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• Assessing Immune responses to pneumococcal vaccines
  Raman Lakshman
  Published on: 22 March 2016

• Published on: 22 March 2016

  Assessing Immune responses to pneumococcal vaccines

  • Raman Lakshman, Specialist Registrar
  • Other Contributors:
    • Andrew R Gennery, Peter D Arkwright, Terrence Flood, Peter Balmer, Mario Abinun, G Spickett, Ray Borrow and Andrew J Cant

  Dear Editor

  The recent article and letter [1,2] discussing recommendations for use of heptavalent pneumococcal conjugate vaccine (Prevenar) for at risk children is timely and interesting. We concur with the authors that further immunogenicity studies are necessary in various high-risk groups to demonstrate the best protective schedule.

  Children older than 2 years with recurrent infections and normal humor...

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  Dear Editor

  The recent article and letter [1,2] discussing recommendations for use of heptavalent pneumococcal conjugate vaccine (Prevenar) for at risk children is timely and interesting. We concur with the authors that further immunogenicity studies are necessary in various high-risk groups to demonstrate the best protective schedule.

  Children older than 2 years with recurrent infections and normal humoral immunity assessed by serum immunoglobulin levels and specific antibody responses to protein antigens, but repeated poor responses (less than 4 fold rise in antibody titers) to 23 valent pneumococcal polysaccharide vaccine (Pneumovax) using standard pneumovax based ELISA [3] are labelled as ‘specific pneumococcal polysaccharide antibody’ deficiency.[4]

  We looked at the immunogenicity of the heptavalent conjugate pneumococcal vaccine (Prevnar) in 5 children aged 4-12 years with specific polysaccharide antibody deficiency by the above definition. Blood was collected before and 4 weeks after immunization with the heptavalent conjugate pneumococcal vaccine. Serum was analysed using the standard ELISA (using Pneumovax as the antigen) [4] and by the newer serotype specific antibody assay performed by the Workd Protection Agency, Manchester (http://www.vaccine.uab.edu/WHO2.pdf

  Results are shown in table 1 and 2. The standard assay showed 4-fold response in only 1 child. However 5/5 children showed 4 fold responses to at least 4 of the 7 serotypes using the serotype specific antibody assay.

  Protection is assumed at a serotype specific antibody level of 0.2 ug/ml or greater.[5] It is interesting to note that 4 out of 5 children had achieved such protective levels to 4 of more serotypes after immunisation with pneumovax as suggested by the serotype specific assay on the pre-prevenar sera.

  Clinicians may be tempted to use the more easily available standard ELISA to assess responses to the conjugate vaccine in high risk children. These findings suggest that whilst assessing such responses it is important to use the serotype specific assay to get true measure of adequacy of response.[6] The study also suggests that there may be a group of children in whom an immune response to Pneumovax is detectable only by the serotype specific assay and who may be labelled as specific antibody deficient by the standard assay.

  References

  (1) Finn A, Booy R, Sharland M, Heath P. Should the new pneumococcal vaccine be used in high-risk children? Arch Dis Child 2002; 87:18-21.

  (2) Finn A, Booy R, Sharland M, Heath P. Conflicting advice. Arch Dis Child 2003; 88:176.

  (3) Griffiths H, Lea J, Bunch C, Lee M, Chapel H. Predictors of infection in chronic lymphocytic leukaemia (CLL). Clin Exp Immunol 1992;89:374-377.

  (4) Rijkers GT, Sandesr LAM, Zegers BJM. Anti-capsular polysaccharide antibody deficiency states. Immunodeficieny 1993;5:1-21.

  (5) Luis Jódar, Jay Butler, George Carlone, et al. Serological criteria for evaluation and licensure of new pneumococcal conjugate vaccine formulations for use in infants. Vaccine 2003; in Press.

  (6) Balmer P, North J, Baxter D, Stanford E, Melegaro A, Kaczmarski EB et al. Measurement and interpretation of pneumococcal IgG levels for clinical management. Clin Exp Immun (submitted).

  Table 1 Pneumococcal antibody responses using Pneumovax antigen ELISA.
  

  Subject	Pneumo u/ml
  	Pre vaccine	4 weeks post vaccine
  1	18.1	32.6
  2	4.4	9.1
  3	11.1	28.6
  4	18.8	33.2
  5	6.8	29

  Table 2 Serotype specific responses - pre and 4 weeks post Prevnar
  

  Subject	Date of Sample	Pneumococcal serotype specific antibody titres in ug/ml
  		4	14	19F	23F	6B	18C	9V
  1	1 pre- prevnar	0.76	0.65	1.03	0.62	0.49	0.79	0.16
  	4 weeks post	4.77	87.44	2.84	16.5	21.79	1.03	4.74
  2	2 pre- prevnar	0.10	0.11	0.41	0.07	0.09	0.05	0.04
  	4 weeks post	6.42	1.76	2.88	0.47	0.22	57.24	1.05
  3	3 pre- prevnar	0.24	2.6	4.45	0.25	0.6	0.38	0.29
  	4 weeks post	5.30	6.58	6.54	3.26	2.38	2.78	7.71
  4	4 pre- prevnar	0.64	0.33	7.23	0.11	0.53	0.28	0.76
  	4 weeks post	58.82	33.94	12.39	26.6	1.24	3.83	2.95
  5	5 pre- prevnar	0.80	2.82	1.25	0.13	0.14	0.33	0.13
  	4 weeks post	44.01	119.59	19.36	48.14	0.82	106.55	3.25

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  Conflict of Interest:
  None declared.

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