Vol 14, Issue 4, 2021 Online - 2455-3891 Print - 0974-2441 PRECLINICAL STUDIES AND CLINICAL TRIALS IN DETERMINATION OF SAFETY AND EFFICACY OF MENINGOCOCCAL VACCINES: PRESENT SCENARIO SUTAPA BISWAS MAJEE 1* , SOUPAYAN PAL 2 1 Department of Pharmacy, NSHM Knowledge Campus, Kolkata-Group of Institutions, 124 B L Saha Road, Kolkata, West Bengal, India. 2 Department of Pharmaceutical Technology, Jadavpur University, Kolkata, West Bengal, India. Email: sutapabiswas2001@yahoo.co.in Received: 15 December 2020, Revised and Accepted: 27 January 2021 ABSTRACT Meningitis, a serious communicable inflammatory disease continues to be a worldwide threat especially in sub-Saharan Africa affecting millions of people with high death rates every year. Strains from six serogroups of the principal causative organism Neisseria meningitidis are found to be responsible for the majority of infections. Incidences of antibiotic resistance and efforts to provide mass protection have necessitated the development of meningococcal vaccines since the latter half of the 20 th century. Aiming to ostracize meningitis by 2030, the World Health Organization focuses on vaccination as an important strategy to reach the goal. Due to limited efficacy and stability issues of earlier polysaccharide and protein conjugate vaccines respectively, outer membrane vesicle (OMV) vaccines were developed. Gene manipulations have also led to the development of more efficacious tailor-made OMV vaccines due to over-expression of antigenic outer membrane proteins along with lesser pyrogenicity. Available data from preclinical studies in animal models and clinical trials, on meningococcal vaccine candidates report the strength of immune response measured by serological tests such as enzyme-linked immunosorbent assay and serum bactericidal assay. Post-immunization adverse reactions have been also monitored as a part of safety assessment. The novelty of the present review lies in summarizing the outcomes of the preclinical animal studies and clinical trials conducted on various types of meningococcal vaccines till date and thereby highlighting the paucities in the existing information which can facilitate understanding the present scenario, challenges, and future scope in the field of meningococcal vaccine development. Keywords: Animal studies, Clinical trials, Immune response, Meningitis, Outer membrane protein, Outer membrane vesicle vaccines, Serological tests. INTRODUCTION Meningitis, an inflammatory disease of the meninges remains to be a serious global public-health challenge with an estimated 1.2 million cases and 1,35,000 deaths each year caused by the major pathogen Neisseria meningitidis (meningococcus), a Gram-negative bacterium. Based on the chemistry of capsular polysaccharides 12 serogroups of N. menigitidis have been identified out of which six (A, B, C, W, X, and Y) are recognized to cause most of the meningococcal infections. Serogroups B and C are predominant, followed by serogroup A whereas the other three are emerging. Transmission of infection occurs from person to person through droplets of respiratory or throat secretions from carriers. The pediatric population is found to be most vulnerable with the highest attack rates in infants aged 3–12 months [1]. For treatment of meningitis infections, a range of antimicrobials has been prescribed by the European Society of Clinical Microbiology and Infectious Diseases, the Infectious Disease Society of America, and the World Health Organization (WHO) which include oily chloramphenicol injection (3 g single-dose intramuscular [i.m.]) [2], ceftriaxone i.m. or intravenous injection (2 g/day once daily for 5 days) [3], cefotaxime, amoxicillin, and gentamicin along with injectable dexamethasone (0.4 mg/kg every 12 h for 2 days) [4] for corticosteroid adjuvant therapy. However, mass vaccination to achieve herd immunity is the best rational approach to prevent pandemic situations and bring down the mortality rate especially in conditions of growing antibiotic resistance. From 2013 to 2020, 33 cases of penicillin-resistant N. meningitidis were reported from the United States, including 11 cases in 2019 to 2020 that were resistant to both penicillin and ciprofloxacin [5]. The Global Meningococcal Initiative recommendations advocate the use of conjugate vaccines to interrupt the acquisition of N. meningitidis [6] responsible for Invasive Meningococcal Disease that commonly includes meningitis and septicemia. Moreover, the WHO in its strategy “Defeating Meningitis by 2030: A Global Road Map,” (2020) puts much stress on vaccination during baseline situation thereby aiming to eradicate meningitis by 2030 [1]. Before clinical trials, extensive preclinical studies on animal models are essential to develop effective and safe vaccines especially ones with wide coverage. The WHO Guidelines on Nonclinical Evaluation of Vaccines followed by numerous National Regulatory Authorities of different countries deal with the necessary preclinical evaluation and highlight the requisite basic principles as well as specific guidelines for particular vaccines [7]. “European Agency for the Evaluation of Medicinal Products (EMEA) Note for Guidance on Preclinical Pharmacological and Toxicological Testing of Vaccines” provides protocols to determine efficacy and safety profiles of vaccine candidates [8]. Different publications [9-13] on meningococcal vaccines discretely put forward the studies and reports on individual vaccines designed so far with lacunae in information evident in several cases. However, no comprehensive work is available which can give a proper roadmap of meningococcal vaccine development from the latter half of the 20 th century till date. The present review article provides an overall glimpse of marketed meningococcal vaccines or the ones at preclinical stages of assessment or in clinical trials. Acquired knowledge can be helpful in understanding the progress, current status, challenges, and future scope in the domain of meningococcal vaccine development. Meningococcal vaccine types Exhaustive review of published reports on meningococcal vaccines reveals those which have been developed since 1974, that is, later half of the 20 th century against serogroups A, B, C, W, and Y [14]. Various meningococcal proteins such as GNA2091, GNA1030, Neisserial heparin-binding antigen, factor H binding protein (fHbp), NadA, Opc, Lbp, and PorA. have been exploited as antigenic targets in vaccine preparation [12]. A shift from mono- to multivalent vaccine has widened the protection coverage due to the presence of antigenic materials from more than one serogroup or strain. Before initiating the discussion on the present scenario of meningococcal vaccines, it is essential to understand the basic concepts pertaining to various classes of meningococcal vaccines categorized on the basis of their composition. © 2021 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/) DOI: http://dx.doi.org/10.22159/ajpcr.2021v14i4.40509. Journal homepage: https://innovareacademics.in/journals/index.php/ajpcr Review Article