Progress with Plasmodium falciparum sporozoite (PfSPZ)-based malaria vaccines

Abstract

Sanaria Inc. has developed methods to manufacture, purify and cryopreserve aseptic Plasmodium falciparum (Pf) sporozoites (SPZ), and is using this platform technology to develop an injectable PfSPZ-based vaccine that provides high-grade, durable protection against infection with Pf malaria. Several candidate vaccines are being developed and tested, including PfSPZ Vaccine, in which the PfSPZ are attenuated by irradiation, PfSPZ-CVac, in which fully infectious PfSPZ are attenuated in vivo by concomitant administration of an anti-malarial drug, and PfSPZ-GA1, in which the PfSPZ are attenuated by gene knockout. Forty-three research groups in 15 countries, organized as the International PfSPZ Consortium (I-PfSPZ-C), are collaborating to advance this program by providing intellectual, clinical, and financial support. Fourteen clinical trials of these products have been completed in the USA, Europe and Africa, two are underway and at least 12 more are planned for 2015-2016 in the US (four trials), Germany (2 trials), Tanzania, Kenya, Mali, Burkina Faso, Ghana and Equatorial Guinea. Sanaria anticipates application to license a first generation product as early as late 2017, initially to protect adults, and a year later to protect all persons >6 months of age for at least six months. Improved vaccine candidates will be advanced as needed until the following requirements have been met: long-term protection against natural transmission, excellent safety and tolerability, and operational feasibility for population-wide administration. Here we describe the three most developed whole PfSPZ vaccine candidates, associated clinical trials, initial plans for licensure and deployment, and long-term objectives for a final product suitable for mass administration to achieve regional malaria elimination and eventual global eradication.

Keywords: Malaria vaccine; PfSPZ Challenge; PfSPZ Vaccine; PfSPZ-CVac; Plasmodium falciparum; Sporozoite.

Fig. 1

Direct venous inoculation (DVI) of PfSPZ [42]. Once the injection site is prepped with an antiseptic such as 70% isopropyl alcohol, needle insertion, loosening the tourniquet and vaccine injection take only about 10–15 s. Note the small size of the needle (25 gauge) and syringe (1 mL), and blood flashback confirming successful puncture of, in this case, the median cubital or cephalic vein. Veins in the back of the hand or side of the wrist may also be used. Photograph by B. Mordmüller.

Fig. 2

Clinical development plan for PfSPZ Vaccine. Current activities fall into Stage 2.