Vaccines 2021, 9, 1072. https://doi.org/10.3390/vaccines9101072 www.mdpi.com/journal/vaccines Review Plasmodium falciparum Malaria Vaccines and Vaccine Adjuvants Srinivasa Reddy Bonam 1, * ,† , Laurent Rénia 2,3,4, * ,† , Ganesh Tadepalli 5 , Jagadeesh Bayry 1,6 and Halmuthur Mahabalarao Sampath Kumar 5, * 1 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Equipe‐Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Université de Paris, F‐75006 Paris, France; jagadeesh.bayry@crc.jussieu.fr 2 A*STAR Infectious Diseases Labs, 8A Biomedical Grove, Singapore 138648, Singapore 3 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore 4 School of Biological Sciences, Nanyang Technological University, Singapore 308232, Singapore 5 Vaccine Immunology Laboratory, Organic Synthesis and Process Chemistry Division, CSIR‐Indian Institute of Chemical Technology, Hyderabad 500007, India; ganeshbabutmln@gmail.com 6 Biological Sciences & Engineering, Indian Institute of Technology Palakkad, Palakkad 678623, India * Correspondence: bsrpharmacy90@gmail.com (S.R.B.); renia_laurent@idlabs.a‐star.edu.sg (L.R.); sampath@iict.res.in (H.M.S.K.) † Equally contributed. Abstract: Malaria—a parasite vector‐borne disease—is a global health problem, and Plasmodium falciparum has proven to be the deadliest among Plasmodium spp., which causes malaria in humans. Symptoms of the disease range from mild fever and shivering to hemolytic anemia and neurological dysfunctions. The spread of drug resistance and the absence of effective vaccines has made malaria disease an ever‐emerging problem. Although progress has been made in understanding the host response to the parasite, various aspects of its biology in its mammalian host are still unclear. In this context, there is a pressing demand for the development of effective preventive and therapeutic strategies, including new drugs and novel adjuvanted vaccines that elicit protective immunity. The present article provides an overview of the current knowledge of anti‐malarial immunity against P. falciparum and different options of vaccine candidates in development. A special emphasis has been made on the mechanism of action of clinically used vaccine adjuvants. Keywords: anti‐malarial drugs; malaria vaccine; Plasmodium falciparum; vaccine adjuvants 1. Introduction Malaria, caused by apicomplexan Plasmodium spp., remains one of the world’s most threatening diseases of humans and other animals with high morbidity and mortality rates [1]. The recent findings of the World Health Organization (WHO) recorded 228 million cases and 405,000 deaths globally in 2018 [2]. Although eight species of Plasmodium can infect humans, most malarial cases are due to P. falciparum or P. vivax, but deaths are mostly due to falciparum malaria. The African countries carry the highest share of the global malaria burden (~90% as per 2017 WHO reports) [3]. In Asian countries, e.g., India, which accounts for 4% of the global burden, malaria is still a serious health threat [4]. As an answer, the Special Programme for Research and Training in Tropical Diseases (TDR; co‐sponsored by the WHO), US National Institutes of Health, UK department for international development, Bill & Melinda Gates Foundation, and other organizations have increased funding for research and development and other control measures (including vaccination) to minimize the malaria cases [2,5]. WHO has also put more effort into implementing essential malaria commodities, such as rapid diagnostic tests, insecticide‐treated mosquito nets, vector control, artemisinin‐based combination therapy, Citation: Bonam, S.R.; Rénia, L.; Tadepalli, G.; Bayry, J.; Kumar, H.M.S. Plasmodium falciparum Malaria Vaccines and Vaccine Adjuvants. Vaccines 2021, 9, 1072. https://doi.org/10.3390/ vaccines9101072 Academic Editors: Giampiero Girolomoni, Srinivasa Reddy Bonam and Jagadeesh Bayry Received: 14 August 2021 Accepted: 22 September 2021 Published: 24 September 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/license s/by/4.0/).