Synthetic Toll-like receptor agonists for the development of powerful malaria vaccines: a patent review

ABSTRACT

Introduction: Currently, there is no efficient vaccine available against clinical malaria. However, continuous efforts have been committed to develop powerful antimalarial vaccine by discovery of novel antigens with in-depth understanding of its nature, immunogenicity, and presentation (delivery adjuvants). Moreover, another important part of vaccine development includes discovery of better immunostimulatory formulation components (immunostimulants). A protective vaccine against malaria requires antigen-specific B and T helper cell responses as well as cytotoxic T lymphocyte (CTL) responses. A long-lasting B and T memory cell production is also required for effective malaria vaccine. Since activation of Toll-like receptors (TLRs) promotes both innate inflammatory responses as well as the induction of adaptive immunity, several initiatives have been mounted during the last few years for the use of TLR agonists as malaria vaccine adjuvants.

Areas covered: The review summarizes reports related to the use and development of TLR agonists as malaria vaccine adjuvants and describes various strategies involved for the selection of specific antigens and TLR agonists.

Expert opinion: TLR agonists are promising adjuvants for the development of effective malaria vaccine, allowing for both innate inflammatory responses as well as the induction of adaptive immunity.

KEYWORDS:

• Malaria vaccine
• adjuvants
• TLR agonists
• P. facliparum
• TLRs
• pathogen associated molecular patterns (PAMPs)
• pattern recognition receptors (PRRs)

Article highlights

• The complex life cycle of plasmodium parasite and poorly immunogenic antigens have hampered the successful development of powerful malaria vaccine.

• Several new and multiple antigens or epitopes are being investigated along with variety of novel delivery systems and immunostimulating adjuvants.

• Subunit vaccine antigen or multiple antigens and/or epitopes combined with adjuvants targeting Toll-Like Receptor (TLR) elicit humoral and cellular responses necessary for a good vaccine candidate.

• The present review covers the technological findings of several research groups and clearly describes the various components of novel TLR-agonist adjuvanted malaria vaccine formulations and evaluation of its immunogenicity.

This box summarizes key points contained in the article.

Acknowledgements

DBS is thankful to UGC New Delhi for start-up research grant and DBT New Delhi for the award of Ramalingaswami Fellowship. The support from UGC-CAS, DST-PURSE-II, DST-SAIF and Panjab University Development fund is gratefully acknowledged. SS is a recipient of the IYBA Award from the Department of Biotechnology (DBT) and thankful to the Department of Science and Technology (DST), India, for financial support. Funding from the UPE II GRANT and DST PURSE, JNU is also acknowledged. AK is thankful to UGC, New Delhi for the award of Senior Research Fellowship. DK acknowledges the Shiv Nadar University for providing the research fellowship. The contribution of Ms. Amrita Chakrabarti, Research Scholar, Department of Life Science, Shiv Nadar University, Uttar Pradesh, India for revising the manuscript draft is gratefully acknowledged.

Declaration of interest

DBS is supported by UGC New Delhi for start-up research grant and DBT New Delhi for the award of Ramalingaswami Fellowship. The support from UGC-CAS, DST-PURSE-II, DST-SAIF and Panjab University Development fund is gratefully acknowledged. AK is supported by UGC, New Delhi for the award of Senior Research Fellowship. SKM receives financial support from PURSE Grant (II). SS is a recipient of the Innovative Biotechnologist Award (IYBA) from the Department of Biotechnology, New Delhi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was funded.