Meningococcal Vaccine

Meningococcal Serogroups

At least 13 different N. meningitidis serogroups have been defined on the basis of their immunological reactivity and structure of the capsule’s polysaccharide. These serogroups are the following: A, B, C, E-29, H, I, K, L, W-135, X, Y, Z, and Z’(29E). Six of these serogroups cause disease: serogroups A, B, C, W-135, X, Y.

• N. meningitidis serogroup A (MenA)

Serogroup A was the cause of most meningococcal disease in the first part of the twentieth century in developed countries, but it is now rare in the US and Europe. Nowadays, epidemics of disease caused by MenA occur in the meningitis belt of sub-Saharan Africa as well as in southeastern Asia. This region of sub-Saharan Africa encompasses parts or the whole of 26 countries and extends from Senegal in the West to Ethiopia in the East. Historically, incidence rates in this region have exceeded 800 cases per 100,000 population per year during serogroup A meningitis epidemics.

• N. meningitidis serogroup B and C (MenB, MenC)

MenB and MenC are responsible for most diseases in Europe and North America and account for 30% of disease in the US and Europe. Serogroup B polysaccharide is poorly immunogenic, but serosubtype-specific vaccines have been developed for countries such as Cuba, New Zealand, and Norway that have experienced prolonged epidemic serogroup B disease. These vaccines are based on strain-specific outer membrane vesicle (OMV) preparations and were successful in reducing the incidence of local serogroup B outbreaks.

• N. meningitidis serogroup W (MenW)

Serogroup W-135 has emerged in the last 20 years as a cause of epidemic disease. It is responsible for an epidemic that occurred during the Hajj pilgrimage to Mecca nearly two decades ago. Serogroup W-135 has also emerged in parts of Africa and South America. Burkina Faso in particular witnessed a large outbreak of serogroup W-135 infection in 2002.

• N. meningitidis serogroup Y (MenY)

MenY has been increasing in incidence in North America and Europe and caused more than a quarter of the disease due to meningococci in the US in the last decade. Serogroup Y causes meningococcal pneumonia in older adults, but is also responsible for a large proportion of meningococcaemia and meningitis among infants less than 6 months of age. Serogroup Y has also been seen recently in South Africa, South America, and Israel.

• N. meningitidis serogroup X (MenX)

MenX has recently been found responsible for meningococcal cases and outbreaks in certain African countries such as Kenya, Niger, and Ghana.

Current Vaccines against Neisseria meningitidis

Meningococcal vaccines are highly effective at protecting against different strains of the meningococcal bacteria. There are a number of vaccines that are approved to target five of the six disease-causing serogroups of the pathogen.

• Polysaccharide-based vaccines

There are polysaccharide-based and glycoconjugate vaccines for serogroup A, C, W and Y. The polysaccharide-based vaccines have been licensed since the 1970s, as mono-, bi-, tri- and tetravalent vaccines, in various formulations containing MenA, MenC, MenW and MenY CPS. The currently administered polysaccharide-based vaccines are quadrivalent containing CPS from serogroups A, C, W and Y. Mencevax (GlaxoSmithKline, Belgium) is licensed for use in Europe while Menomune (Sanofi Pasteur, Swiftwater, PA, USA) is licensed for use in the United States and Canada. Polysaccharide vaccines are primarily used in cases of epidemics and outbreaks. A short-lived, T cell-independent immune response is generated from immunization with this class of vaccines. Due to the longer lasting effect of glycoconjugate vaccines, these polysaccharide-based vaccines have been replaced.

Fig. 2 Polysaccharide molecular structures and conjugation technology of licensed meningococcal group A, C, W135, and Y conjugate vaccine produced by Novartis Vaccines (Costantino P, et al. 2011)

Conjugate vaccines are more immunogenic, provide longer immunity, and are more effective at inducing herd immunity than polysaccharide vaccines. Glycoconjugate vaccines use microbial capsular polysaccharides covalently linked to a carrier protein. After isolation of purified meningococcal capsular polysaccharide, it is subjected to acid hydrolysis to obtain smaller oligosaccharide fragments. Chemical structures of the monosaccharide units of meningococcal polysaccharides for which there are currently glycoconjugate vaccines are given in Figure 2. Three major types of carrier proteins have been used in vaccines against Neisseria meningitidis: diphtheria toxoid (DT), non-toxic mutant of diphtheria toxin (CRM197), and tetanus toxoid (TT). There are currently three monovalent conjugate vaccines licensed for MenC (Pfizer and GSK) and one monovalent vaccine against MenA (Serum Institute of India). Meningococcal multivalent glycoconjugate vaccines naturally provide broader coverage than monovalent vaccines. These vaccines include Menveo (GSK), Menactra (Sanofi), Nimenrix (Pfizer), MenHibrix and Menitorix (GSK).

• Outer membrane vesicle-based (OMV) and protein-based vaccines

Since vaccines based on MenB polysaccharides have poor immunogenicity, non-polysaccharide components have been used as potential MenB vaccines. OMVs contain phospholipids, lipooligosaccharides, and membrane proteins. All of those components alone can be antigens that are recognized by host antibodies. A novel approach called "reverse vaccinology" was used to identify putative protective antigens as vaccine candidates by using bioinformatics algorithms. Some promising candidates were identified using the method. Bexsero (GSK) contains OMV from NZ98/254 (an outbreak-specific strain), rNHBA (a recombinant Neisseria heparin binding antigen) fusion protein, rNadA (recombinant Neisseria adhesin A), rfHbp (a recombinant complement factor H binding protein). Trumenba (Wyeth), on the other hand, is composed of two lipidated antigenic variants of rfHbp factors.