Plasmodium falciparum circumsporozoite protein (CSP) and hepatitis B virus surface antigen (HBsAg) (CSP-HBsAg)

The Plasmodium falciparum circumsporozoite protein (CSP) and hepatitis B virus surface antigen (HBsAg) are the primary components of the first-generation and second-generation malaria vaccines, RTS,S/AS01 and R21/Matrix-M (Source: Nature, 2021). CSP is the most abundant protein on the surface of the malaria sporozoite and is essential for the parasite's motility and invasion of human hepatocytes (Source: UniProt P19597). In these vaccine formulations, the C-terminal and central repeat regions of CSP are fused to HBsAg, which self-assembles into virus-like particles (VLPs) that present the CSP epitopes in a highly repetitive, organized manner to the immune system (Source: Lancet, 2021). By targeting the pre-erythrocytic stage, these immunogens aim to prevent the development of blood-stage malaria, which is responsible for clinical symptoms and mortality. The inclusion of HBsAg not only provides a structural scaffold but also confers protection against the hepatitis B virus (Source: WHO, 2023). Clinical efficacy of these immunogens is highly dependent on the induction of high-titer antibodies against the NANP repeat region of CSP. These targets represent a significant milestone in global health, being the first to be used in a WHO-recommended malaria vaccine for children in endemic regions.

Other names

RTS,SR21Circumsporozoite proteinHBsAgCSPHepatitis B surface antigen

The immunogens function by inducing high-titer neutralizing antibodies against the CSP repeat region, which blocks sporozoite invasion of hepatocytes, and by stimulating T-cell responses; the HBsAg component serves as a scaffold for virus-like particle (VLP) formation to enhance immunogenicity (Source: WHO, 2023; PubMed: 34192535).