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Protective efficacy and safety of radiation-attenuated and chemo-attenuated Plasmodium Falciparum sporozoite vaccines against controlled and natural malaria infection: a systematic review and meta-analysis of randomized controlled trials

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Abstract

Background and Objective

Despite the significant burden of Plasmodium falciparum (Pf) malaria and the licensure of two vaccines for use in infants and young children that are partially effective in preventing clinical malaria caused by Pf, a highly effective vaccine against Pf infection is still lacking. Live attenuated vaccines using Pf sporozoites as the immunogen (PfSPZ Vaccines) hold promise for addressing this gap. Here we review the safety and efficacy of two of the most promising PfSPZ approaches: PfSPZ Vaccine (radiation attenuated PfSPZ) and PfSPZ-CVac (chemo-attenuated PfSPZ).

Methods

We conducted a systematic review and meta-analysis by searching PubMed, EMBASE, SCOPUS, CENTRAL, and WOS until 22nd December 2021. We included randomized controlled trials (RCTs) of these two vaccine approaches that measured protection against parasitaemia following controlled human malaria infection (CHMI) in malaria-naive and malaria-exposed adults or following exposure to naturally transmitted Pf malaria in African adults and children (primary outcome) and that also measured the incidence of solicited and unsolicited adverse events as indicators of safety and tolerability after vaccination (secondary outcome).

We included randomized controlled trials (RCTs) that measured the detected parasitaemia after vaccination (primary outcome) and the incidence of various solicited and unsolicited adverse events (secondary outcome).

The quality of the included RCTs using the Cochrane ROB 1 tool and the quality of evidence using the GRADE system were evaluated. We pooled dichotomous data using the risk ratio (RR) for development of parasitemia in vaccinees relative to controls as a measure of vaccine efficacy (VE), including the corresponding confidence interval (CI). This study was registered with PROSPERO (CRD42022308057).

Results

We included 19 RCTs. Pooled RR favoured PfSPZ Vaccine (RR: 0.65 with 95% CI [0.53, 0.79], P = 0.0001) and PfSPZ-table (RR: 0.42 with 95% CI [0.27, 0.67], P = 0.0002) for preventing parasitaemia, relative to normal saline placebo. Pooled RR showed no difference between PfSPZ Vaccine and the control in the occurrence of any solicited adverse event (RR: 1.00 with 95% CI [0.82, 1.23], P = 0.98), any local solicited adverse events (RR: 0.73 with 95% CI [0.49, 1.08], P = 0.11), any systemic solicited adverse events (RR: 0.94 with 95% CI [0.75, 1.17], P = 0.58), and any unsolicited adverse event (RR: 0.93 with 95% CI [0.78, 1.10], P = 0.37).

Conclusion

PfSPZ and PfSPZ-CVacs showed comparable efficacy. Therefore, they can introduce a promising strategy for malaria prophylaxis, but more large-scale field trials are required to sustain efficacy and yield clinically applicable findings.

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Data availability

The data are available on request.

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Acknowledgements

Mohamed Abouzid is a participant in the STER Internationalization of Doctoral Schools Program of the NAWA Polish National Agency for Academic Exchange No. PPI/STE/2020/1/00014/DEC/02.

Funding

We received no funding for this study.

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Authors and Affiliations

  1. Faculty of Medicine, Tanta University, Tanta, Egypt

    Mohamed T. Abuelazm, Mohamed A. Elzeftawy, Helmy Badr, Mohamed Gamal, Mahmoud Aboulgheit & Sherief Abd-elsalam

  2. Faculty of Medicine, Benha University, Benha, Egypt

    Manar Ahmed Kamal

  3. Department of Cardiology, West Virginia University, Morgantown, WV, USA

    Basel Abdelazeem

  4. Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, Rokietnicka 3, 60-806, Poznan, Poland

    Mohamed Abouzid

  5. Doctoral School, Poznan University of Medical Sciences, Poznan, Poland

    Mohamed Abouzid

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  1. Mohamed T. Abuelazm
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Contributions

MTA conceived and designed the work. BA and MTA collected the data. MTA, MAE, MG, MAgheit, HB, and MAzid gave substantial contributions to data acquisition and interpretation for the work; MTA, MKA, and HB drafted the manuscript. BA, SA, MTA, MAE, and MAzid revised it critically for important intellectual content. All the authors gave the final approval of the version to be published and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Mohamed Abouzid.

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Abuelazm, M.T., Elzeftawy, M.A., Kamal, M.A. et al. Protective efficacy and safety of radiation-attenuated and chemo-attenuated Plasmodium Falciparum sporozoite vaccines against controlled and natural malaria infection: a systematic review and meta-analysis of randomized controlled trials. Infection (2024). https://doi.org/10.1007/s15010-024-02174-4

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