Whole-organism vaccines against P. falciparum and P. vivax malaria with enhanced efficacy and scope

Malaria is an infectious disease caused by Plasmodium parasites, among which P. falciparum (Pf) and P. vivax (Pv) exert the highest impact on human health. A licensed, highly effective vaccine for either Pf or Pv malaria remains unavailable. Whole-sporozoite (Wsp) vaccine candidates employing attenuated Pf parasites elicit high levels of protection against Pf malaria. However, it is generally accepted that their immunogenicity needs to be enhanced before they are applicable in the field. On the other hand, current limitations in the production of Pv sporozoites in the laboratory severely restrain the development of Wsp vaccines against Pv. Recently, rodent P. berghei (Pb) parasites, genetically modified to express antigens of their human-infective counterparts, have emerged as an alternative, “naturally attenuated” Wsp vaccination approach. PbWsp immunization has been recently validated in the clinic and was shown to be strongly immunogenic, although protective efficacy was lower than desired. PbWsp vaccination presents several advantages over Pf-based approaches, including its inherent safety and unmatched amenability to genetic modification. These features offer exceptional possibilities to enhance the efficacy and scope of action of PbWsp vaccines, comprising the ability to elicit stage- and species-transcending immunity. Having pioneered the concept of PbWsp vaccination and defined the current state-of-the-art of Plasmodium transgenesis, the MALVAX+ partners will harness the unique features of the PbWsp platform to generate, characterize and pre-clinically validate novel PbWsp vaccine candidates that elicit protective immune responses against antigens expressed by different stages of the Pf and Pv life cycles. We will further liaise with our Industrial sub-contractors to produce injectable formulations of the most promising vaccine candidates, delivering the next generation of Wsp vaccines against malaria, ready to enter the clinical development pathway.

La Caixa - Project Description

Enabling Technologies & Assays
Vaccines (Immune Correlates)

Jan 2021 — Dec 2023

$1.22M

Portugal

Towards a vaccine for Plasmodium vivax