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 20th 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.
Highlights
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, a Gram-negative bacterium
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
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]
Summary
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. Extensive preclinical studies on animal models are essential to develop effective and safe vaccines especially ones with wide coverage. The present review article provides an overall glimpse of marketed meningococcal vaccines or the ones at preclinical stages of assessment or in clinical trials. 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 20th 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. 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
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