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Background Plasmodium falciparum merozoite surface protein 3 is a malaria vaccine candidate that was identified, characterised, and developed based on a unique immuno-clinical approach. The vaccine construct was derived from regions fully conserved among various strains and containing B cell epitopes targeted by human antibodies (from malaria-immune adults) that are able to mediate a monocyte-dependent parasite killing effect. The corresponding long synthetic peptide was administered to 36 volunteers, with either alum or Montanide ISA720 as adjuvant.Methods and FindingsBoth formulations induced cellular and humoral immune responses. With alum, the responses lasted up to 12 mo. The vaccine-induced antibodies were predominantly of cytophilic classes, i.e., able to cooperate with effector cells. In vitro, the antibodies induced an inhibition of the P. falciparum erythrocytic growth in a monocyte-dependent manner, which was in most instances as high as or greater than that induced by natural antibodies from immune African adults. In vivo transfer of the volunteers' sera into P. falciparum–infected humanized SCID mice profoundly reduced or abrogated parasitaemia. These inhibitory effects were related to the antibody reactivity with the parasite native protein, which was seen in 60% of the volunteers, and remained in samples taken 12 mo postimmunisation.ConclusionThis is the first malaria vaccine clinical trial to clearly demonstrate antiparasitic activity by vaccine-induced antibodies by both in vitro and in vivo methods. The results, showing the induction of long-lasting antibodies directed to a fully conserved polypeptide, also challenge current concepts about malaria vaccines, such as unavoidable polymorphism, low antigenicity, and poor induction of immune memory.

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Background Tuberculosis remains one of the world's deadliest transmissible diseases despite the widespread use of BCG. MTBVAC is a new live tuberculosis vaccine based on a genetically attenuated phoP-/fadD26-deletion mutant of M. tuberculosis that expresses most antigens present in human isolates in contrast to BCG. Methods We conducted this randomized, double-blind, controlled phase I study at CHUV, Lausanne, Switzerland, to compare MTBVAC to BCG in healthy, PPD-negative adults. Primary outcome was safety in all vaccinated participants. Secondary outcome included whole blood cell mediated immune response to live MTBVAC and BCG as well as interferon-gamma release assay (IGRA) on peripheral blood mononuclear cells. Volunteers fulfilling the inclusion criteria were randomly allocated (on a 3:1 basis) in a dose-escalation manner to three cohorts. Each cohort included 9 subjects who were injected with MTBVAC 5x10 3 , 5x10 4 , or 5x10 5 colony forming units (CFU) in 0.1 mL and 3 subjects with BCG (single dose of 5x10 5 CFU in 0.1 mL). Each subject received a single intradermal injection in the non-dominant arm starting with the lowest MTBVAC dose. Findings Thirty-six volunteers were recruited. Vaccination with MTBVAC (5x10 3 , 5x10 4 , 5x10 5 CFU/0.1mL) was as safe as with BCG, and did not induce serious adverse events. All individuals were IGRA negative at the end of follow-up (D210). After whole blood stimulation with live MTBVAC or BCG, MTBVAC was immunogenic in a dosedependent manner. At the same dose level as BCG (5x10 5 CFU), although no