Clinical Trial: B Cell Response to a Primary and a Booster Course of the Novartis Meningococcal ACWY Conjugate Vaccine in Healthy Infants

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II, Single Center, Open-label, Randomized Study to Investigate Meningococcal Serogroup A, C, W-135 and Y Saccharide Specific B Cell Response to a Primary and a Booster Course of the Novartis M

Brief Summary: This study is aimed to assess whether the frequency of meningococcal serogroup A, C, W-135 and Y specific memory B Cells, measured 1 month after a primary vaccination series of Novartis MenACWY vaccine, predicts the specific serum bactericidal activity using human complement (hSBA) of (respectively) serogroup A, C, W-135 and Y at 12 months of age

Detailed Summary:
Sponsor: Novartis Vaccines

Current Primary Outcome: Summary of Memory B Cells Per 2 x 105 LOC by Serogroup A, C, W-135 and Y [ Time Frame: 1 month after primary vaccination and immediately before third dose at 12 months of age ]

The memory B cell response at one month after primary vaccinations (5 months of age) was defined as the mean number of meningococcal serogroup A, C, W-135 and Y specific memory B cells, measured in vitro by ELISpot assay per 2x100000 lymphocytes obtained from culture (LOC) of peripheral blood mononuclear cells (PBMC) circulating in blood incubated for 5.5 days in the presence of polyclonal B cell activators.

Serogroup A, C, W-135 and Y geometric mean titers (GMTs) were measured by serum bactericidal assay using human complement (hSBA) at 12 months of age (before third dose).

Correlation and linear regression coefficients were determined between memory B cells at 1 month after primary vaccinations with MenACWY-CRM (5 months of age) and hSBA titers at 12 months of age (before third dose) for the serogroups A, C, W-135 and Y.



Original Primary Outcome:

  • Whether the frequency of meningococcal serogroup A, C, W-135 and Y specific memory B Cells predicts the specific serum bactericidal activity using human complement of (respectively) serogroup A, C, W-135 and Y at 12 months of age
  • The safety and tolerability of Novartis MenACWY vaccine concomitantly with a combined diphtheria, tetanus toxoid, acellular pertussis, Haemophilus influenzae type B and inactivated polio vaccine and a heptavalent PCV.


Current Secondary Outcome:

  • Memory B Cells by Serogroup A, C, W-135 and Y [ Time Frame: 1 month after primary vaccination and immediately before third dose ]

    Memory B cell response at 1 month after primary vaccination and immediately before third dose at 12 months of age was measured as mean number of meningococcal serogroup specific memory B cells by ELISpot assay per 2x100000 LOC.

    The meningococcal serogroup A, C, W-135 and Y specific IgG concentrations immediately before third dose at 12 months of age were measured by ELISA.

  • Memory B Cells Per 2x100000 by Serogroup A,C, W-135 and Y at One Month After Primary MenACWY-CRM Vaccination and Third MenACWY-CRM Vaccination [ Time Frame: 1 month after primary vaccination and 1 month after third vaccination ]

    Memory B cell response at 1 month after MenACWY-CRM primary and booster vaccinations was measured as mean number of meningococcal serogroup specific memory B cells by ELISpot assay per 2x100000 LOC.

    hSBA GMTs for the serogroup A, C, W-135 and Y were measured one month after the third MenACWY-CRM vaccination.

    The meningococcal serogroup A, C, W-135 and Y specific IgG concentrations one month after third MenACWY-CRM vaccination were measured by ELISA.

  • Memory B Cells 1 Month After Primary Vaccination and Rise From Pre-third Dose to 1 Month After Third Dose of MenACWY-CRM Vaccination [ Time Frame: 1 month after primary and pre-third and 1 month after third vaccination ]

    Memory B cell response at 1 month after MenACWY-CRM primary and third (booster) vaccination was measured as mean number of meningococcal serogroup specific memory B cells by ELISpot assay per 2x100000 LOC.

    The serogroup A, C, W-135 and Y specific IgG concentrations at 1 month after MenACWY-CRM booster were measured by ELISA.

    hSBA GMTs were measured by hSBA assay one month after MenACWY-CRM booster vaccination.

    The rise in serogroup specific IgG, memory B cells and hSBA was calculated by pre/post third dose geometric mean ratios, calculated by the difference in the log10 of the concentrations/titers measured at 13 months to the log10 of the concentrations at 12 months: i.e. rise = log10(x) at 13 months minus log10(x)at 12 months where x is the serogroup specific IgG or memory B cell concentrations or SBA titers.

  • Memory B Cells 1 Month After Primary Vaccination and 1 Week After Third Vaccination by Serogroup A, C, W-135 and Y [ Time Frame: One month after primary vaccination and 1 week after third vaccination ]

    Memory B cell response at 1 month after primary vaccination and at 1 week after third vaccination was measured as mean number of meningococcal serogroup specific memory B cells by ELISpot assay per 2x100000 LOC.

    Plasma B cell response at 1 week after vaccination was measured as the mean number of cells secreting antibodies specific for meningococcal serogroup A, C, W-135 and Y, measured by ELISpot assay, per 2x100000 PBMC.

    Serogroup A, C, W-135 and Y specific IgG were measured by ELISA and hSBA GMTs were measured at 1 week after third vaccination.

  • CRM197 Specific Memory B Cells 1 Month After Primary Vaccination and at 12 Months of Age and One Month After MenACWY-CRM Third Vaccination [ Time Frame: 5 months (B cells), 12 months and 13 months (B cells and IgG) of age ]

    CRM197 specific memory B cell response at each time point was measured as mean number of CRM197 specific memory B cells by ELISpot assay per 2x100000 LOC.

    CRM197 specific IgG concentration was measured by ELISA at 12 months of age and one month after MenACWY-CRM booster vaccination.

  • Increase in Serogroup A, C, W-135 and Y Specific Memory B Cells Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone [ Time Frame: Before and one month after booster vaccination ]
    Memory B cell response before and one month after MenACWY-CRM booster vaccination at 12 months of age was measured as mean number of meningococcal serogroup A, C, W-135 and Y specific memory B cells by ELISpot assay per 2x100000 LOC.
  • Increase in Serogroup A, C, W-135 and Y Specific hSBA Titers Before and 1 Month After MenACWY-CRM Booster Vaccination at 12 Months of Age Administered Concomitantly With Pneumococcal Conjugate Vaccine or Alone [ Time Frame: Before and one month after booster vaccination ]
    hSBA GMTs were measured before and one month after MenACWY-CRM booster vaccination at 12 months of age.
  • Serogroups A, C, W-135 and Y Specific Memory B Cell Response in Children Lacking a hSBA Titer of ≥1:8 One Mo

    Original Secondary Outcome:

    • Whether the frequency of meningococcal serogroup A, C, W-135 and Y specific memory B Cells predicts the concentration of (respectively) serogroup A, C, W-135 and Y specific IgG and memory B-cells at 12 months of age
    • Whether the frequency of meningococcal serogroup A,C,W-135 and Y specific memory B Cells predicts serogroup A,C,W-135 and Y specific memory B-cells and IgG concentrations and hSBA titers 1 month after a booster of MenACWY administered at 12 months of age
    • Whether the frequency of meningococcal serogroup A,C,W-135,Y specific B Cells predicts the rise from prebooster levels in serogroup A,C,W-135,Y specific IgG and B-cell conc. and hSBA titers 1 month after a booster of MenACWY admin. at 12 months of age
    • Whether the frequency of meningococcal serogroup A,C,W135,Y specific B Cells predicts the conc. of serogroup A,C,W135,Y specific plasma cells and B-cells and specific IgG and hSBA titers in the week after a booster of MenACWY admin. at 12months of age
    • Whether the frequency of CRM197 specific memory B Cells predicts the concentration of CRM197 specific IgG and memory B Cells at 12 months of age and one month following a booster dose of MenACWY administered at 12 months of age


    Information By: Novartis

    Dates:
    Date Received: June 19, 2007
    Date Started: July 2007
    Date Completion:
    Last Updated: September 18, 2014
    Last Verified: September 2014