Safety and immunogenicity of New Zealand strain meningococcal serogroup B OMV vaccine in healthy adults: Beginning of epidemic control

Abstract

As the first step towards control of a strain specific epidemic of meningococcal disease in New Zealand (NZ), this study, an observer-blind, randomised controlled trial in 75 healthy adults, evaluated safety and immunogenicity of two different dosages of a meningococcal group B vaccine administered in a three dose regime. The “tailor-made” outer membrane vesicle (OMV) vaccine (candidate vaccine) developed using a New Zealand meningococcal group B strain (B:4:P1.7b,4) was well tolerated with no vaccine related serious adverse events. Similar local and systemic reactions were observed in those receiving the New Zealand candidate vaccine and the control parent Norwegian vaccine (MenBvac™). A four-fold rise in serum bactericidal antibodies (SBAb) against the vaccine strain 4–6 weeks after the third vaccination was achieved in 100% of New Zealand candidate vaccine 2519 μg participants and in 87% of 50 μg participants. The safety and immunogenicity profile observed in this study of healthy adults enabled studies in children to be initiated using 25 μg dosage.

Introduction

In 2002, New Zealand (NZ) entered its 12th year of a widespread epidemic of group B meningococcal disease dominated by a clone of strains with a single Por A subtype which is estimated to account for approximately 85% of reported cases [1], [2]. The incidence of reported cases of meningococcal disease in 2002 was 14.9 per 100,000 [2]. More than 80% of cases occur in those under 20 years of age. The greatest risk is in less than one year old at an age-specific rate of 153.7 per 100,000. There was no indication that this epidemic was abating [2], [3].

Group B outer membrane vesicle (OMV) vaccines produced in Norway and Cuba have been assessed in efficacy trials and have been found to be effective in teenagers [4], [5]. The large scale use of the group B OMV vaccines, mostly in Latin America, has increased the possibility of evaluating vaccine effectiveness in ways other than a randomised trial [6]. The persistence of the epidemic and of the subtype in New Zealand, the increasing confidence that serum bactericidal antibodies (SBAb), as measured by the serum bactericidal assay (SBA), may provide an indication of protection from invasive meningococcal disease and a demonstrated robust serologic response against the homologous strain (vaccine strain specific) in infants [7] enabled a strategy of developing a strain specific “tailor-made” vaccine followed by clinical trials to be designed [8]. This was supported by the United Kingdom approach to meningococcal group C disease control where vaccines were licensed based on a serological correlate accompanied by immunogenicity and safety data [9]. While the use of the SBAb level achieved as a correlate for meningococcal vaccine efficacy is best shown by group C polysaccharide vaccine studies [10], [11], [12], SBAb has also become the primary indicator used to assess protective immunity induced by serogroup B meningococcal vaccine candidates [7], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22].

New Zealand strain vaccine production is similar to that of the parent vaccine MenBvac™ [23], with a strain change; thus establishing a similarity between the vaccine both at the developmental level and in clinical trials. This will enable linkage to the large database of safety data available for the parent vaccine.

New Zealand's approach, through a consortium of the Ministry of Health, Chiron Vaccines and a research team lead from The University of Auckland, is to conduct safety and immunogenicity trials in adults, school students, toddlers and infants. It is assumed these studies will lead to eventual vaccine licensure and the ability to offer the vaccine to all under 20-year-old in New Zealand. The aim is to achieve rapid control of the epidemic and reduce the incidence of invasive meningococcal group B disease particularly in younger children who carry the burden of disease.

This is the first use of this vaccine in humans although the similarity to the Norwegian parent vaccine MenBvac™ allowed a phase I/II trial. High immunogenicity with induction of bactericidal antibodies against the B:4:P1.7b,4 meningococcal strains from NZ was found in mice, and no unexpected toxicity or adverse events were observed [24]. This phase I/II study in healthy adults is the first in a series of studies to establish safety and demonstrate immunogenicity of the NZ candidate vaccine developed and produced at the Norwegian Institute of Public Health in collaboration with Chiron Vaccines. This will enable further studies in children. Two dosages were used (25 and 50 μg), to assist with defining an appropriate dose to be used in further studies. The parent Norwegian vaccine MenBvac™ (25 μg) was the comparator.