Phase II meningococcal B vesicle vaccine trial in New Zealand infants
ABSTRACT A tailor-made serogroup B outer membrane vesicle vaccine was evaluated in the context of a serogroup B meningococcal epidemic dominated by Neisseria meningitidis strain B:4:P1.7b,4.
To determine the safety, reactogenicity and immunogenicity in infants aged 6-8 months of a meningococcal B vaccine developed against the New Zealand epidemic strain.
Observer-blind, randomised, controlled trial conducted in 296 healthy infants in Auckland, New Zealand.
Infants were randomised 4:1 to receive three doses of New Zealand candidate vaccine (epidemic strain NZ98/254, B:4:P1.7b,4) or meningococcal C conjugate vaccine at 6-weekly intervals.
Immune response was determined by human complement mediated serum bactericidal assay. Sero-response was a fourfold or greater rise in titre compared to baseline, with baseline titres <4 required to increase to >or=8. Blood samples were taken before vaccination, 6 weeks after dose two, and 4 weeks after dose three. Local and systemic reactions were recorded for 7 days following vaccination.
Sero-response to the candidate vaccine strain, NZ98/254, was demonstrated in 74% of vaccinees (95% CI: 68% to 80% intention-to-treat; 67% to 79% per protocol) after three doses of New Zealand candidate vaccine. No meningococcal C conjugate vaccine recipients were sero-responders to NZ98/254 after three doses. Both vaccines were well tolerated with no vaccine related serious adverse events.
Our data indicate that the New Zealand candidate vaccine administered in three doses to this group of 6-8-month-old infants was safe and immunogenic against the candidate vaccine strain NZ98/254 (Neisseria meningitidis B:4:P1.7b,4).
SourceAvailable from: Johan Holst[Show abstract] [Hide abstract]
ABSTRACT: The utility of wild-type outer membrane vesicle (wtOMV) vaccines against serogroup B (MenB) meningococcal disease has been explored since the 1970s. Public health interventions in Cuba, Norway and New Zealand have demonstrated that these protein-based vaccines can prevent MenB disease. Data from large clinical studies and retrospective statistical analyses in New Zealand give effectiveness estimates of at least 70%. A consistent pattern of moderately reactogenic and safe vaccines has been seen with the use of approximately 60 million doses of three different wtOMV vaccine formulations. The key limitation of conventional wtOMV vaccines is their lack of broad protective activity against the large diversity of MenB strains circulating globally. The public health intervention in New Zealand (between 2004-2008) when MeNZB was used to control a clonal MenB epidemic, provided a number of new insights regarding international and public-private collaboration, vaccine safety surveillance, vaccine effectiveness estimates and communication to the public. The experience with wtOMV vaccines also provide important information for the next generation of MenB vaccines designed to give more comprehensive protection against multiple strains.Human Vaccines & Immunotherapeutics 03/2013; 9(6). DOI:10.4161/hv.24129 · 3.64 Impact Factor
Article: Vaccines for low-income countries.[Show abstract] [Hide abstract]
ABSTRACT: Low-income countries typically lag behind industrialised nations, where the introduction of new vaccines is commonly tailored to the pressures of the commercial market. Happily in recent years this paradigm has started to change with the introduction of a univalent meningococcal A conjugate vaccine that is specifically targeted for the prevention of epidemic meningitis in Africa. The declaration of the 2010s as a New Decade of Vaccines, together with Millennium Development Goals 4 and 5, provide a strong mandate for a new approach to the development of vaccines for low-income countries, so that there has never been a more exciting time to work in this field. This review considers the opportunities and challenges of developing these new vaccines in the context of innovations in vaccinology, the need to induce protective immunity in the populations at risk and the requirement for strong partnership between the countries that will use these vaccines and different elements of the vaccine industry.Seminars in Immunology 06/2013; DOI:10.1016/j.smim.2013.05.004 · 6.12 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The first meningococcal vaccine with the potential to provide broad coverage against serogroup B disease has recently been approved for use in Europe. This vaccine, multi-component serogroup B vaccine (4CMenB), contains recombinant proteins and outer membrane vesicles, and has been extensively studied in clinical trials involving over 7500 adults, children and infants. As well as demonstrating immunogenicity against a range of serogroup B meningococcal strains, these trials have also demonstrated relatively high rates of fever following infant immunization. This article will summarize the vaccine composition, clinical trials and suggested schedules of this vaccine, with specific attention to immunogenicity, reactogenicity, safety, potential coverage and optimal implementation of this vaccine.Expert Review of Vaccines 08/2013; 12(8):837-58. DOI:10.1586/14760584.2013.814862 · 4.22 Impact Factor