Advancing Global Health through Development and Clinical Trials Partnerships: A Randomized, Placebo-Controlled, Double-Blind Assessment of Safety, Tolerability, and Immunogenicity of PfSPZ Vaccine for Malaria in Healthy Equatoguinean Men

Abstract

Abstract.Equatorial Guinea (EG) has implemented a successful malaria control program on Bioko Island. A highly effective vaccine would be an ideal complement to this effort and could lead to halting transmission and eliminating malaria. Sanaria® PfSPZ Vaccine (Plasmodium falciparum sporozoite Vaccine) is being developed for this purpose. To begin the process of establishing the efficacy of and implementing a PfSPZ Vaccine mass vaccination program in EG, we decided to conduct a series of clinical trials of PfSPZ Vaccine on Bioko Island. Because no clinical trial had ever been conducted in EG, we first successfully established the ethical, regulatory, quality, and clinical foundation for conducting trials. We now report the safety, tolerability, and immunogenicity results of the first clinical trial in the history of the country. Thirty adult males were randomized in the ratio 2:1 to receive three doses of 2.7 × 105 PfSPZ of PfSPZ Vaccine (N = 20) or normal saline placebo (N = 10) by direct venous inoculation at 8-week intervals. The vaccine was safe and well tolerated. Seventy percent, 65%, and 45% of vaccinees developed antibodies to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) by enzyme-linked immunosorbent assay, PfSPZ by automated immunofluorescence assay, and PfSPZ by inhibition of sporozoite invasion assay, respectively. Antibody responses were significantly lower than responses in U.S. adults who received the same dosage regimen, but not significantly different than responses in young adult Malians. Based on these results, a clinical trial enrolling 135 subjects aged 6 months to 65 years has been initiated in EG; it includes PfSPZ Vaccine and first assessment in Africa of PfSPZ-CVac. ClinicalTrials.gov identifier: NCT02418962.

Genetic polymorphism of Plasmodium falciparum circumsporozoite protein on Bioko Island, Equatorial Guinea and global comparative analysis

“…This result might be explained by the work of Guerra et al, which reported that the strong connection of human movement between Bioko and the mainland Equatorial Guinea (EG), determine a high vulnerability of Bioko to malaria importation; these studies reported that the odds of malaria infection in travellers who had been to mainland EG were more than three times the rest of the population, which con rmed that the majority malaria cases are actively imported by off-island travellers to mainland EG [41,42]. Furthermore, it is worth mention that the PfSPZ vaccine had been tested in Malabo and a series of clinical trials are undergoing, which might likely to affect the genetic background of the malaria parasites in this region [9]. According to the report [9], PfSPZ vaccine could induced the immune response to PfCSP, which might in uence the genetic diversity and natural selection of pfcsp in Malabo.…”

“…Furthermore, it is worth mention that the PfSPZ vaccine had been tested in Malabo and a series of clinical trials are undergoing, which might likely to affect the genetic background of the malaria parasites in this region [9]. According to the report [9], PfSPZ vaccine could induced the immune response to PfCSP, which might in uence the genetic diversity and natural selection of pfcsp in Malabo. The natural selection analysis revealed that Bioko pfcsp might under a selection effect although there is no statistical signi cance (p>0.1).…”

“…Besides of RTS,S/AS01, a live attenuated Plasmodium falciparum whole sporozoite (SPZ) vaccine is also regarded as a great potential malarial vaccine. Sanaria® PfSPZ Vaccine had conducted a clinical trial on Bioko Island where 70% vaccinees developed antibodies to P. falciparum circumsporozoite protein, which was the rst clinical trial conducted in Equatorial Guinea [9]. It is not hard to see that pfcsp is a very important gene for the host immune response to the P. falciparum invasion.…”

Mapping and enumerating houses and households to support malaria control interventions on Bioko Island

“…The household database is useful for recruiting households and individuals for ongoing and future studies. These include a malaria incidence study that is underway in a high prevalence area, as well as future vaccine trials on Bioko Island to assess the efficacy of a malaria vaccine candidate [21].…”

Advances in Vaccines

“…Development of malaria vaccine has been ongoing for more than 40 years. The fact that malaria is caused by parasites that makes the development of effective vaccine against malaria more difficult than the development of vaccines against bacteria and viruses [73][74][75][76][77][78].…”