Roberto Amador

Safety, tolerability and immunogenicity of new formulations of the Plasmodium falciparum malaria peptide vaccine SPf66 combined with the immunological adjuvant QS-21.

SPf66 is a synthetic malaria peptide vaccine, which has been widely tested in combination with aluminium hydroxide (alum) as the adjuvant. Since this formulation is weakly immunogenic, we sought to improve its immunogenicity by using the saponin adjuvant QS-21. SPf66/QS-21 vaccines were evaluated for safety, tolerability and immunogenicity in healthy adults. The vaccines were found to be safe in 87/89 (97.8%) volunteers studied. However, two individuals developed severe vaccine allergy following the third dose of 1/3 SPf66/QS-21 formulations tested. Vaccine formulations containing QS-21 induced a 45- to over 200-fold increase in anti-SPf66 IgG titres over the alum formulation after the second and third doses, respectively. Anti-SPf66 antibody from some subjects reacted against asexual blood stage parasites, as demonstrated by immunofluorescence and immunoblotting. Antibody responses generated by the QS-21 formulations were of longer duration compared to those evoked by the alum formulation. While SPf66/alum has been found to induce only CD4+ T cell response, the QS-21 formulations exhibited the potential to also elicit SPf66-specific CD8+ responses. These observations demonstrate that the use of QS-21 can substantially enhance the immunogenicity of peptide vaccines, such as SPf66.

The first field trials of the chemically synthesized malaria vaccine SPf66: safety, immunogenicity and protectivity

This paper reports the results of the first field study performed to assess the safety, immunogenicity and protectivity of the synthetic malaria vaccine SPf66 directed against the asexual blood stages of Plasmodium falciparum. Clinical and laboratory tests were performed on all volunteers prior to and after each immunization, demonstrating that no detectable alteration was induced by the immunization process. The vaccines were grouped as high, intermediate or low responders according to their antibody titres directed against the SPf66 molecule. Two of the 185 (1.08%) SPf66-vaccinated and nine of the 214 (4.20%) placebo-vaccinated volunteers developed P. falciparum malaria. The efficacy of the vaccine was calculated as 82.3% against P. falciparum and 60.6% against Plasmodium vivax.

Study of the safety and immunogenicity of the synthetic malaria SPf66 vaccine in children aged 1–14 years

Safety and immunogenicity tests of the SPf66 malaria vaccine have been carried out on a population of children, aged 1 to 14 years, in the town of Tumaco, Colombia. Adverse reactions measured after each vaccination were local and minimal, and observed in only a small percentage of the vaccinated children. One year later, no delayed reaction was evident. The majority of the child population developed high antibody titres against SPf66 and the degree of response did not vary with age. These induced antibodies recognize the native parasite proteins, in particular the molecules from which the amino acid sequence of this vaccine was deduced. These studies demonstrate that the SPf66 vaccine is safe and highly immunogenic for use in children greater than 1 year old.

Evaluation of SPf66 malaria vaccine during a 22-month follow-up field trial in the Pacific coast of Colombia.

A double-blind randomized placebo-controlled field trial with the SPf66 malaria vaccine was carried out in an endemic area consisting of 14 small villages with exclusive fluvial access, in a rain forest area along the Rosario River, Colombia. A total of 1257 subjects completed the full three dose vaccination schedule on days 0, 30 and 180 (643 vaccinated group/623 placebo group) and were followed-up by passive and active surveillance over a period of 22 months. One hundred and thirty-four Plasmodium falciparum malaria episodes were detected (53 in vaccinated group/81 in placebo group), yielding an attack rate of 5.47 cases/100 person years of follow-up (pyears) in the vaccine group and 8.44/100 pyears in the placebo group. The estimated vaccine protective efficacy was 35.2% (95% CI 8.4-54.2%, P = 0.01). This result supports earlier findings that the SPf66 malaria vaccine diminishes the risk of infection by P. falciparum in endemic areas of South America.

Genetic control of the immune response to a synthetic vaccine against Plasmodium falciparum

Summary Two independent vaccination trials using a hybrid synthetic poly pep‐tide containing epitopes from four proteins of Plasmodium falciparum were performed. In the first trial 63 and in the second 122 volunteers were vaccinated, using different immunization schedules. The analysis of the humoral response to the vaccine, measured by IgG antibody titres to the polypeptide showed a bimodal distribution in both cases suggesting genetic control of the immune response to this protein. There was a small group of low or non‐responders and a large group of good responders. HLA phenotyping of the two groups disclosed an association of the low responders to HLA‐DR4 antigens with chi‐square P value of 0.00039 when compared with the good responders group. These findings provide evidence for the genetic control of the immune response to the synthetic vaccine by the association of this response with particular alleles of the HLA class II antigens; such findings may lead to an explanation of the mechanism involved in disease susceptibility and need to be used in the design of a totally effective vaccine.

Arte y Ciencia-El arte de Pensar con arte

espanolLas obras de arte no son el todo en el arte. El arte es una forma de pensar, es pensamiento extremo, esta en la cotidianidad, esta en cualquiera de nosotros, puede ser extremo-extremo (el artista y la obra de arte). La educacion artistica es la guia en su construccion. La estetica es emocion, es pensamiento con sentimiento. EnglishWorks of art are not everything in art. Art is a way of thinking. It is, in fact, an extreme form of thinking which is present in everyday life, as well as in each one of us, and may be far-end (the artist and the work of art). And artistic education is the scheme through which its construction may be achieved. Aesthetics are emotion, a way of thinking through feeling. portuguesAs obras de arte nao sao tudo na arte. A arte e uma forma de pensar, e pensamento extremo, esta no quotidiano, esta em qualquer um de nos, pode ser extremo-extremo (o artista e a obra de arte). A educacao artistica e o guia na sua construcao. A estetica e emocao, e pensamento com sentimento.