New Zealand has experienced an epidemic of serogroup B meningococcal infection since 1991 (1), which has so far been responsible for more than 4700 cases and over 200 deaths (2). The overall incidence reached a high of 17.4 cases per 100 000 population in 2001. In 2002, incidence rates for Maori and Pacific Islands children <1 year of age were 286 and 368 per 100 000 respectively (2). The New Zealand Health authorities asked the World Health Organization (WHO) for assistance, and in 1993 an international advisory group was established. Various options were evaluated, and in 2000 a proposal for vaccine development and manufacture, followed by performance of clinical trials, from the Norwegian Institute of Public Health (NIPH) and Chiron Vaccines (Siena, Italy) (CV), was accepted (3). The proposal was to prepare a protein based, outer membrane vesicle (OMV) vaccine from a wild-type strain typical of that causing the epidemic in New Zealand.

Conventional capsular polysaccharide (PS) meningococcal vaccines against serogroup A, C, Y, and W135 disease have existed since the late 1960s (3, 4). Recently successful attempts have shown that it is possible to formulate conjugate vaccines with the respective capsular polysaccharides (3). The major impact on disease following introduction of the C-conjugate vaccine in the United Kingdom (UK) has led to licensure of this vaccine in several countries and gives hope for the development of improved formulations of other meningococcal vaccines (3). The group B polysaccharide, however, is not suitable as a vaccine, mainly because it is non-immunogenic in humans. Thus, most approaches for vaccine development against group B meningococcal disease have focused on various outer membrane proteins as vaccine candidates (3, 5).

Group B meningococcal strains show substantial variation at the pheno- and genotypical level (3, 6, 7). During an epidemic, however, the strains causing the outbreak normally belong to the same clonal population. This was the case during the epidemics in Cuba and Norway in the 1980s (8, 9), in Chile from the mid 1990s (10) and currently in New Zealand (1). In New Zealand the outbreak is caused by the hyper-virulent lineage III-clone, characterised as B:4:P1.7-2,4 and ST42 or ST154 which are subclones of the ST44 complex (1, 11).

The OMV vaccine was developed with reference to the Norwegian meningococcal group B vaccine, MenBvac (12, 13). The vaccine was prepared from a B:4:P1.7-2,4 New Zealand strain by fermenter growth and extraction with the detergent deoxycholate to yield OMVs which were adsorbed to aluminium hydroxide. Manufacture and preclinical testing of such OMV vaccines have recently been described (14).

For evaluation of safety, reactogenicity, and immunogenicity, phase I/II trials in adults, 8-12 year-old children, toddlers (18-24 months), and infants are being performed in rapid succession (15). Three doses of the vaccine are being given six weeks apart. The first step of the successive trials included 75 adult subjects. Preliminary results suggest that the vaccine is safe and similar reactogenicity was observed as for the parent vaccine, MenBvac. The remaining trials are each expected to include about 300 subjects. Clinical trials in 8-12 year-old children and in toddlers are ongoing, and further vaccination in larger groups of children and infants are planned. Based on data from a clinical trial using MenBvac in Chile, a good immune response in younger children and in infants is expected against the homologous strain (10). After rollout of vaccine to all New Zealanders under 20 years of age (expected to begin in 2004) the vaccine may be included in the national immunisation schedule at least until the epidemic is controlled. The serum immune responses of vaccinees are being evaluated by measuring antibodies specific to OMV in enzyme-linked immunosorbent assay (ELISA), and by testing for serum bactericidal activity (SBA) in sera from vaccinees. The SBA test is a functional assay, considered to correlate with protection against meningococcal disease (4, 16). Collaboration between four laboratories (in New Zealand, USA, the UK, and Norway) has been established for standardisation and comparison of SBA for the meningococcal group B.

In 1996 polymerase chain reaction (PCR) tests for meningococcal deoxyribonucleic acid (DNA) became available and the use of this method has increased. In 2002, 557 cases of meningococcal disease were reported in New Zealand, of which 413 (74.1%) were laboratory confirmed (2) and 31.8% of the cases, unconfirmed by culture, were confirmed by PCR. Of the 384 cases for which this could be measured, either by serotyping of an isolate or genotyping of DNA from patient specimens, 297 (77.3%) were caused by the serogroup B epidemic strain expressing the PorA P1.7-2,4 subtype (2).

The group B meningococcal epidemic in Norway in the 1980s persisted for more than 10 years. In an attempt to predict the progress of the epidemic in New Zealand, the number of cases in Norway (population 4.5 million) and the registered cases in New Zealand (population 3.3 million) have been shown together in the figure below.

Figure. Meningococcal disease cases by number of years from pre-epidemic period (equivalent year) for Norway and New Zealand. Graphical illustration of the two different group B meningococcal epidemics in Norway [1970/80's] and in New Zealand [at present] (2).

Vaccine will be offered to each age group of the wider population depending on the ability to mount a homologous immunologic response to the 'tailor made' vaccine. A large body of safety data with the NIPH Norwegian strain vaccine and similar vaccines is available and surveillance of adverse events in 'real time' is planned. Public Health legislation in New Zealand allows rapid evaluation for provisional vaccine licence in response to an epidemic.

A collaborative alliance between two governmental organisations located on the opposite side of the globe and a vaccine manufacturer in Italy has resulted in a 'tailor made' vaccine for controlling the ongoing epidemic in New Zealand. The collaboration has managed to design and perform a public health intervention in New Zealand for evaluation of vaccine efficacy, rather than undertaking a traditional randomised controlled clinical trial. Provided that the remaining trials produce positive results, and anticipating a population rollout starting from early 2004, a preventive effect in the population might be noticeable late 2004 or during the first half of 2005. If successful, the concept of using 'tailor made' OMV vaccines might enable rapid response to similar epidemic scenarios that are likely to surface in other parts of the world in the coming years.

The New Zealand 'tailor made' vaccine is designed for the current situation, but the same lineage III-clone (B:4:P1.7-2,4) is the predominant group B meningococcus causing disease in several industrialised countries (17). From a global perspective, however, a more sustainable solution might be found in vaccine formulations using protein antigens with conserved epitopes, which induce functional immune responses that cross-react with the majority of the circulating group B strains (6).