavirus is spreading wordwide, with rapid speed, strong transinissibility and many spreading channels. On January 31, 2020, WHO declared the pneumonia (COVID-19) outbreak caused by novel Coronavirus to be "an public health emergency of international concern". As of May 31, 2020, Beijing time, the cumulative number of confirmed COVID-19 cases worldwide had exceeded 6.21 million, and the cumulative number of deaths had exceeded 370 000. The outbreak of COVID-19 has prompted Chinese medical and health prevention researchers to carry out a large number of studies on COVID-19, and the important achievements have been published in many medical journals at home and abroad. Through CNKI, this study analyzed and summarized COVID-19 related articles published by Chinese scholars in domestic medical journals from January to April 2020. It was found that COVID-19 related articles were published in a wide range of journals and research institutions, including hospitals, universities, research institutes and pharmaceutical companies. The research content is comprehensive, including pathogenesis, virus antibody detection, COVID-19 diagnosis, epidemic prevention and control strategies, vaccine development and treatment drug development, etc. The treatment of COVID-19 is multipath,including anti-virus, improving the body' s immunity. Western medicine treatment, TCM conditioning and integrated treatment of traditional Chinese and Western medicine. These research findings and diagnosis and treatment experience provide important references for the prevention and treatment of COVID-19 around the world.

Characteristics of African swine fever virus and difficulties in vaccine development / 生物工程学报

African swine fever (ASF) is a devastating disease of pigs caused by African swine fever virus (ASFV), which is considered to be the No. 1 killer to the global pig industry. Highly virulent strains are usually responsible for the peracute and acute forms that provoke high mortality rates that may reach 100%. Since ASF was first introduced in August 2018 into China, 137 outbreaks in domestic and wild pigs had been reported from 32 provinces by June 06, 2019, causing severe socioeconomic consequences. Efforts to develop an ASFV vaccine began in the 1960s, but all failed, the major reason is the lack of in-depth research on the biological characteristics of ASFV. It will be a great challenge for China to control the spread of current ASF, develop safe and effective vaccines. In this review, we outline the biological characteristics of ASFV, including its morphology and basic structure, transmission routes, pathogenicity, genome and proteins, entry mechanism, immune escape, and analyzed the difficulties in vaccine development. We hope to provide basic information for the control of current ASF and understanding of etiology in China.

Dengue, zika, chikungunya y el desarrollo de vacunas / Dengue, zika, chikungunya and the development of vaccines

Dengue (DENV), zika (ZIKV) y chikungunya (CHIKV), tres arbovirosis transmitidas por mosquitos Aedes, se han propagado en las últimas décadas en zonas tropicales y subtropicales húmedas. El dengue es epidémico en áreas subtropicales de la Argentina. Después de la infección por DENV hay inmunidad duradera contra el serotipo infectante, pero aumenta el riesgo de enfermedad grave por los otros tres. La vacuna recombinante tetravalente, Dengvaxia® previene el dengue grave y la hospitalización en sujetos seropositivos. En 2017 se aprobó Dengvaxia en Argentina, para edades de 9 a 45 años, sin incluirla en el calendario nacional de vacunación. Otras dos vacunas se hallan en evaluación Fase III: la desarrollada por NIAID/ Instituto Butantan y la vacuna Takeda. ZIKV, virus asociado a microcefalia en recién nacidos en Brasil, circula desde 2016 en Argentina. Aún no existe vacuna de actividad comprobada contra ZIKV ni tratamiento eficaz. No se registró circulación activa de CHIKV en Argentina en 2017. Los brotes de fiebre CHIKV tienen una complicación: el desarrollo de reumatismo crónico post-enfermedad. No existen vacunas aprobadas para humanos ni terapias antivirales efectivas. La gravedad de estas virosis contribuyó a un rápido progreso en el conocimiento de los procesos de infección y de la respuesta inmune. Pero sus vectores, Aedes aegypti y A. albopictus, continúan expandiéndose, lo que indica que la vacuna será el medio más efectivo para el control. Se resume aquí información sobre estas arbovirosis en Argentina y Brasil, y se describen avances en el desarrollo y la evaluación de vacunas.

Dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjects. In 2017, Dengvaxia was approved in Argentina, for ages 9 to 45, but is not included in the national vaccination calendar. Two other vaccines are in Phase III evaluation: one developed by NIAID / Instituto Butantan and the other by Takeda.ZIKV, a virus associated with microcephaly in newborns in Brazil, circulates since 2016 in Argentina. There is still not effective treatment nor vaccine with proven activity against ZIKV. There has been no active circulation of CHIKV in Argentina in 2017. Outbreaks of CHIKV fever have a complication: the development of chronic post-disease rheumatism. There are not approved vaccines for humans nor effective antiviral therapies. The seriousness of these virosis has contributed to a rapid progress in the knowledge of the infection processes and the immune response. For now, Aedes aegypti and A. albopictus vectors continue to expand, suggesting that the vaccine will be the most effective means of controlling these viruses. Here we summarize information about these arbovirosis in Argentina and Brazil and describe advances in the development and evaluation of vaccines.

Research progress of AIDS treatment / 中国人兽共患病学报

AIDS antiviral therapy (ART) has achieved great success.Originaly,AIDS had been regarded as a fatal disease,but it has become a kind of infectious disease that could be cured and administrated.Global HIV / AIDS cases were still up to about 38 million,but more than half have been effectively treated.In addition to drug treatment,at present,some new technologies and new methods,such as genome editing,have also been involved in the treatment of AIDS,and in the humanized animal experiment has shown very good results.There is no doubt that AIDS will eventually be stopped its epidemic.However,with the continuous development of AIDS antiviral treatment,the most fundamental problem is that HIV latent library has become increasingly prominent one,whether molecular therapy and hybrid cure have being developed for AIDS treatment,there are still such problem existence.Great efforts shoud be made to continuously search for new markers of latent viral cells and to reduce the latent pool.In addition,despite the prevention and treatment of AIDS has made great achievements,but the world still produces nearly 6000 cases of HIV/AIDS every day.Therefore,the development of safe and effective vaccine,whether in the field of prevention,or in clinical treatment,has its positive significance.

Platform for Plasmodium vivax vaccine discovery and development

Plasmodium vivax is the most prevalent malaria parasite on the American continent. It generates a global burden of 80-100 million cases annually and represents a tremendous public health problem, particularly in the American and Asian continents. A malaria vaccine would be considered the most cost-effective measure against this vector-borne disease and it would contribute to a reduction in malaria cases and to eventual eradication. Although significant progress has been achieved in the search for Plasmodium falciparum antigens that could be used in a vaccine, limited progress has been made in the search for P. vivax components that might be eligible for vaccine development. This is primarily due to the lack of in vitro cultures to serve as an antigen source and to inadequate funding. While the most advanced P. falciparum vaccine candidate is currently being tested in Phase III trials in Africa, the most advanced P. vivax candidates have only advanced to Phase I trials. Herein, we describe the overall strategy and progress in P. vivax vaccine research, from antigen discovery to preclinical and clinical development and we discuss the regional potential of Latin America to develop a comprehensive platform for vaccine development.

The utility of rhesus monkey (Macaca mulatta) and other non-human primate models for preclinical testing of Leishmania candidate vaccines

Leishmaniasis causes significant morbidity and mortality, constituting an important global health problem for which there are few effective drugs. Given the urgent need to identify a safe and effective Leishmania vaccine to help prevent the two million new cases of human leishmaniasis worldwide each year, all reasonable efforts to achieve this goal should be made. This includes the use of animal models that are as close to leishmanial infection in humans as is practical and feasible. Old world monkey species (macaques, baboons, mandrills etc.) have the closest evolutionary relatedness to humans among the approachable animal models. The Asian rhesus macaques (Macaca mulatta) are quite susceptible to leishmanial infection, develop a human-like disease, exhibit antibodies to Leishmania and parasite-specific T-cell mediated immune responses both in vivo and in vitro, and can be protected effectively by vaccination. Results from macaque vaccine studies could also prove useful in guiding the design of human vaccine trials. This review summarizes our current knowledge on this topic and proposes potential approaches that may result in the more effective use of the macaque model to maximize its potential to help the development of an effective vaccine for human leishmaniasis.