Safety and immunogenicity of New Zealand strain meningococcal serogroup B OMV vaccine in healthy adults: Beginning of epidemic control
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.
Section snippets
Study design
A phase I/II randomised, controlled, observer-blind study of OMV vaccines among healthy adult (18–50 years inclusive) volunteers was undertaken. Recruitment of hospital staff took place in Auckland, New Zealand.
Ethics approval from the Ministry of Health Ethics Committee (Auckland region) was obtained and 75 participants provided written informed consent before enrolment. Participants were excluded by medical history and/or physical examination if they were pregnant had a hypersensitivity to
Results
Seventy-five participants were enrolled in the study conducted between May and October 2002. The mean age of participants was 34.6 years (range 20–50 years) with 52 (69%) participants female. Seventy-three participants completed the three-dose regimen and provided four blood samples. One participant from each of the NZ candidate vaccine groups withdraw at the time of the second vaccination. These withdrawals were unrelated to the vaccine. Five participants were excluded on one occasion from
Discussion
This is the first study of the New Zealand meningococcal P1.7b, 4 vaccine in humans and the beginning of the pathway to epidemic control. The safety and immunogenicity profile observed in this study of healthy adults enabled studies in children to be initiated using the 25 μg dosage.
The results confirmed the New Zealand candidate vaccine has a reactogenicity profile similar to MenBvac™ [25]. Furthermore, there were no serious vaccine related adverse events. The incidence of local and systemic
Acknowledgements
We thank the study participants for their altruism in taking part. We also thank the research co-ordinators Sarah Douglas and Robyn Beckerleg, the study nurses, the laboratory workers at ESR Anne Glennie, Nicola Ruijne, Lisa McCallum and the study staff at Chiron Vaccines. We acknowledge the assistance of the District Health Boards. This study was funded by the New Zealand Ministry of Health and Chiron Vaccines.
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2017, VaccineCitation Excerpt :Rosenqvist et al. have shown that MenBvac® induced in adult volunteers significant SBA response against variants of the vaccine strain lacking some outer membrane proteins [8]. The Norwegian Institute of Public Health team had performed a study in adult volunteers comparing the immunogenicity of MenBvac® (P1.7,16 strain) and MeNZB® (P1.7-2,4 strain) showing that SBA titres were better against the homologous strain than with the heterologous strain [9,20]. Tappero et al. have reported that both MenBvac (P1.7,16 strain) and the Finlay Institute OMV vaccine (P1.15 strain) did not induce significant response in infants while children and adults showed SBA titres against a heterologous strain but to a lesser extent than to the vaccine homologous strain [18].