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Investigation of immunological effect of candidate meningococcal B vaccines in adults.

  • Researchers:
    Dr Ray Borrow, Prof David Goldblatt, Prof Liz Miller
  • Start Date:
    01 January 2000
  • Category:
  • Location:
    HPA Centre for Infections, London, UK
Investigation of immunological effect of candidate meningococcal B vaccines in adults.

Development of vaccines for the prevention of meningococcal B disease is a high public health priority and requires intensive research efforts, in particular to help elucidate the immunological correlates of protection. Since two serosubtype specific vaccines exist which are protective in teenagers and older age groups, the immune responses induced by these two vaccines in adults to heterologous and homologous serosubtypes will be investigated using a battery of immunological assays, and compared with those to other B vaccines designed to provide immunity to a wider range of B serosubtypes. Phase II trials will be conducted with available meningococcal B vaccines. This includes the Norwegian OMV vaccine with 30 adults subjects each given 3 doses 6 weeks apart and sera taken before and after each dose. Also the New Zealand OMV vaccine in which 50 university students will be enrolled in either a 4 dose schedule at 0, 6, 12 and 60 weeks or a 3 dose schedule of 0, 12 and 60 weeks. The following functional assays and ELISAs will be developed and applied to trial sera including: serum bactericidal antibody (SBA) assays against isogenic and prevalent wild type target strains with investigation of the effect of different complement sources, a whole-blood assay, opsonphagocytosis and measurement of proliferative in vitro T-cell responses and cytokine profiles. ELISAs to measure both total and high avidity antibodies to OMV preparations from the candidate vaccine strains will also be developed and evaluated on trial sera. An interlaboratory comparison of the SBA assay will also be performed with New Zealand, Chiron Vaccines and the Norwegian NIPH in order to validate the SBA assay in the New Zealand laboratory. Immunoblotting will be used to investigate the array of immunogenic antigens induced by each vaccine. In conjunction with GSK the immunogenicity of a bivalent OMV vaccine on prevalent UK meningococcal group B strains will be performed using the SBA assay. Two vaccine schedules, each of three doses, will be compared, either 0, 2 and 4 months or 0, 1 and 6 months. The availability of a validated repertoire of functional and non-functional assays designed to explore fully the immune response would greatly facilitate any future work done in infants.

Results from this study have been published in scientific journals as follows:

Borrow R, Aaberge IS, Santos GF, Eudey TL, Oster P, Glennie A, Findlow J, Hoiby EA, Rosenqvist E, Balmer P, Martin D.
Interlaboratory standardization of the measurement of serum bactericidal activity by using human complement against meningococcal serogroup b, strain 44/76-SL, before and after vaccination with the Norwegian MenBvac outer membrane vesicle vaccine.
Clin Diagn Lab Immunol 2005 Aug;12(8):970-6.

Findlow J, Taylor S, Aase A, Horton R, Heyderman RS, Southern J, Andrews N, Barchha R, Harrison E, Lowe A, Boxer E, Miller E.
Comparison and correlation of neisseria meningitidis serogroup B immunologic assay results and human antibody responses following three doses of the Norwegian meningococcal outer membrane vesicle vaccine MenBvac.
Infect Immun 2006 Aug;74(8):4557-65.

Boutriau D, Poolman J, Borrow R, Findlow J, Domingo JD,, Puig-Barbera J, Baldo JM, Planelles V, Jubert A, Colomer J, Gil A, Levie K.
Immunogenicity and safety of three doses of a bivalent (B:4:p1.19,15 and B:4:p1.7-2,4) meningococcal outer membrane vesicle vaccine in healthy adolescents.
Clin Vaccine Immunol 2007 Jan;14(1):65-73. Epub 2006 Oct 25.

Findlow J, Holland A, Martin D, Oster P, Balmer P, Borrow R.
Investigation into the use of colominic acid as an absorbent to facilitate the use of complement preserved baby rabbit serum in the Neisseria meningitidis serogroup B serum bactericidal antibody assay.
Clin Vaccine Immunol 2007 Mar 7; [Epub ahead of print].

Kathleen Hawkins
Meningococcal disease
Meningococcal disease at 18 when ill now 22

The empty space on the bed where my legs once were is still emotionally painful

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