Elastic liposome-mediated transdermal immunization enhanced the immunogenicity of P. falciparum surface antigen, MSP-119.

Transdermal immunization results in poor immunogenicity, which can be attributed to poor permeability of antigens through the skin. Therefore, elastic liposome, ultradeformable lipid vesicles, may overcome the challenges faced during transdermal immunization. This versatile carrier proves better vehicle for transcutaneous delivery of protein, peptide and nucleic acid antigens. The present results are suggestive of improved immunogenicity of carboxyl-terminal 19 kDa fragment of merozoite surface protein-1 (PfMSP-119) of Plasmodium falciparum when administered subcutaneously through elastic liposomes. The prepared elastic liposomes were characterized with respect to vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, stability and in vitro release. Humoral and cell-mediated immune (CMI) response elicited by topically applied PfMSP-119-loaded elastic liposomes, intramuscularly administered alum-adsorbed PfMSP-119 solution, and topically applied PfMSP-119-loaded conventional liposomes were compared and normalized with vehicle control. Results suggest greater transcutaneous immunization via elastic liposomes, and induced robust and perdurable IgG-specific antibody and cytophilic isotype responses. We report to have achieved sizeable CMI activating factor (IFNγ), a crucial player in conferring resistance to asexual blood stage malaria, responses with elastic liposomes when compared with other formulations. The fluorescence microscopy and histopathology results are suggestive of prominent skin permeation and biodistribution, and demonstrate efficient delivery of malaria antigen via elastic liposomes to immunocompetent Langerhans cells (LC) and lymphatics. In conclusion, elastic liposomal formulation provided greater entrapment efficiency, enhanced penetration and heightened and long-lasting immune response. Moreover, effective immunoadjuvant property of this carrier justifies its potential for improved vaccine delivery, and opens new avenues to explore further on the development of malaria vaccine.

Microneedle array design determines the induction of protective memory CD8+ T cell responses induced by a recombinant live malaria vaccine in mice.

BACKGROUND: Vaccine delivery into the skin has received renewed interest due to ease of access to the immune system and microvasculature, however the stratum corneum (SC), must be breached for successful vaccination. This has been achieved by removing the SC by abrasion or scarification or by delivering the vaccine intradermally (ID) with traditional needle-and-syringes or with long microneedle devices. Microneedle patch-based transdermal vaccine studies have predominantly focused on antibody induction by inactivated or subunit vaccines. Here, our principal aim is to determine if the design of a microneedle patch affects the CD8(+) T cell responses to a malaria antigen induced by a live vaccine. METHODOLOGY AND FINDINGS: Recombinant modified vaccinia virus Ankara (MVA) expressing a malaria antigen was percutaneously administered to mice using a range of silicon microneedle patches, termed ImmuPatch, that differed in microneedle height, density, patch area and total pore volume. We demonstrate that microneedle arrays that have small total pore volumes induce a significantly greater proportion of central memory T cells that vigorously expand to secondary immunization. Microneedle-mediated vaccine priming induced significantly greater T cell immunity post-boost and equivalent protection against malaria challenge compared to ID vaccination. Notably, unlike ID administration, ImmuPatch-mediated vaccination did not induce inflammatory responses at the site of immunization or in draining lymph nodes. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that the design of microneedle patches significantly influences the magnitude and memory of vaccine-induced CD8(+) T cell responses and can be optimised for the induction of desired immune responses. Furthermore, ImmuPatch-mediated delivery may be of benefit to reducing unwanted vaccine reactogenicity. In addition to the advantages of low cost and lack of pain, the development of optimised microneedle array designs for the induction of T cell responses by live vaccines aids the development of solutions to current obstacles of immunization programmes.

Assessment of safety of the major antimalarial drugs.

Antimalarial drugs remain the major intervention tool for the global malaria control efforts that save millions of lives. Nonetheless, emergence and spread of Plasmodium parasites resistant against chloroquine and other major antimalarial drugs has brought the urgency to develop a new generation of safe and effective drugs against malaria. In this article, the safety data for major antimalarial drugs is reviewed. Although an ample amount of clinical data regarding the safety and tolerability of several of these drugs in older children and adults is available, more critical safety and tolerability studies in pregnant women and young children is desirable. To offset the partial loss in efficacy due to drug resistance in malaria parasites acquired against specific drugs, treatment regimens often rely upon the combination of two or more drugs. However, combination therapy requires additional safety, toxicity and tolerability studies in all population groups where these drugs are administered. A uniform standard in assessing the safety and tolerability of antimalarial drugs will be useful in the formulation and implementation of malaria treatment policies that are based on the drug effectiveness, safety and tolerability.

Orally delivered malaria vaccines: not too hard to swallow.

Vaccines offer efficient and cost-effective protection against a wide range of infectious diseases. Unfortunately, no effective vaccine is yet available against malaria, and this infection remains one of the most important causes of human morbidity and mortality in the developing world. Over the past two decades a number of candidate proteins for inclusion in a subunit vaccine have been identified. Malariologists believe that an effective malaria vaccine will need to include multiple proteins that induce protective immune responses against different stages of the Plasmodium life cycle. The construction of such multivalent vaccines is beset by considerable logistical difficulties, not least of which is how to deliver them to a population living in endemic areas. Compared with other routes of vaccine administration, oral delivery has several advantages that make it an attractive strategy for vaccine development. This review summarises the progress towards an oral vaccine delivery system for malaria and discusses the feasibility of this approach.

Safety of a GM-CSF adjuvant-plasmid DNA malaria vaccine.

MuStDO 5 is a multivalent plasmid DNA vaccine for malaria comprised of five plasmid DNAs encoding five proteins from Plasmodium falciparum and one plasmid DNA encoding human GM-CSF. To evaluate the safety of MuStDO 5, a series of pre-clinical studies were conducted in mice and rabbits. In pharmacology studies in mice, GM-CSF could not be detected in the serum following either intramuscular or a combined intramuscular/intradermal administration of the vaccine, but was readily detected in the muscle following intramuscular administration. In a tissue distribution study in mice, MuStDO 5 plasmid DNA was detected by PCR initially in highly vascularized tissues, while at later time-points the plasmid DNA was detected primarily at the site(s) of injection. In GLP safety studies in mice and rabbits, repeated intramuscular/intradermal administration of the MuStDO 5 vaccine was found to be safe and well tolerated without any evidence of autoimmune pathology.

Controle da malária / Malaria control

No presente artigo é realizada uma discussão sobre o controle da malária, apontando seus novos rumos

El Complejo Mayor de Histocompatibilidad en Malaria: Implicaciones en el Desarrollo de Vacunas

El estudio de péptidos antigémicos candidatos al desarrollo de una vacuna contra la malaria por Plasmodium falciparum, ha mostrado la influencia del complejo mayor de histocompatibilidad humano en la respuesta inmune a determinados epítopes parásitarios. El estudio de la asociación entre el Antígeno Leucocitario Humano-B-53 (HLA) y la protección contra malaria severa ha permitido la caracterización de los péptidos presentados por esta molécula definiendo un epítope reconocido por los linfocitos T citotóxicos de los individuos protegidos. A pesar de que existen muchos hallazgos contradictorios, se sugiere la evaluación de este péptido como componente de una vacuna sintética. Otros hallazgos indican que algunas moléculas HLA clase II modifican la respuesta inmune humoral a antígenos parasitarios específicos mostrándose por ejemplo, una asociación positiva entre los portadores del alelo DQw2 y la respuesta de anticuerpos a la secuencia repetitiva (EENV)6 del antígeno Pf155/RESA o una asociación negativa entre los individuos homocigotos al antígeno HLA-DR4 y la respuesta inmune humoral al péptido sintético Spf66. Es importante estudiar los mecanismos por los cuales operan estas asociaciones para definir nuevos péptidos antigénicos potencialmente protectores, verificar el papel de otros genes cuyo locus está ubicado en la región HLA en el desarrollo de susceptibilidad o de resistencia a la infección y aumentar nuestro conocimiento sobre los procesos de selección natural de las moléculas HLA en las poblaciones considerando que el polimorfismo de estas moléculas ha surgido fundamentalmente por el encuentro con diferentes patógenos