RSC Advances View Article Online REVIEW View Journal | View Issue A comprehensive overview of vaccines developed for pandemic viral pathogens over the past two Cite this: RSC Adv.,2021,11, 20006 decades including those in clinical trials for the current novel SARS-CoV-2 Kannan Damodharan, ab Gandarvakottai Senthilkumar Arumugam,b Suresh Ganesan,b Mukesh Doble *b and Sathiah Thennarasua The unprecedented coronavirus disease 2019 (COVID-19) is triggered by a novel strain of coronavirus namely, Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Researchers are working around the clock to control this pandemic and consequent waves of viral reproduction, through repurposing existing drugs as well as designing new vaccines. Several countries have hastened vaccine design and clinical trials to quickly address this outbreak. Currently, more than 250 aspirants against SARS-CoV-2 are in progress, including mRNA- replicating or non-replicating viral vectored-, DNA-, autologous dendritic cell-based-, and inactivated virus- Creative Commons Attribution-NonCommercial 3.0 Unported Licence. vaccines. Vaccines work by prompting effector mechanisms such as cells/molecules, which target quickly replicating pathogens and neutralize their toxic constituents. Vaccine-stimulated immune effectors include adjuvant, affinity, avidity, affinity maturation, antibodies, antigen-presenting cells, B lymphocytes, carrier protein, Received 13th November 2020 CD4+ T-helper cells. In this review, we describe updated information on the various vaccines available over the Accepted 14th January 2021 last two decades, along with recent progress in the ongoing battle developing 63 diverse vaccines against SARS- DOI: 10.1039/d0ra09668g CoV-2. The inspiration of our effort is to convey the current investigation focus on registered clinical trials (as of rsc.li/rsc-advances January 08, 2021) that satisfy the safety and efficacy criteria of international wide vaccine development. This article is licensed under a aDepartment of Organic and Bioorganic Chemistry, CSIR-Central Leather Research bBioengineering and Drug Design Lab, Department of Biotechnology, Indian Institute Institute (CLRI), Chennai, 600020, India of Technology Madras (IITM), Chennai, 600032, India. E-mail: mukesh.doble0@ gmail.com; [email protected] Open Access Article. Published on 08 June 2021. Downloaded 9/28/2021 7:21:02 PM. Kannan completed his B.Sc. Senthilkumar obtained chemistry degree at A. V. C. his M.Sc. chemistry at Bhar- College, Mayiladuthurai, affili- athidasan University, where he ated to Bharathidasan Univer- was involved in mechanistic sity, and M.Sc. in chemical studies of anticancer drugs. He sciences at Pondicherry Univer- then explored new drug sity, India. He obtained his PhD discovery and development from (organic chemistry) at the marine and medicinal plants, University of Madras, India. and their synthesis which is been Later, he took a research asso- developed at IIT Madras, IISc ciate position at the Department Bangalore and IIT Kanpur. He of Biotechnology, IIT Madras, developed variegated drug then moved to Taiwan for candidates at IIT Madras, such research at Tamkang University, Taiwan. Then he was employed as phosphate binder resin, sevcar (two patents); and tolvaptan, as a SERB-post-doctoral fellow at the CSIR-Central Leather hyponatremia and cystagon; and drugs from Terminalia arjuna. Research Institute, Chennai, India. He has synthesized substituted He then engaged in the peptidomimetic domain for antitumor alkynylated hybrid molecules and utilized them for NIR and EL screening at IISc Bangalore. Then back at IIT Madras worked on applications; and liquid crystalline-, steroidal-based materials for transitmycin, which is in phase-II pre-clinical trials. He has also sensor and biomedical applications; he also worked on the char- discovered new blood, breast, and liver cancer drugs, and diabetic acterization of natural product transitmycin. treatments. Recently, he also discovered, arjunetin, that is a better candidate for COVID-19 treatment than FDA approved drugs. 20006 | RSC Adv.,2021,11, 20006–20035 © 2021 The Author(s). Published by the Royal Society of Chemistry View Article Online Review RSC Advances Introduction Chemically, adjuvants are a highly heterogeneous group of compounds (including Al salts). One of the most successful therapeutic strategies to prevent or Antibiotics. Used in lower amounts during the develop- control various diseases is by “vaccination” protocol.1,2 Millions ment phase, to circumvent bacterial infection during tissue of lives have been saved because of vaccinations, which cover culture cells where the viruses are grown. MMR (measles, a number of diseases including certain types of cancer, HIV and mumps, rubella) and IPV (inactivated polio vaccine) associ- many viral infections.3 Vaccination was initially accomplished ated vaccines have a minimum amount (<25 mg) of neomycin by Edward Jenner, who was the pioneer for smallpox in the late for each dose. 18th century.4 In the 1980s, the development of vaccines to ght The MMR vaccine was developed by Maurice Hilleman in against pathogenic microorganisms was tentatively introduced. 1971. Mumps, like measles infections, are caused by an RNA Vaccines are now employed to improve and increase the based virus from the Paramyxoviridae family. Moreover, protection capability (immunity) of the body to ght severe measles and mumps belong to the genus Rubulavirus, it is infection and disease,5 and moreover, primarily intend to make a human disease with no animal reservoirs. Generally, the MMR ff immunity stronger and reduce resistivity of diseases by vaccine exhibits side e ects of a painful arm from the shot, reducing the reproduction of target pathogens. The majority of minor rashes, generally in teen/adult women who have no vaccines actively exist in the immune system, since anti-bodies earlier immunity; then the rubella vaccine component can ff are constantly generated in the body to sustain a healthy result in joint and tendon sti ness. This vaccine is also asso- immunity system.6,7 ciated with the minor threat of seizures/jerking instigated by fever, but is not connected with any enduring effects. The threat of febrile seizures increases as infants get older, hence this General components of vaccines vaccine is recommended at a young age. Some people may A vaccine consists of an antigen, stabilizer, adjuvant, antibiotic, experience cheek/neck inammation, impermanent low 8 Creative Commons Attribution-NonCommercial 3.0 Unported Licence. preservative, and chemical reagents such as formaldehyde. The platelet counts that generally do not require treatment and are advantages and disadvantages of vaccinations9a are listed in also not life threatening.9b Table 1. In 1955, Jonas Salk initiated an inactivated polio vaccine Antigen. The component matching the structural array of (IPV), aer that, Albert Sabin further developed the live, OPV. disease-oriented organisms, wherein, they are identied by the Even though poliovirus has three serotypes, both vaccines are immune system as ‘foreign’ and cause an active immune trivalent and offer good resistivity against poliomyelitis, response. a limited number of countries have continuously provided IPV. Stabilizer. This module is employed to assist the vaccine by Sabin’s OPV vaccine is underused in most countries due to sustaining its efficiency during storage. Instability of the minimising oral management, but it advances immunity in the This article is licensed under a vaccine can lead to reduced antigenicity and decreased infec- intestine, which is capable of spreading to others, and is asso- tivity of live attenuated vaccine (LAV). Magnesium chloride ciated with lower cost.9c (MgCl2) for oral polio vaccine (OPV), magnesium sulfate Preservatives. They are added in multi-dose vaccines, which Open Access Article. Published on 08 June 2021. Downloaded 9/28/2021 7:21:02 PM. (MgSO4) in measles vaccines, and lactose and gelatin associated can be used to control bacterial and fungal growth, including with sorbitol, are current representatives of stabilizing factors. thiomersal (sodium(2-carboxylatophenyl)sulfanyl-ethyl Adjuvant. They are responsible for enhancing the efficacy of mercury), formaldehyde, or phenolic derivatives. In fact, form- the vaccine by motivating the generation of antibodies. aldehyde is responsible for inactivating the viruses (e.g. IPV) and removing toxicity in bacterial strains, including the toxin employed in diphtheria and tetanus vaccines. Doble is a professor (Emeritus) in the Department of Biotechnology at the Indian Institute of Tech- Types of vaccines nology Madras (IITM). He Various kinds of vaccines are available and those which are worked for 23 years at Imperial administered to infants and adults can be classied (Fig. 1) as Chemical Industries and General follows: Electric Technology centers. His Live-attenuated. areas of interest are biomate- Inactivated. rials, drug design, bioreactors Toxoid. and bioremediation. He holds B. Conjugate. Tech and M. Tech degrees in Subunit. chemical engineering (IITM), and Live attenuated vaccines. These vaccines are adapted from a PhD (University of Aston, Bir- the existing bacteria or virus, they have been weakened, and mingham, UK) and has postdoctoral experience (University of thus will not result in serious disease in people with strong Cambridge, UK, and Texas A & M, USA). He has authored 320 immunity. LAV vaccines are more similar to the actual infec- technical papers, 10 books, and led 15 patents