LAUSR

Following the RTS,S malaria vaccine, which showed only partial protection with short-term memory, there is strong support to develop second-generation malaria vaccines that yield higher efficacy with longer duration. The use of replicating viral vectors to deliver subunit vaccines is of great interest due to their capacity to induce efficient cellular immune responses and long-term memory. The measles vaccine virus offers an efficient and safe live viral vector that could easily be implemented in the field. Here, we produced recombinant measles viruses (rMV) expressing malaria “gold standard” circumsporozoïte antigen (CS) of Plasmodium berghei (Pb) and Plasmodium falciparum (Pf) to test proof of concept of this delivery strategy. Immunization with rMV expressing PbCS or PfCS induced high antibody responses in mice that did not decrease for at least 22 weeks post-prime, as well as rapid development of cellular immune responses. The observed long-term memory response is key for development of second-generation malaria vaccines. Sterile protection was achieved in 33% of immunized mice, as usually observed with the CS antigen, and all other immunized animals were clinically protected from severe and lethal Pb ANKA-induced cerebral malaria. Further rMV-vectored malaria vaccine candidates expressing additional pre-erythrocytic and blood-stage antigens in combination with rMV expressing PfCS may provide a path to development of next generation malaria vaccines with higher efficacy.Malaria: Recombinant measles virus malaria vaccineFollowing the limited success of the RTS,S recombinant malaria vaccine there is a pressing need for second generation malaria vaccines. Frédéric Tangy and colleagues at the Pasteur Institute, Paris, generate novel vaccines based on recombinant measles virus (rMV) expressing the major circumsporozoite antigen CS from either Plasmodium berghei (rMV-CSPb) or P. falciparum (rMV-CSPf). rMV is a strong vector candidate because of its widespread use, safety profile and efficacy. Mice permissive to rMV infection show rapid and durable (at least 22 weeks) CS antibody responses as well as activation of cell-mediated immunity and type 1 helper responses following vaccination with rMV-CSPb or rMV-CSPf. rMV-CSPb vaccination protects mice from lethal challenge with Pb sporozoites, and in a subset of mice leads to sterile immunity. The rMV vector offers the potential of incorporating further antigens from other Plasmodium infection stages and thereby enhancement of vaccine efficacy.