Advancements and Challenges in Developing Malaria Vaccines: Targeting Multiple Stages of the Parasite Life Cycle

Abstract

Malaria, caused by Plasmodium species, remains a major global health concern, causing millions of deaths annually. While the introduction of the RTS,S vaccine has shown promise, there is a pressing need for more effective vaccines due to the emergence of drug-resistant parasites and insecticide-resistant vectors. However, the complex life cycle and genetic diversity of the parasite, technical obstacles, limited funding, and the impact of the 2019 pandemic have hindered progress in malaria vaccine development. This review focuses on advancements in malaria vaccine development, particularly the ongoing clinical trials targeting antigens from different stages of the Plasmodium life cycle. Additionally, we discuss the rationale, strategies, and challenges associated with vaccine design, aiming to enhance the immune response and protective efficacy of vaccine candidates. A cost-effective and multistage vaccine could hold the key to controlling and eradicating malaria.

Immunogenicity of PvCyRPA, PvCelTOS and Pvs25 chimeric recombinant protein of Plasmodium vivax in murine model

“…Compared with other findings in the malaria literature, MF59/AddaVax performed lower IgG titers with approximately 10x10 2 for PfMSP antigen (52), when compared with our data. Another finding is closer to our results, presenting approximately a 10x10 4 for PvDBP antigen (50). Regarding Al(OH) 3, this adjuvant performed lower immunogenicity in a study that related a similar response when compared to our findings, varying between 10x10 4 and 10x10 5 for the transmission-blocking candidate Pfs230d1 (44).…”

“…In the field of malaria vaccine development, strategies are focused around the Plasmodium biological cycle, aiming to stimulate stage-specific immune responses ( 4 , 5 ). These approaches include pre-erythrocytic strategies to neutralize sporozoites and prevent hepatocyte invasion ( 6 , 7 ), erythrocytic vaccines to inhibit merozoite invasion and multiplication ( 8 – 10 ), and transmission-blocking vaccines against sexual stages to impede mosquito infectivity ( 11 , 12 ).…”

Persistence of Anti-SE36 Antibodies Induced by the Malaria Vaccine Candidate BK-SE36/CpG in 5–10-Year-Old Burkinabe Children Naturally Exposed to Malaria

“…The release of merozoites from the liver leads to blood-stage infection, and the subsequent continuous cycles of erythrocyte invasion and rupture is responsible for clinical disease. A number of parasite proteins unique to this stage are expressed [ 4 , 15 ]. Challenges in developing vaccines that target the erythrocytic stage include (i) extensive genetic polymorphism/large allelic variation; (ii) the functionally redundant pathways/proteins involved in parasite invasion; and (iii) the stimulation of host immune effector mechanisms allowing the parasite to escape/subvert the host immune system [ 2 , 4 , 6 , 15 , 16 ].…”

“…A number of parasite proteins unique to this stage are expressed [ 4 , 15 ]. Challenges in developing vaccines that target the erythrocytic stage include (i) extensive genetic polymorphism/large allelic variation; (ii) the functionally redundant pathways/proteins involved in parasite invasion; and (iii) the stimulation of host immune effector mechanisms allowing the parasite to escape/subvert the host immune system [ 2 , 4 , 6 , 15 , 16 ]. Children under 5 years of age are more susceptible to severe malaria than older children; and pre-existing immunity in older children and adults impacts vaccine efficacy [ 17 , 18 ].…”