Manuel Elkin Patarroyo (born in 1946) received his M.D. degree from the Universidad Nacional de Colombia (National University of Colombia, School of Medicine) in 1971, where he is Full Professor for Molecular Pathology. He did postdoctoral studies at Rockefeller University in the United States with Professor Henry Kunkel and on Tumor Immunology at Karolinska Institute, Sweden, with Professor George Klein. In 1976, he founded the Instituto de Inmunología at the San Juan de Dios Hospital, fully devoted to the development of chemically synthesized vaccines, malaria being one of them, with the advice of Professors Bruce Merrifield and David Andreu (Rockefeller University), and Professor Richard Lerner (Scripps Research Institute). The first chemically synthesized vaccine against this scourging disease was published in Nature in 1987 followed by a large series of clinical and field trials in different parts of the world that allowed the conclusion of the feasibility of chemically synthesized vaccines. He has received numerous awards including the Award of the Third World Academy of Science (TWAS) in 1988, the Prince of Asturias Award in Science and Technology (Spain) in 1994, the Robert Koch Award (Germany) in 1994, the Medicin de l’année Award (France) in 1995, the Edinburgh Medal (England) in 1995, the National Science Award (Colombia) in 1986, 1984, 1982, and 1978, and 26 Honoris Causa Doctor degrees from different universities throughout the world. He is founder and current director of the Fundación Instituto de Inmunología de Colombia since 2001.

Manuel Alfonso Patarroyo (born in 1972) obtained both his M.D. and Dr.Sc. degrees from the National University of Colombia. He is currently Full Professor at the Universidad del Rosario School of Medicine in Bogotá, Colombia, and Adjunct Professor at the National University of Colombia School of Medicine. His research interests have been mainly focused on developing vaccines against Plasmodium vivax malaria and tuberculosis. He and his group have successfully tested a recombinant vaccine candidate against P. vivax in Aotus monkeys, becoming one of the leading groups in vaccine development against this scourging disease. Besides his work on infectious diseases, Professor Patarroyo has also been working on the molecular characterization of the immune system components of the Aotus monkey, an ideal experimental model for testing vaccines for humans. He is currently the head of the Molecular Biology Department at the Fundacion Instituto de Inmunologia de Colombia.

Seventeen million people die of transmittable diseases and 2/3 of the world’s population suffer them annually. Malaria, tuberculosis, AIDS, hepatitis, and reemerging and new diseases are a great threat to humankind. A logical and rational approach for vaccine development is thus desperately needed.

Protein chemistry provides the best tools for tackling these problems. The tremendous complexity of microbes, the different pathways they use for invading host cells, and the immune responses they induce can only be resolved by using the minimum subunit-based (chemically produced 20-mer peptides), multiantigenic (most proteins involved in invasion), multistage (different invasion mechanisms) vaccine development approach.

The most lethal form of malaria caused by Plasmodium falciparum (killing 3 million and affecting 500 million people worldwide annually) was used as target disease since many of its proteins, its invasion pathways, and its genome have been described recently. A New World primate (the Aotus monkey) is highly susceptibly to human malaria; its immune system molecules are 80–100% identical to those of its human counterpart, making it an excellent model for vaccine development.

Chemically synthesized 20-mer peptides, covering all the P. falciparum malaria proteins involved in red blood cell (RBC) invasion were synthesized by the classical t-Boc technology (based on synthetic SPf66 antimalarial vaccine information for identifying targets) and assayed in a highly sensitive, specific, and robust test for detecting receptor–ligand interactions between high-activity binding peptides (HABPs) and RBCs. HABPs were identified, some in which the molecule displays genetic variability (to be discarded due to their tremendous complexity) and elicits a strain-specific immune response and others that are conserved (no amino acid sequence variation).

Conserved HABPs were synthesized in a polymeric form by adding cysteines at their N- and C-terminal ends to be used for monkey immunization. They became nonimmunogenic (no antibodies were induced) nonprotection inducers (monkeys were not protected against P. falciparum malaria challenge with a highly infective strain) suggesting a code of immunological silence or nonresponsiveness for these conserved HABPs.

A large number of monkey trials involving a considerable number of Aotus monkeys were performed to break this code of immunological silence by replacing critical residues (determined by glycine peptide analogue scanning) to find that the following amino acid changes had to be made to render them antibody and protection inducing: F↔R; W↔Y; L↔H; I↔N; M↔K; P↔D; Q↔E; C↔T.

The three-dimensional (3D) structure of >100 of these native modified HABPs (determined by ¹H NMR) revealed that the following structural changes had all to be achieved to allow a better fit into the major histocompatibility complex class II (MHC II)−peptide−TCR complex to properly activate the immune system: α-helix shortening, modifying their β-turn, adopting segmental α-helix configuration, changing residue orientation, and increasing the distance of those residues fitting into the MHC II molecules from antigen-presenting cells. More than 100 such highly immunogenic, protection-inducing (against P. falciparum malaria) modified HABPs have been identified to date with this methodology, showing that it could lead to developing a highly effective subunit-based, multiantigenic, multistage synthetic vaccine against diseases scourging humankind, malaria being one of them.