An effective malaria vaccine is needed to address the public health tragedy resulting from the high levels of morbidity and mortality caused by Plasmodium parasites. The first protective immune mechanism identified in the irradiated sporozoite vaccine, the "gold standard" for malaria preerythrocytic vaccines, was sporozoiteneutralizing antibody specific for the repeat region of the surface circumsporozoite ( There is a critical need for an effective malaria vaccine, as standard public health measures have been eroded by drug resistance of the parasite and insecticide resistance of the mosquito vector. Moreover, traditional control measures have failed to prevent Plasmodium infections in 300 to 600 million people worldwide, resulting in over 1 million deaths each year (55). Vaccines remain the most cost-effective means for control of infectious diseases. Over the past 30 years, an effective malaria vaccine, based on attenuated sporozoites delivered by the bites of irradiated infected mosquitoes, has been shown to elicit sterile immunity in experimental animal models and human volunteers (11,25,27,45). However, large-scale production of an attenuated parasite vaccine faces significant practical limitations and logistical and regulatory hurdles that must be overcome. Sporozoites cannot be grown in culture and must be dissected from the salivary glands of infected mosquitoes that have fed on blood-stage parasites cultivated in human red blood cells. Additional challenges for attenuated sporozoite vaccines relate to cost, scale-up production, sterility, cold-chain storage, and route of immunization, which in humans has thus far been obtained only by exposure to the bites of irradiated infected mosquitoes. Nevertheless, the ability to elicit sterile protection following immunization with attenuated sporozoites provides a gold standard for development of subunit malaria vaccines that target the preerythrocytic stages of the parasite and effectively prevent initiation of the blood-stage infection responsible for clinical disease.In contrast to whole parasites, peptide vaccines can be readily synthesized from inexpensive, well-defined amino acid components and lyophilized for storage and transport. In recent years, peptide immunotherapeutics have been developed for human autoimmune diseases and allergies (21, 31), and peptide subunit vaccines for infectious diseases and treatment of cancer have been tested in clinical trials (3,24,32,33,52). The first phase I/II trial of a malaria synthetic peptide vaccine was carried out over 20 years ago to assess the efficacy of a peptide-protein conjugate vaccine, termed (NANP) 3 -TT, comprised of the immunodominant B-cell repeat epitope (NANP) 3 from the Plasmodium falciparum major surface circumsporozoite (CS) protein linked to tetanus toxoid (TT) as the protein carrier (26). Exposure of a small number of (NANP) 3 -TTimmunized volunteers to the bites of P. falciparum-infected mosquitoes demonstrated that the vaccine could elicit protective antibody responses against P. falciparum s...

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Leishmania guyanensis (L. g.)‐specific CD8+ T cells can be isolated from PBMC of subjects who have never been previously exposed to Leishmania. Cells that produce IFN‐γ in response to live L. g. are generated from naive CD45RA+ CD8+ T cells. The generation of L. g.‐specific CD8+ T cells requires the presence of whole L. g. or UV‐irradiated parasite but not the soluble antigens from L. g. promastigotes. The IFN‐γ‐producing T cells recognize a specific antigen, the Leishmania homologue of receptors of activated C kinases (LACK) and this antigen but not live L. g. can produce a strong IL‐10 response in CD45RA– CD4+ memory T cells from naive subjects. A single epitope (amino acid 156 – 173) is found to induce the IL‐10 synthesis. While the IFN‐γ‐producing cells are present among CD45RA+ CD8+ T cells that are CD62L– CDR7– and CLA–, the LACK‐reactive IL‐10‐producing cells are CD4+ T cells that are CD62L+ CCR7– and CLA–.

The Aotus monkey has been of great value in the pre-clinical study of malaria vaccine candidates. Several components of this primate's immune system have been studied and they display great similarity to their human counterparts. Cloning and sequencing studies have revealed extensive sequence polymorphisms in Aotus MHC-DRB with very high similarities to several human allelic lineages, grouping at least nine distinct MHC-DRB lineages. As the efficacy of peptide vaccines in this animal model may be strongly influenced by exon 2 MHC-DRB polymorphism, the availability of a reliable and rapid MHC-DRB typing method for three species of Aotus (Aotus nancymaae, Aotus vociferans and Aotus nigriceps) is necessary. Reference strand conformational analysis (RSCA) was used here for differentiating the distinctive Aotus MHC-DRB sequences' mobility using five fluorescently labelled references proved to be very useful for resolving closely related sequences, establishing the number of sequences transcribed in a particular monkey and their identity. The RSCA method's reliability in terms of identifying Aotus MHC-DRB sequences will facilitate evaluating individual responsiveness to vaccines and prompt studies associating susceptibility/resistance to infectious agents or auto-immune disease, for which Aotus monkeys may be considered to be an appropriate animal model.