An experimental malaria vaccine, PfSPZ (Sanaria), has demonstrated promising results in protecting women anticipating pregnancy from Plasmodium falciparum infection, according to recent research published in The Lancet Infectious Diseases. The phase 1 and 2 trials, MLSPZV3 and MLSPZV4, conducted in Mali, assessed the safety and efficacy of the radiation-attenuated, non-replicating, whole-organism vaccine.
Trial Design and Results
The phase 1 MLSPZV3 trial enrolled adults aged 18 to 35 years, while the phase 2 MLSPZV4 trial focused on non-pregnant women aged 18 to 38 years who anticipated becoming pregnant within a year. Participants were randomized to receive either 3 doses of the PfSPZ vaccine (9 × 10^5 or 1.8 × 10^6) or a saline placebo, administered on a 4-week schedule (weeks 0, 1, and 4). All participants received artemether-lumefantrine before dose 3.
In the phase 2 MLSPZV4 trial, both doses of the PfSPZ vaccine showed significant efficacy against parasitemia at years 1 (9 × 10^5 dose: 41% [15 to 59], p = .0069; and 1.8 × 10^6 dose: 54% [34 to 69], p < .0001) and 2 (9 × 10^5 dose: 61% [36 to 77], p = .0011; and 1.8 × 10^6 dose: 45% [13 to 65], p = .029). Efficacy was also observed against clinical malaria for both doses at years 1 (9 × 10^5 dose: 47% [20 to 65], p = .0045; and 1.8 × 10^6 dose: 48% [22 to 65], p = .0013) and 2 (9 × 10^5 dose: 56% [22 to 75], p = .0081; and 1.8 × 10^6 dose: 40% [2 to 64], p = .069).
Impact on Pregnant Women
Notably, vaccine efficacy against post-conception P. falciparum parasitemia during first pregnancies that arose during the 2-year follow-up was approximately 57% (14 to 78; p = .017) in the 9 × 10^5 group compared with 49% (3 to 73; p = .042) in the 1.8 × 10^6 group. Among the 55 women who were pregnant within 24 weeks after receiving their third dose, vaccine efficacy was approximately 65% (23 to 84; p = .0088) with the 9 × 10^5 group and 86% (64 to 94; p < .0001) for the 1.8 × 10^6 group.
Safety Profile
The vaccine demonstrated a favorable safety profile. First trimester miscarriages were the most commonly reported serious adverse event, but occurred at a similar rate across study groups. The most related adverse events reported in MLSPZV3 and MLSPZV4 were mild, and the frequency of adverse events in the PfSPZ vaccine groups did not differ from that in the placebo group.
Implications for Malaria Prevention
These findings suggest that preconception immunization with the PfSPZ vaccine could be a valuable strategy in reducing malaria-related mortality in pregnant women. "Preconception immunization is a new strategy to reduce mortality for women with malaria in pregnancy. Existing measures are not protecting women from malaria in pregnancy. A safe and effective vaccine is urgently needed, and our results indicate PfSPZ Vaccine might be a suitable candidate," the researchers stated.
