Gabrielle Gaultier PhD Biotechnology Candidate Lakehead University Supervisor Dr Marina Ulanova Northern Health Research Conference 2017 1 Faculty Presenter Disclosure Slide 2 ID: 795977
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Slide1
B-cell responses to 13-valent pneumococcal conjugate vaccine in patients with severe chronic kidney disease
Gabrielle Gaultier, PhD Biotechnology Candidate Lakehead University Supervisor: Dr. Marina Ulanova Northern Health Research Conference 2017
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Slide2Faculty/ Presenter Disclosure Slide
2
Gabrielle Gaultier
Relationships with commercial interests: NONE
Potential for conflict(s) of interest: NONE
Slide3Pneumovax
(PPV23)Prevnar13 (PCV13)
Unconjugated pneumococcal polysaccharide vaccine
Pneumococcal polysaccharide-protein conjugated vaccine
(Diphtheria CRM197 protein)
23 serotypes
(1,2,3,4,5,6B,7F,8,9N,9V,10A,11A,12F,14,15B,17F,18C,19A,19F,20,22F,23F,33F)13 serotypes (3,4,5,6A,6B,7F,9V,14,18C,19A,19F and 23F)T cell independent responseT cell dependent response
Pneumovax and Prevnar13
In
Canada for all adults at risk for invasive pneumococcal disease including CKD
patients, 1 dose of Pneumovax is recommended Prevnar13 is recommended for children and is part of the routine infant immunization schedulePrevnar13 is approved for adults, only recommended for specific groups (ex- HIV positive adults)
http://www.phac-aspc.gc.ca/publicat/cig-gci/p04-pneu-eng.php
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Slide4Problems with Pneumovax
Katz, L. A., et al. (1980),
Nikoskelainen
,
Jukka
, et al. (1985), Rytel, Michael W., et al. (1986)Responsiveness to vaccination in patients with CKD can be diminishedPneumovax, is less effective in CKD patients than in healthy adultsLower post-vaccination antibody levels, which rapidly decline within 6 months of vaccinationClutterbuck E. A. et al. (2012)Immunization with Pneumovax in elderly, decrease in memory B-cell frequency Memory B-cell responses to subsequent immunization with PCV7, after Pneumovax were attenuated
Antibody hyporesponsiveness
can be due to the depletion of the peripheral memory B-cell pool
http://
www.sesml.org.au/latest-news/pneumovax-23-pre-filled-syringe-presentation-20-october-20154
Slide5Research Question
Does previous immunization with PPV23 affect the production of memory B cells after immunization with PCV13 in adult patients with CKD?Objectives Compare numbers of circulating memory B cells
between PPV23 naïve and those previously immunized with PPV23 > 1 year ago.
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Slide6Methods
Groups (n=30 per group)
1. CKD
& PPV23 naïve
2. CKD
&
previously immunized with PPV23 > 1 year Flow CytometryExperiment Outline
Identification of 4 major B cell subpopulations by using flurochrome labeled monoclonal antibodies
(4)
Channel
Measurement
Forward-scattered
light (FSC)
Cell size
Side-scattered light (SSC)
Cell granularity
FL1 (FITC,
519 nm)
CD5
FL2 (PE, 578 nm)
CD19
FL3 (PerCP/ Cy 5.5, 695
nm)
CD27
FL4 (APC
,
785
nm)
IgM
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Slide7Results Addressing Objective:
Compare numbers of circulating B memory cells between PPV23 naïve and those previously immunized with PPV23 > 1 year ago. 7
Group
N
Age
Sex
PPV23 naïve 32Mean= 64 Range: 33-88M= 19 F=
13
Immunized with PPV23 > 1 year ago
24
Mean= 61Range: 33-89M= 11F= 13
Statistical analysis was performed with
GraphPad
Prism using the Mann-Whitney U test, no significant differences found.
Slide8Type of B cell
Description
Naïve
(CD19
+
CD27
-IgM+)B cell that has never encountered an antigenIgM Memory (CD19+CD27+IgM+)Short lived B cell resulting from a T-independent response
Class Switched (CD19+
CD27-IgM-)
Activated
B cell, naïve B cell that has recently encountered an antigenClass Switched Memory (CD19+CD27+IgM-
)
Long lived B cell resulting from a T-dependent response, responds
rapidly upon re-exposure to antigen
Proportions of B cell Subpopulations
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Slide99
Absolute Numbers of B cell SubpopulationsStatistical analysis was performed with
GraphPad
Prism using the Mann-Whitney U test, no significant differences found.
Slide1010
Type of B cell
Description
B-1a (CD19
+
CD5
+)Responsible for secretion of IgM antibodiesB-1b (CD19+CD5-)Responsible for secretion of IgM, IgA and IgG antibodies after antigen specific stimulationCD19+ CD5
- cells have an important role in the IgG
antibody response to pneumococcal capsular polysaccharides (Moens L. et al.
2015). Statistical analysis was performed with GraphPad Prism using the Mann-Whitney U test, no significant differences found.
CD19+ CD5+/- B cells
Slide11Conclusions
In adult CKD patients immunized with PCV13, there is no difference in B cell subpopulations or total B cell numbers between those who received PPV23 over one year ago and pneumococcal vaccine naïve participants.
These
data suggest that
previous immunization with PPV23 should
not affect the abilities of
adult CKD patients to respond to immunization with PCV13.The groups are uneven because of lack of patients previously immunized with PPV23. Although PPV23 is the standard of care for CKD patients, only 45/127 enrolled in the study have been previously immunized. 11
Slide12Current NACI recommendations for immunization of adults against pneumococcal
infections12NACI October 2016
Slide13Acknowledgements
Dr. Marina UlanovaDr. William McCreadyDr. Eli NixAngele Desbiens-ForgetClinical trials nurses and Hemodialysis nurses13
Funding