Immunogenicity of Malaria Vaccine Candidates

Efforts to develop a broadly effective malaria vaccine have centred on eliciting potent and durable immune responses against key parasite antigens at both the liver (pre-erythrocytic) and blood stages. Pre-erythrocytic candidates, notably the circumsporozoite protein (CSP) and a range of traversal and surface proteins, aim to block hepatocyte invasion and forestall blood-stage replication. Blood-stage approaches target merozoite antigens to curb erythrocyte infection and reduce disease severity. The principal immunological correlates of protection include high titres of functional antibodies, robust CD4+ and CD8+ T-cell responses, and the generation of long-lived memory B cells. Adjuvant formulation plays a decisive role in shaping the magnitude, isotype profile and durability of these responses. Advances in multi-valent antigen design and novel delivery platforms, such as virus-like particles and liposomal constructs, have sought to overcome challenges of antigenic polymorphism, waning immunity and strain specificity. Integration of immunogenicity data from natural infections with controlled human malaria infection models has further guided rational vaccine design and optimisation of dosing regimens.

Research from Nature Portfolio

Recent studies have characterised naturally acquired antibody responses to multiple pre-erythrocytic antigens beyond CSP, revealing that antibodies against CelTOS and SPECT1 inhibit sporozoite invasion of human hepatocytes in vitro as effectively as anti-CSP. This work emphasises the value of multi-valent vaccines incorporating conserved traversal antigens. In parallel, a novel virus-like particle vaccine has demonstrated sterile protection in rodent models against transgenic challenge with distinct CSP alleles. Protective immunity correlated with IgG2a responses in the absence of detectable antigen-specific T cells, and cross-allelic efficacy was achieved by combining VK210 and VK247 CSP variants. These findings underscore the promise of VLP platforms and cross-strain antigen design in pre-clinical evaluation.

Immunogenicity of Malaria Vaccine Candidates publication trend

The graph below shows the total number of articles in immunogenicity of malaria vaccine candidates across all publications each year (not limited to Nature Index journals).

Technical terms

Pre-erythrocytic stage: The initial phase of malaria infection when sporozoites invade hepatocytes prior to blood-stage replication.

Circumsporozoite protein (CSP): A dominant surface antigen on sporozoites and a leading vaccine target for blocking liver infection.

Virus-like particle (VLP): A non-infectious nanostructure that mimics viral architecture to present antigens and enhance immunogenicity.

Adjuvant: A formulation component that amplifies and modulates the immune response to a vaccine antigen.

Memory B cell: A long-lived lymphocyte that rapidly differentiates into antibody-secreting cells upon antigen re-exposure.

References

1. Poly I:C elicits broader and stronger humoral and cellular responses to a Plasmodium vivax circumsporozoite protein malaria vaccine than Alhydrogel in mice. Frontiers in Immunology (2024).
2. A CAF01-adjuvanted whole asexual blood-stage liposomal malaria vaccine induces a CD4+ T-cell-dependent strain-transcending protective immunity in rodent models. mBio (2023).
3. Naturally acquired antibodies against Plasmodium vivax pre-erythrocytic stage vaccine antigens inhibit sporozoite invasion of human hepatocytes in vitro. Scientific Reports (2024).
4. Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models. Scientific Reports (2017).
5. Longitudinal analysis of antibody responses to Plasmodium vivax sporozoite antigens following natural infection.. PLOS Neglected Tropical Diseases (2024).