January 20, 2023
Malaria parasite (Plasmodium falciparum) is a major public health concern, with children under 5 years old in Sub-Saharan Africa accounting for most of infections: in Africa, a child dies from malaria every minute. Only in 2020, there were an estimated 241 million cases of malaria worldwide, causing over 627 000 deaths; children under the age of 5 accounted for around 80% of all malaria deaths in the African Region.
The world’s first malaria vaccine, RTS,S/AS01, was recently recommended by the World Health Organization (WHO) for widespread use. However RTS,S/AS01, has modest efficacy of up to only 36% against this disease, and therefore, the development of a second-generation malaria vaccine with greater efficacy and longevity is urgently needed.
A major impediment to developing a highly efficacious vaccine is the polymorphic nature of Plasmodium falciparum antigens which alter epitope antibody responses leading to low or limited protection. The N-terminal domain (SE36) of the serine repeat antigen 5 (SERA5) was selected for further development as it shows limited polymorphism and has immunodominant IgG epitopes not requiring strict tertiary structures to elicit protective immunity. Recombinant SE36 was formulated with aluminum hydroxide gel to yield the blood-stage malaria vaccine candidate BK-SE36, currently under clinical evaluation in EVI-led consortium SEmalvac.
BK-SE36 has already been used in phase Ib randomised trials conducted in Uganda and Burkina Faso, that showed that the vaccine was safe and immunogenic[1]. The present study examines the genetic diversity of SERA5 in Africa and the role of allele/variant-specific immunity, with sequence analyses performed on strains collected from the two clinical trial/follow-up studies, and cross-sectional studies in Africa.
Compared to other highly polymorphic vaccine candidate antigens, polymorphisms in SERA5 were largely confined to the repeat regions of the gene, with differences observed among isolates from the four African countries. While mismatches with the vaccine-type SE36 were observed, the haplotype diversity of SERA5 was similar between vaccinated and control participants, with antibodies induced by BK-SE36 vaccination binding epitopes located in the disordered regions of the protein. The results indicate that BK-SE36 does not elicit an allele-specific immune response, but that young children or individuals with limited malaria infection history would respond better to BK-SE36.
In summary, Africa-specific strain variations in SERA5 did not appear to influence the effectiveness of BK-SE36 to elicit an immune response. These results indicate that BK-SE36 is a promising vaccine candidate for infants.
Read full publication: https://doi.org/10.3389/fcimb.2022.1058081
[1] Bougouma, E. C., Palacpac, N. M. Q., Tiono, A. B., Nebie, I., Ouédraogo, A., Houard, S., et al. (2022). Safety and immunogenicity of BK-SE36 in a blinded, randomized, controlled, age de-escalating phase ib clinical trial in Burkinabe children. Front. Immunol. 13, 978591. doi: 10.3389/fimmu.2022.978591
See more about SEmalvac project here: https://www.euvaccine.eu/malaria-vaccines/SEmalvac
Click here to view the MVIP / RTS,S infographic with new malaria figures from the World Malaria Report 2021
This work was supported by the Global Health Innovative Technology Fund (G2014-109) https://www.ghitfund.org/investment/portfoliodetail/detail/99
Photo by Annie Spratt on Unsplash