The development of adjuvants will represent a major challenge for this century. Indeed the need for safer vaccines leads to the development of a new generation of antigens like synthetic peptide, recombinant proteins or even vectored DNA. However, this is to the detriment of their immunogenicity. The addition of adjuvant is becomes necessary to enhance immune responses and improve vaccine potency. However, adjuvants can be responsible for the apparition of secondary reactions and they must be adapted according to various criteria such as the route of immunization, the type of the immune response, the duration of immunity, or the quality of the antigen, in order to get the best balance between efficacy and safety.

Background Plasmodium falciparum Apical Membrane Antigen 1 (PfAMA1) is a candidate vaccine antigen expressed by merozoites and sporozoites. It plays a key role in red blood cell and hepatocyte invasion that can be blocked by antibodies.Methodology/Principal FindingsWe assessed the safety and immunogenicity of recombinant PfAMA1 in a dose-escalating, phase Ia trial. PfAMA1 FVO strain, produced in Pichia pastoris, was reconstituted at 10 µg and 50 µg doses with three different adjuvants, Alhydrogel™, Montanide ISA720 and AS02 Adjuvant System. Six randomised groups of healthy male volunteers, 8–10 volunteers each, were scheduled to receive three immunisations at 4-week intervals. Safety and immunogenicity data were collected over one year. Transient pain was the predominant injection site reaction (80–100%). Induration occurred in the Montanide 50 µg group, resulting in a sterile abscess in two volunteers. Systemic adverse events occurred mainly in the AS02 groups lasting for 1–2 days. Erythema was observed in 22% of Montanide and 59% of AS02 group volunteers. After the second dose, six volunteers in the AS02 group and one in the Montanide group who reported grade 3 erythema (>50 mm) were withdrawn as they met the stopping criteria. All adverse events resolved. There were no vaccine-related serious adverse events. Humoral responses were highest in the AS02 groups. Antibodies showed activity in an in vitro growth inhibition assay up to 80%. Upon stimulation with the vaccine, peripheral mononuclear cells from all groups proliferated and secreted IFNγ and IL-5 cytokines.Conclusions/SignificanceAll formulations showed distinct reactogenicity profiles. All formulations with PfAMA1 were immunogenic and induced functional antibodies.Trial RegistrationClinicaltrials.gov NCT00730782

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Two inactivated antigens (Newcastle and Pasteurella Multocida) were formulated with different adjuvants and tested in two separate experiments in poultry. Oil formulations constituting water in oil (W/O) or water in oil in water (W/O/W) emulsions were assessed for antibody response, protection, local reactions, and vaccine physicochemical parameters. Robust, efficacious, and safe formulations were obtained with W/O formulations whereas W/O/W was especially safe with maintained efficacy. Results show that it is possible to improve traditional Tween Span formulations for safety and efficacy parameters by using Montanide ISA 70 for W/O formulations and Montanide ISA 206 for W/O/W when safety is the priority.