A review of combination adjuvants for malaria vaccines: a promising approach for vaccine development

[Display omitted] •Subunit malaria vaccines fail to induce strong and long-lasting immune responses.•Adjuvants are essential for generating stronger and protective subunit vaccines.•No single adjuvant is capable of eliciting protective immunity in a malaria vaccine.•Combination adjuvants are a potent approach to improvemalaria vaccine efficacy.•This review outlines the status of combination adjuvants in malaria subunit vaccines. It is obvious that there is a critical need for an efficient malaria vaccine to accelerate malaria eradication. Currently, recombinant subunit vaccination against malaria using proteins and peptides is gaining attention. However, one of the major drawbacks of this approach is the lack of an efficient and durable immune response. Therefore, subunit vaccines require adjuvants to make the vaccine sufficiently immunogenic. Considering the history of the RTS,S vaccine, it seems likely that no single adjuvant is capable of eliciting all the protective immune responses required in many malarial subunit vaccines and the use of combination adjuvants will be increasingly important as the science of malaria vaccines advances. In light of this, it appears that identifying the most effective mixture of adjuvants with minimal adverse effects offers tremendous opportunities in improving the efficacy of vaccines against malaria. Owing to the importance of a multi-adjuvanted approach in subunit malaria vaccine development, this review paper outlines some of the best known combination adjuvants used in malaria subunit vaccines, focusing on their proposed mechanisms of action, their immunological properties, and their notable results. The aim of the present review is to consolidate these findings to aid the application of these combination adjuvants in experimental malaria vaccines.