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).
[Show abstract][Hide abstract] ABSTRACT: An outer membrane vesicle meningococcal vaccine (MeNZB), was developed for the New Zealand epidemic strain of Neisseria meningitidis B:4:P1.7-2,4.
A phase II, randomized, observer blind, controlled study evaluating the safety, reactogenicity, and immunogenicity of MeNZB administered with routine New Zealand immunizations at 6 weeks, 3 months, and 5 months of age (n = 375). Group 1 (n = 250) received 25 mug MeNZB and routine immunizations with a fourth MeNZB dose given at 10 months (n = 51). Group 2 (n = 125) received routine immunizations only. Sero-response was a > or =4-fold rise in vaccine strain serum bactericidal antibody titer compared with baseline or a titer of at least 1:8 for baselines <1:4. Reactogenicity was monitored for 7 days after vaccination.
Sero-response in Group 1 was achieved in 53% (95% Confidence interval [CI]: 46-59, n = 239) and 69% (95% CI: 54-80, n = 45) with geometric mean antibody titers of 9 (95% CI: 7-10) and 22 (95% CI: 12-39) after the third and fourth doses, respectively. No negative interference by MeNZB on routine immunizations was detected. There were no serious adverse events judged to be vaccine related.
In this group of New Zealand infants, 4 MeNZB doses were required to demonstrate titers comparable with those achieved after 3 doses in older children. MeNZB was safe when used concomitantly with routine New Zealand immunizations to 5 months of age.
[Show abstract][Hide abstract] ABSTRACT: Neisseria meningitidis remains an important cause of severe sepsis and meningitis worldwide. The bacterium is only found in human hosts, and so must continually coexist with the immune system. Consequently, N meningitidis uses multiple mechanisms to avoid being killed by antimicrobial proteins, phagocytes, and, crucially, the complement system. Much remains to be learnt about the strategies N meningitidis employs to evade aspects of immune killing, including mimicry of host molecules by bacterial structures such as capsule and lipopolysaccharide, which poses substantial problems for vaccine design. To date, available vaccines only protect individuals against subsets of meningococcal strains. However, two promising vaccines are currently being assessed in clinical trials and appear to offer good prospects for an effective means of protecting individuals against endemic serogroup B disease, which has proven to be a major challenge in vaccine research.
[Show abstract][Hide abstract] ABSTRACT: Neisseria meningitidis causes significant disease in the form of severe sepsis syndrome or meningococcal meningitis. Owing to the susceptibility of the immune system in early life, the risk of disease after infection is significantly higher in infants. Thus far, vaccines targeted against meningococcal serogroups have struggled to provide lasting protection in young children. Even conjugate vaccines that are now routinely used in the immunization of infants require multiple dosing and the duration of protection has been shown to wane over time and require repeated booster doses. After briefly summarizing the current epidemiology according to age and serogroup, this article will consider the reasons for poor immunogenicity of vaccines in infants and will discuss the relative efficacy of the different vaccine types in this age group. It will then go on to consider strategies for optimizing the protection of infants against meningococcal disease.
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