Plasmodium falciparum merozoite surface protein 1 as asexual blood stage malaria vaccine candidate

ABSTRACT

Introduction

Malaria represents a public health challenge in tropical and subtropical regions, and currently deployed control strategies are likely insufficient to drive elimination of malaria. Development and improvement of malaria vaccines might be key to reduce disease burden. Vaccines targeting asexual blood stages of the parasite have shown limited efficacy when studied in human trials conducted over the past decades.

Areas covered

Vaccine candidates based on the merozoite surface protein 1 (MSP1) were initially envisioned as one of the most promising approaches to provide immune protection against asexual blood-stage malaria. Successful immunization studies in monkey involved the use of the full-length MSP1 (MSP1_FL) as vaccine construct. Vaccines using MSP1_FL for immunization have the potential benefit of including numerous conserved B-cell and T-cell epitopes. This could result in improved parasite strain-transcending, protective immunity in the field. We review outcomes of clinical trials that utilized a variety of MSP1 constructs and formulations, including MSP1_FL, either alone or in combination with other antigens, in both animal models and humans.

Expert opinion

Novel approaches to analyze breadth and magnitude of effector functions of MSP1-targeting antibodies in volunteers undergoing experimental vaccination and controlled human malaria infection will help to define correlates of protective immunity.

KEYWORDS:

• Plasmodium falciparum
• merozoite surface antigen 1
• vaccine development
• controlled human malaria infection
• asexual blood stage

Article highlights

• The critical and life-threatening consequences linked to Plasmodium falciparum malaria are directly attributable to the presence of asexual blood-stage parasites.

• Blood-stage malaria vaccines seek to diminish/impede the asexual reproduction of malaria parasites. Various clinical trials centered around P. falciparum blood-stage candidate vaccines have been performed but, regrettably, none has demonstrated robust protective effectiveness.

• Ongoing endeavors are concentrated on enhancing liver-stage vaccines which, in the event of not exhibiting sterile immunity, cannot safeguard against the potential advancement of liver-stage merozoites into asexual blood-stage parasites.

• The creation of a multi-stage malaria vaccine, combining liver-stage vaccines with an effective blood-stage vaccine, holds the promise of augmenting vaccine-driven protection against clinical disease.

• The merozoite surface protein 1 (MSP1) of P. falciparum is a major target of protective immunity and was initially considered an ideal malaria vaccine candidate.

• In monkey models, employing the complete MSP1 protein (MSP1_FL) for immunization, synergizing conserved domains from both the N- and C-terminal regions of MSP1, resulted in elevated levels of protection against live parasite challenge.

• MSP1 human trials have employed subunits or composite formulations comprising diverse smaller domains, but never the MSP1_FL, and exhibited poor performance.

• An MSP1_FL vaccine adjuvanted with GLA-SE has recently been tested for safety and immunogenicity in a first in human phase Ia trial involving malaria-naive volunteers.

• Antibodies generated through MSP1_FL vaccination demonstrated the ability to stimulate a diverse array of Fc-dependent effector functions in vitro.

• The logical progression entails delving into the connection between the spectrum of antibody multi-functionality and their effects on asexual blood-stage parasites in a CHMI model available for use in adult African populations.

Acknowledgments

The authors extend their heartfelt gratitude to the dedicated researchers, institutions, and study volunteers participating in malaria vaccine studies who have relentlessly pursued the formidable objective of jointly creating a malaria vaccine candidate centered around the merozoite surface antigen 1. The collective endeavors of the malaria research community have profoundly driven scientific advancements presented in this manuscript.

Declaration of interests

R Thomson Luque is employee of Sumaya-Biotech GmbH & Co. KG. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors have contributed to the conception and design of the review article and interpreting the relevant literature and have been involved in writing the review article or revised it for intellectual content.

Dedication

This review is dedicated to Prof. Herman Bujard, an inspiring scientist who, as a force of nature, drew everyone who interacted with him to join his passion to develop an MSP1-based malaria vaccine to protect vulnerable people living in malaria-endemic countries.

Data availability statement

The Plasmodium falciparum whole-genome assemblies used for this work are available from the NCBI (https://www.ncbi.nlm.nih.gov/gene/).

Disclaimer

The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of other entities.

Supplementary Material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14760584.2023.2295430

Additional information

Funding

Richard Thomson Luque is employed by Sumaya-Biotech GmbH & Co. KG that received support by the EU Malaria Fund. This work was supported in part by the U.S. National Institutes of Health (NIH) through awards R01 AI141900 and U19 AI110820 to JCS.