Viral-Vectored Vaccines for Malaria Immunization

Viral-vectored vaccines harness replication-deficient viral carriers to deliver malaria antigens and elicit robust cellular and humoral immunity. This approach has advanced pre-erythrocytic and blood-stage strategies by encoding key targets such as circumsporozoite protein (CSP), thrombospondin-related adhesion protein (TRAP) and apical membrane antigen 1 (AMA1). Heterologous prime-boost regimens using simian adenovirus and Modified Vaccinia Ankara (MVA) overcome anti-vector immunity and yield high frequencies of antigen-specific CD8+ T cells, correlating with sterile protection in controlled human malaria infection studies. Innovative platforms, including attenuated vaccinia strains and adeno-associated virus constructs, now extend scope to Plasmodium vivax and multistage vaccines. Pre-clinical and clinical findings demonstrate durable immunity, reduction of liver-stage parasite burden and transmission-blocking activity. Integration into existing immunisation programmes, combined with flexible dosing intervals, supports global roll-out. These vectors offer a modular framework to incorporate emerging antigens, address diverse Plasmodium species and contribute to the ultimate goal of malaria eradication.

Research from Nature Portfolio

Recent studies have refined heterologous prime-boost regimens with simian adenovirus and MVA vectors expressing the multiple epitope-TRAP (ME-TRAP) antigen. Alternative dosing intervals enhanced CD8+ T cell magnitude without increasing reactogenicity, informing optimal schedules for phase II trials. A comparative evaluation of ten pre-erythrocytic antigens delivered by ChAd63 and MVA vector systems identified novel liver-stage candidates—LSA1 and LSAP2—that confer sterilising immunity in murine models, broadening the antigenic repertoire beyond classical targets. These findings underscore the potential of viral platforms to screen and validate new antigens that drive protective cellular responses.

Viral-Vectored Vaccines for Malaria Immunization publication trend

The graph below shows the total number of articles in viral-vectored vaccines for malaria immunization across all publications each year (not limited to Nature Index journals).

Technical terms

Viral vector: A genetically engineered virus used as a carrier to deliver antigen-encoding genes into host cells without causing disease.

Heterologous prime-boost: A vaccination strategy using two different vector platforms in sequence to enhance immune responses by reducing anti-vector immunity.

CD8+ T cell: A subset of lymphocytes that recognise antigenic peptides presented by MHC class I and mediate cytotoxic killing of infected cells.

Pre-erythrocytic stage: The phase of malaria infection when sporozoites infect hepatocytes before progressing to blood-stage replication.

Transmission-blocking: Vaccine-induced inhibition of parasite development in mosquitoes to prevent onward transmission from vaccinated hosts.

Circumsporozoite protein (CSP): The major surface protein of malaria sporozoites, a key target for pre-erythrocytic vaccine-induced immune responses.

Thrombospondin-related adhesion protein (TRAP): A conserved malaria antigen involved in sporozoite motility and hepatocyte invasion, eliciting T cell responses.

References

1. A two-dose viral-vectored Plasmodium vivax multistage vaccine confers durable protection and transmission-blockade in a pre-clinical study. Frontiers in Immunology (2024).
2. Recent Advances in the Development of Adenovirus-Vectored Vaccines for Parasitic Infections. Pharmaceuticals (2023).
3. Assessment of novel vaccination regimens using viral vectored liver stage malaria vaccines encoding ME-TRAP. Scientific Reports (2018).
4. Comparative assessment of vaccine vectors encoding ten malaria antigens identifies two protective liver-stage candidates. Scientific Reports (2015).
5. Evaluation of the Efficacy of ChAd63-MVA Vectored Vaccines Expressing Circumsporozoite Protein and ME-TRAP Against Controlled Human Malaria Infection in Malaria-Naive Individuals. The Journal of Infectious Diseases (2014).
6. Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation. Nature Communications (2013).
7. Phase Ia Clinical Evaluation of the Safety and Immunogenicity of the Plasmodium falciparum Blood-Stage Antigen AMA1 in ChAd63 and MVA Vaccine Vectors. PLOS ONE (2012).