Meningococcal Vaccines Study

Immunogenicity, reactogenicity and persistence of meningococcal A, C, W-135 and Y-tetanus toxoid candidate conjugate (MenACWY-TT) vaccine formulations in adolescents aged 15–25 years. (Vaccine
Volume 27, Issue 1, 1 January 2009, Pages 161-168)


Development of meningococcal serogroups A, C, W-135 and Y conjugate vaccines could expand coverage against devastating meningococcal diseases. The immunogenicity of one dose of each one of five MenACWY-TT formulations versus a licensed ACWY polysaccharide vaccine was evaluated in 175 healthy subjects of 15–25 years. Serum bactericidal titers (rSBA) were evaluated before and after vaccination.

The percentage of rSBA responders to each serogroup A, C, W-135 and Y did not statistically differ from the control for each of the five formulations except for serogroup A that was lower after administration of one formulation. In the 3-year follow-up of the first study where the latter formulation was assessed, bactericidal antibody persistence was similar to the licensed ACWY polysaccharide vaccine for MenA and MenC and higher for MenW-135 and MenY.

Our results present five investigational MenACWY-TT conjugate vaccine formulations which are well tolerated and highly immunogenic in adolescents.

1. Introduction

Meningococcal disease due to Neisseria meningitidis remains a major public health problem worldwide due to the associated high levels of morbidity and mortality [1]. In Europe, from 1999 to 2006, the overall endemic incidence rate per 1,00,000 population ranged from 1.1 to 1.9 with the highest age specific incidence rates seen in children younger than 5 years of age, adolescents and young adults [2]. High risk groups include also those who live in crowded conditions, such as college campuses [3]. Mortality rates are generally highest in infants and young children, although very high mortality has also been recorded in adolescents [4]

Five serogroups (A, B, C, W-135 and Y), identified based on capsular polysaccharide (PS) antigens, are implicated in 95% of clinical meningococcal cases [5]. There is substantial regional variation in the relative distribution of each serogroup. In Africa and Asia, serogroups B and C cause sporadic disease, whereas serogroup A, and to a lesser degree serogroup C, are responsible for large-scale epidemics, with highest magnitude in the African meningitis belt [6]. Meningococcal meningitis epidemiology is also dynamic in time: serogroup W-135 has emerged as a new threat after causing outbreaks in Muslim pilgrims in Saudi Arabia and elsewhere, and then in Burkina Faso and Chad [7], [8] and [9]. Serogroup W-135 has now been isolated in numerous countries in Africa [10]; meningococcal disease due to serogroup X has been reported in Niger, where an outbreak occurred in 2006 [11]. In North America, serogroups B, C and Y are the major disease serogroups. By the mid-1990s, serogroup Y accounted for around one-third of all cases in the United States [12]. Cases of serogroup Y invasive disease have also been reported in Canada [13]. In Europe, serogroups B and C predominate, although the latter has been drastically reduced in those countries that have introduced meningococcal serogroup C conjugate vaccination [14].

No broadly protective vaccine exists against serogroup B meningococcal disease but effective vaccines against meningococcal disease due to the other four predominant serogroups are available, including the most recently developed meningococcal conjugate vaccines. Mass vaccination with serogroup C meningococcal conjugate vaccines has proven their effectiveness in all ages [15]. MenC conjugate vaccines are now given routinely in Australia, Canada and in some European countries either as infant vaccination followed by a booster or as a single dose in toddlers. Protection conferred by a single dose in adolescents or toddlers has been shown to last for at least 4–5 years [15] and [16] although bactericidal antibodies wane overtime in those vaccinated below 10 years of age, suggesting re-vaccination in adolescence may be necessary after vaccination in childhood [17]. Substantial reduction in nasopharyngeal carriage of serogroup C (66% reduction in adolescents in the UK [18] after MenC conjugate vaccination) is thought to be a major factor contributing to herd immunity after mass vaccination [19].

A cost-effectiveness study in Canada suggested that re-vaccination with a tetravalent conjugate vaccine would benefit those countries with established MenC conjugate vaccination programmes in light of possible increases in serogroup Y incidence [20]. Only one meningococcal ACWY conjugate vaccine is licensed to date (in the United States and in Canada) and several other meningococcal ACWY conjugate candidate vaccines are in clinical development [21].

This paper presents the results of two studies that evaluated the immunogenicity and reactogenicity of five formulations of a novel, combined MenACWY conjugate candidate vaccine that varied both in the amount of PS and the conjugation method for each serogroup. The vaccine formulations were administered as a single dose to teenagers and young adults.


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