Neisseria meningitidis resides in its natural habitat within the nasopharyngeal tract of humans [29]. 5-15% of the human population carries the bacteria in its nonpathogenic form [29]. A major step in infection is its colonization in the nasophrynx of the human carrier [29]. After colonizing the nasopharynx, the bacteria adhere to pili and cross the nasopharyngeal epithelium by a process of endocytosis to invade the circulatory system [23,29]. In the bloodstream, the bacteria proliferate and adapt to the host environment. Clinical responses to infection are varied from a benign form to extreme, fatal forms (meningococcaemia) [29]. In its most severe form, heightened levels of bacteria in the blood make their way to the meninges in the brain and at such high levels of cytotoxicity, induce inflammation of the meninges and progression of the disease [23]. Persons most susceptible to the infection are often immunocompromised, suffering from various medical conditions (i.e. head trauma and diseases associated with immunosuppression such as HIV). Others acquire infection through close contact with a primary carrier, and infection is also common among persons with deficiencies in the terminal common complement pathway (C3, C5-C9) [27]. Persons may develop natural immunity by carrying a nonpathogenic form of N. meningitidis in their nasopharyngeal tract.

The carbohydrate capsule of N. meningitidis determines its virulence and is targeted by the immune system. Approximately 12 strains of N. meningitidis exist and are characterized by the polysaccharide expressed on its capsule: A, B, C, 29-E, H, I, K, L, W-135, X, Y and Z. Serogroups A, B and C cause 90% of meningococcal meningitis cases, while group B accounts for approximately half of these [25,26]. The carbohydrate component of the capsular membrane induces a T-independent immune response. Thus, neither long term immunity by memory cell formation nor antibody affinity maturation is observed. Rather than being engulfed and processed by an antigen presenting cell (APC), the large carbohydrate capsule interacts directly with B cells. This interaction with the B cell causes production of serogroup specific antibodies, primarily IgM. IgG is also produced with an IgG1 response predominating in children and an IgG2 response predominating in adults. The immune systems of infants are not sufficiently developed to achieve an immune response to the polysaccharide membrane (CHO component), which accounts for the prevalence of meningitis in this age group [14].

IgA secretions, the complement pathway and phagocytosis are among the immune responses that N. meningitidis evades [23]. The bacteria produce IgA1 proteases which cleave IgA at either proline-threonine or proline-serine bonds [23,24], while the polysaccharide capsule renders it resistant to macrophage phagocytosis, permitting it to evade the complement pathway [23]. Moreover, large amounts of Lipopolysaccharide (LPS) endotoxin are released by the bacteria to induce toxic shock and hemorrhaging [23]. Lastly, leukotriene B4, a chemotatic factor synthesized in peripheral mononuclear cells (PMN), is also suppressed [24].

The meningococcal vaccines currently approved for use in humans are made from the variant, purified capsular polysaccharides, which are characteristic of the bacteria membrane[29]. Such vaccines are most effective against serogroups A and C although, in the United States, a quadrivalent vaccine containing four types of meningococcal bacteria (against serogroups A, C, Y, W-135) has proven to be 75-90% effective among people over two years of age [27]. Of the population vaccinated, immunity has been shown to last approximately three years [27]. Unfortunately, such capsular polysaccharide vaccines present serious limitations as they have no effect on children less than two years of age and the immune response is short-lived in older children and youths [29]. Further, uncertainty is added due to the ability of the meningococcal bacteria to perform switches of its capsule type [29].

Conjugate vaccine technology has shed new light on the development of a more effective vaccine [29]. This technique involves the conjugation of a carrier protein covalently linked to a purified capsular polysaccharide. The presence of the protein carrier effectively elicits the T-dependent response, achieving immunological memory and antibody affinity maturation even in the young (less than eighteen months of age). This is advantageous in that such a response is absent in vaccinations with the purified capsular polysaccharide alone [29].

A protein based vaccine against serogroup B is also under development [25]. The development of a vaccine against serogroup B poses the biggest problem due to the similarity between the B capsular polysaccharide structure and a polysialic acid containing glycopeptides that are a part of human brain tissue [14]. This similarity induces immunogenic tolerance to the B capsular coat [14]. Due to the setback posed by the group B serogroup, studies are currently underway to develop cross-reactive carbohydrate epitopes from other bacterial species that might induce an immune response and overcome immunogenic tolerance. Researchers would also like to alter the immunological nature of the carbohydrate (CHO) antigen from T-independent to T-dependent, by conjugating the CHO antigen to a protein carrier [14]. This conjugate vaccine technique (described above) has been used to conjugate a chemically altered polysialic acid from an E. Coli strain (K1) to a purified recombinant meningococcal porin [14]. In preclinical studies, this vaccine successfully elicited bacteriacidal antibodies (anti-serogroup B) in both mice and nonhuman primates [14]. Conjugate vaccines for N. meningitidis have exhibited immunogenicity even in the very young and are currently at various stages of clinical evaluation [14]. This technology is also being applied to improve other vaccines relevant to serogroups A and C, which are also under development [14].

Promising studies have also been conducted on the development of a vaccine based on major class proteins derived from N. meningitidis strains [29]. Class 1 protein has been shown to induce protective type-specific bacteriacidal antibodies in animal models [29]. With the application of recombinant DNA technology, a vaccine has been constructed, carrying several of these class 1 proteins derived from six different strains [29]. The resultant hexavalent vaccine has proven to be most promising and has passed phase I clinical trials in humans, confirming its safety and observed development of bacteriacidal antibodies against all six bacteria strains [29]. Phase II trials are currently underway and being carried out in children [29].

The most suitable therapy is antimicrobial chemoprophylaxis. If not administered within the first fourteen days after infection, therapy is of limited or no value [27]. Chemoprophylaxis is most effectively used to prevent meningococcal colonization in people in proximity with persons affected by meningococcal disease [29]. Rifampin which is most effective in eradicating nasopharyngeal carriage of N. meningitidis, is the drug of choice administered to close contacts upon diagnosis of the primary case but should not be taken during pregnancy [27,29]. Similarly, ciprofloxacin and ceftriaxone may be used as alternatives to rifampin, but should not to be used by children less than eighteen years of age or by pregnant and lactating women [28]. Penicillin G, ampicillin, chromphenicol, oily chloromphenicol, and ceftriaxone are the drugs commonly used in antibiotic therapy [28].