Flaviviruses are emerging and re-emerging arthropod-borne pathogens responsible for significant mortality and morbidity worldwide. The genus comprises more than seventy small, positive-sense, single-stranded RNA viruses, which are responsible for a spectrum of human and animal diseases ranging in symptoms from mild, influenza-like infection to fatal encephalitis and haemorrhagic fever. Despite genomic and structural similarities across the genus, infections by different flaviviruses result in disparate clinical presentations. This review focusses on two haemorrhagic flaviviruses, dengue virus and yellow fever virus, and two neurotropic flaviviruses, Japanese encephalitis virus and Zika virus. We review current knowledge on host-pathogen interactions, virus entry strategies and tropism.

Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. WHO has classified the disease as emerging and uncontrolled and estimates that the infection results in two million new cases a year. There are 12 million people currently infected worldwide, and leishmaniasis threatens 350 million people in 88 countries. Current treatment is based on chemotherapy, which relies on a handful of drugs with serious limitations such as high cost, toxicity, difficult route of administration and lack of efficacy in endemic areas. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunization with defined subunit vaccines or live-attenuated strains of Leishmania. However, to date, no such vaccine is available despite substantial efforts by many laboratories. The major impediment in vaccine design is the translation of data from animal models to human disease, and the transition from the laboratory to the field. Furthermore, a thorough understanding of protective immune responses and generation and maintenance of the immunological memory, the most important and least-studied aspect of antiparasitic vaccine development, during Leishmania infection is needed. This review focuses on recent findings in antileishmania vaccine field and highlights current difficulties facing vaccine development and implementation.

Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. WHO estimates that the disease results in 2 million new cases a year, threatens 350 million people in 88 countries and that there are 12 million people currently infected worldwide. Current treatment is based on chemotherapy, which relies on a handful of drugs with serious limitations such as high cost, toxicity, difficult route of administration and lack of efficacy in endemic areas. Pentavalent antimonials have been the mainstay of antileishmanial therapy for over 70 years with second line drugs, Amphotericin B and Pentamidine, used in case of antimonial failure. Since the introduction of miltefosine at the beginning of this century, no new antileishmanial compounds have been approved for human treatment. Leishmaniasis is considered one of a few parasitic diseases likely to be controllable by vaccination. However, to date no such vaccine is available despite substantial efforts by many laboratories. The development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. This review outlines the current status of vaccine development and looks at the currently available chemotherapy as well as examples of drugs in development and different approaches to antileishmanial drug discovery and identification of novel antiparasitic compounds.

Preexisting T-cell immunity directed at conserved viral regions promotes enhanced recovery from influenza virus infections, with there being some evidence of cross-protection directed at variable peptides. Strikingly, many of the immunogenic peptides derived from the current pandemic A(H1N1)-2009 influenza virus are representative of the catastrophic 1918 “Spanish flu” rather than more recent “seasonal” strains. We present immunological and structural analyses of cross-reactive CD8 ⁺ T-cell–mediated immunity directed at a variable (although highly cross-reactive) immunodominant NP _418–426 peptide that binds to a large B7 family (HLA-B*3501/03/0702) found throughout human populations. Memory CD8 ⁺ T-cell specificity was probed for 12 different NP ₄₁₈ mutants that emerged over the 9 decades between the 1918 and 2009 pandemics. Although there is evidence of substantial cross-reactivity among seasonal NP ₄₁₈ mutants, current memory T-cell profiles show no preexisting immunity to the 2009-NP ₄₁₈ variant or the 1918-NP ₄₁₈ variant. Natural infection with the A(H1N1)-2009 virus, however, elicits CD8 ⁺ T cells specific for the 2009-NP ₄₁₈ and 1918-NP ₄₁₈ epitopes. This analysis points to the potential importance of cross-reactive T-cell populations that cover the possible spectrum of T-cell variants and suggests that the identification of key residues/motifs that elicit cross-reactive T-cell sets could facilitate the evolution of immunization protocols that provide a measure of protection against unpredicted pandemic influenza viruses. Thus, it is worth exploring the potential of vaccines that incorporate peptide variants with a proven potential for broader immunogenicity, especially to those that are not recognized by the current memory T-cell pool generated by exposure to influenza variants that cause successive seasonal epidemics.

Leishmaniaare protozoan parasites spread by a sandfly insect vector and causing a spectrum of diseases collectively known as leishmaniasis. The disease is a significant health problem in many parts of the world resulting in an estimated 12 million new cases each year. Current treatment is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective due to the emergence of drug resistance. Leishmaniasis is considered one of a few parasitic diseases likely to be controllable by vaccination. The relatively uncomplicated leishmanial life cycle and the fact that recovery from infection renders the host resistant to subsequent infection indicate that a successful vaccine is feasible. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunisation with protein or DNA vaccines. However, to date no such vaccine is available despite substantial efforts by many laboratories. Advances in our understanding ofLeishmaniapathogenesis and generation of host protective immunity, together with the completedLeishmaniagenome sequence open new avenues for vaccine research. The major remaining challenges are the translation of data from animal models to human disease and the transition from the laboratory to the field. This review focuses on advances in anti-leishmania vaccine development over the recent years and examines current problems hampering vaccine development and implementation.