A race against time for a vaccine?

#PfSPZ #Vaccination #Malaria #Immunogenicity  


In 2023, malaria affected more than 263 million people worldwide and caused nearly 600,000 deaths, according to the WHO. These alarming numbers have remained almost unchanged over the past decade, illustrating the stagnation of global efforts to eliminate this parasitic disease, despite massive investments. While the development of malaria vaccines marks undeniable scientific progress, their impact remains largely insufficient. For instance, the RTS,S/AS01 and R21/Matrix-M vaccines, although effective against severe forms in young children, have limitations: their protection against infection is low, it wanes quickly, requires multiple doses, and shows little efficacy in adults. These shortcomings significantly limit their potential in eradication strategies and highlight the need for more effective solutions.  

Against this backdrop, the WHO has recently raised its standards, calling for the development of vaccines capable of achieving at least 90% efficacy. The goal is clear: to target all age groups and strengthen mass vaccination campaigns towards elimination.  

It is within this demanding context that the PfSPZ Vaccine has attracted increasing attention. Developed from live, but irradiated, sporozoites to block replication, this vaccine uses a radically different approach from conventional recombinant protein-based vaccines. By including thousands of parasite antigens, PfSPZ could offer broader and longer-lasting protection, including against genetically diverse strains. Multiple clinical trials conducted in Africa and Europe have already shown its ability to induce sterile immunity, notably in naïve or semi-immune adults. The current challenge is to validate this efficacy in a simplified format, better suited to the operational constraints of endemic areas.  

Are two doses enough?  

The USSPZV7 trial was conducted among 31 adults who had never been exposed to malaria to evaluate a condensed vaccination schedule of the PfSPZ vaccine. This protocol included two doses administered one week apart (Day 1 and Day 8), followed by a booster on Day 29.  

Immunologically, the results show a significantly consistent response. Ninety-six percent of participants produced IgG and IgM antibodies targeting the circumsporozoite protein of Plasmodium falciparum, with IgG levels rising 99-fold and IgM levels increasing 1,110-fold just one week after the second dose.  

The vaccine also demonstrated a good safety profile. No serious adverse events were observed. Reported side effects were moderate, transient, and typically consisted of fatigue, subjective fever, or muscle aches, all resolving spontaneously in less than 24 hours. The frequency of these effects did not exceed that observed in the placebo group, supporting the safety of the vaccine under an intensified administration schedule. Most of these effects occurred after the second dose, a phenomenon already documented in other studies with closely spaced multi-dose protocols. However, no statistically significant correlation was established between these reactions and the intensity of the immune response. Reactogenicity therefore is not a reliable indicator of immunological efficacy.  

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Fast vaccination, effective vaccination?  

Malaria, a mosquito-borne parasitic disease, remains one of the leading causes of morbidity and mortality in many tropical regions. Despite current tools for prevention and treatment, progress in reducing incidence has stalled. The challenge is therefore twofold: developing vaccines that are more effective than those already available, while proposing administration strategies that are simple, rapid, and adapted to high-risk contexts.  

The USSPZV7 study aimed to assess the safety, tolerability, and immunogenicity of a condensed PfSPZ vaccine schedule, administered via direct intravenous injection according to an accelerated protocol. Results from the first two doses are encouraging. The vaccine is well tolerated, with no serious side effects, and induces a robust immune response in participants.  

The demonstrated safety profile and immunogenicity position the PfSPZ Vaccine as a promising option, especially for travelers or in the context of targeted elimination campaigns. Its suitability for short-term scheduling could facilitate operational deployment in settings with logistical constraints. The next step will be to test this protocol in larger trials, including more diverse populations—particularly children—and in endemic areas. If its clinical efficacy is confirmed, this accelerated immunization strategy could mark a decisive turning point in the global fight against malaria.   

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