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Pneumococcal IgG Antibody Responses to 23vPPV in Healthy Controls Using an Automated ELISA

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Abstract

Measurement of pre- and post-pneumococcal antibody levels after immunization with the 23-valent capsular polysaccharide pneumococcal vaccine (23vPPV) is indicative of a T-independent antibody response. The World Health Organisation ELISA is considered gold standard yet is labor-intensive and technically difficult to perform. Interpretation criteria defining an adequate response to 23vPPV remain controversial. The diagnostic Immunology Laboratory at The Royal Children’s Hospital, Melbourne (RCH), performs an in-house multi-serotype automated ELISA. The primary objective of this study was to verify RCH interpretation criteria for the laboratory’s automated ELISA. Forty pneumococcal conjugate vaccine (PCV)–naïve healthy adults aged 18 to 25 years and 22 PCV-primed healthy children aged 2 to 5 years were immunized with 23vPPV. A serum sample was collected immediately prior and 28 to 42 (± 7) days post immunization. Samples were analyzed on the Tecan Freedom Evo 200 ELISA with adequate response defined as post-immunization antibody level of 1.3 µg/mL or fourfold rise from baseline in ≥ 10/15 serotypes in adult participants and ≥ 4/8 serotypes in pediatric participants. Thirty-nine (97.5%) adults and 22 (100%) children achieved an adequate response to 23vPPV. In PCV-naïve adults, serotypes contained within the conjugate vaccines were less immunogenic, with 12 (30%) adults not achieving an adequate antibody response when only PCV serotypes were used for interpretation. Our diagnostic laboratory has verified the interpretation criteria used for an automated multi-serotype pneumococcal ELISA method. Clinical Trial Registration: ANZCTR registration number ACTRN12618000822280.

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Data Availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

References

  1. Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136:1186-1205.e78.

    Article  Google Scholar 

  2. Orange JS, Ballow M, Stiehm ER, et al. Use and interpretation of diagnostic vaccination in primary immunodeficiency: a working group report of the Basic and Clinical Immunology Interest Section of the American Academy of Allergy, Asthma & Immunology. J Allergy Clin Immunol. 2012;130:S1–24.

    Article  Google Scholar 

  3. Koskela M. Serum antibodies to pneumococcal C polysaccharide in children: response to acute pneumococcal otitis media or to vaccination. Pediatr Infect Dis J. 1987;6:519–26.

    Article  CAS  Google Scholar 

  4. Coughlin RT, White AC, Anderson CA, Carlone GM, Klein DL, Treanor J. Characterization of pneumococcal specific antibodies in healthy unvaccinated adults. Vaccine. 1998;16:1761–7.

    Article  CAS  Google Scholar 

  5. Concepcion NF, Frasch CE. Pneumococcal type 22F polysaccharide absorption improves the specificity of a pneumococcal-polysaccharide enzyme-linked immunosorbent assay. Clin Diagn Lab Immunol. 2001;8:266–72.

    Article  CAS  Google Scholar 

  6. Sorensen RU. A critical view of specific antibody deficiencies. Front Immunol. 2019;10:986.

    Article  CAS  Google Scholar 

  7. Meek B, Ekström N, Kantsø B, et al (2019) Multilaboratory comparison of pneumococcal multiplex immunoassays used in immunosurveillance of streptococcus pneumoniae across Europe. mSphere. https://doi.org/10.1128/mSphere.00455-19

  8. Hajjar J, Al-Kaabi A, Kutac C, Dunn J, Shearer WT, Orange JS. Questioning the accuracy of currently available pneumococcal antibody testing. J Allergy Clin Immunol. 2018;142:1358–60.

    Article  Google Scholar 

  9. Whaley MJ, Rose C, Martinez J, et al. Interlaboratory comparison of three multiplexed bead-based immunoassays for measuring serum antibodies to pneumococcal polysaccharides. Clin Vaccine Immunol. 2010;17:862–9.

    Article  CAS  Google Scholar 

  10. Daly TM, Pickering JW, Zhang X, Prince HE, Hill HR. Multilaboratory assessment of threshold versus fold-change algorithms for minimizing analytical variability in multiplexed pneumococcal IgG measurements. Clin Vaccine Immunol. 2014;21:982–8.

    Article  Google Scholar 

  11. Zhang X, Simmerman K, Yen-Lieberman B, Daly TM. Impact of analytical variability on clinical interpretation of multiplex pneumococcal serology assays. Clin Vaccine Immunol. 2013;20:957–61.

    Article  CAS  Google Scholar 

  12. Sorensen RU, Leiva LE, Javier FC, Sacerdote DM, Bradford N, Butler B, Giangrosso PA, Moore C. Influence of age on the response to Streptococcus pneumoniae vaccine in patients with recurrent infections and normal immunoglobulin concentrations. J Allergy Clin Immunol. 1998;102:215–21.

    Article  CAS  Google Scholar 

  13. Kamchaisatian W, Wanwatsuntikul W, Sleasman J, Tangsinmankong N. Validation of current joint American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma and Immunology guidelines for antibody response to the 23-valent pneumococcal vaccine using a population of HIV-infected children. J Allergy Clin Immunol. 2006;118:1336–41.

    Article  CAS  Google Scholar 

  14. Anonymous. Pneumococcal conjugate vaccines in infants and children under 5 years of age: WHO position paper – February 2019. Wkly Epidemiol Rec. 2019;94:85–104.

    Google Scholar 

  15. Beck SC. Making sense of serotype-specific pneumococcal antibody measurements. Ann Clin Biochem. 2013;50:517–9.

    Article  Google Scholar 

  16. Go E, Ballas Z. Anti-pneumococcal antibody response in normal subjects: a meta-analysis. J Allergy Clin Immunol. 1996;98:205–15.

    Article  CAS  Google Scholar 

  17. Gary L. Horowitz, Sousan Altaie, James C. Boyd, Ferruccio Ceriotti, Uttam Garg, Paul Horn, Amadeo Pesce, Harrison E. Sine, Jack Zakowski (2010) Defining, establishing, and verifying reference intervals in the Clinical Laboratory; Approved Guideline—Third Edition.

  18. Uddin S, Borrow R, Haeney MR, Moran A, Warrington R, Balmer P, Arkwright PD. Total and serotype-specific pneumococcal antibody titres in children with normal and abnormal humoral immunity. Vaccine. 2006;24:5637–44.

    Article  CAS  Google Scholar 

  19. Park MA, Jenkins SM, Smith CY, Pyle RC, Sacco KA, Ryu E, Hagan JB, Joshi AY, Snyder MR, Abraham RS. Pneumococcal serotype-specific cut-offs based on antibody responses to pneumococcal polysaccharide vaccination in healthy adults. Vaccine. 2021;39:2850–6.

    Article  CAS  Google Scholar 

  20. H Schaballie B Bosch R Schrijvers et al 2017 Fifth percentile cutoff values for antipneumococcal polysaccharide and anti-salmonella typhi Vi IgG describe a normal polysaccharide response Front Immunol https://doi.org/10.3389/fimmu.2017.00546

  21. Hare ND, Smith BJ, Ballas ZK. Antibody response to pneumococcal vaccination as a function of preimmunization titer. J Allergy Clin Immunol. 2009;123:195–200.

    Article  CAS  Google Scholar 

  22. Park S, Nahm MH. Older adults have a low capacity to opsonize pneumococci due to low IgM Antibody response to pneumococcal vaccinations. Infect Immun. 2011;79:314–20.

    Article  CAS  Google Scholar 

  23. Chiarella SE, Jenkins SM, Park MA, Abraham RS, Joshi AY. Sex differences in antibody responses to the 23-valent pneumococcal polysaccharide vaccination. Ann Allergy Asthma Immunol. 2021;127:509–10.

    Article  CAS  Google Scholar 

  24. D LaFon Y Kim R Burton M Dransfield M Nahm 2021 Pneumococcal antibody function for immunologic evaluation: normal results in older adults, and a novel analytical model for vaccine response J ClinImmunol https://doi.org/10.1007/s10875-021-01126-z

  25. U.S. Food and Drug Administration, Centre for Biologics Evaluation and Research (2021) July 16, 2021 - Approval Letter - VAXNEUVANCE.

  26. U.S. Food and Drug Administration, Centre for Biologics Evaluation and Research (2021) June 10, 2021 Approval Letter - PREVNAR 20.

  27. Evans C, Bateman E, Steven R, et al. Measurement of typhi Vi antibodies can be used to assess adaptive immunity in patients with immunodeficiency. Clin Exp Immunol. 2018;192:292–301.

    Article  CAS  Google Scholar 

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Acknowledgements

We would like to thank Sonja Elia at RCH Immunisation Service for her support of this study.

Funding

This work was supported by The RCH Foundation.

Author information

Authors and Affiliations

  1. Immunology Laboratory, Laboratory Services, Royal Children’s Hospital, Melbourne, Australia

    Laine M. Hosking, Christine Czajko, Marilyn Clark, Sinead Flynn, Stephanie Richards & Sharon Choo

  2. Department of Allergy and Immunology, Royal Children’s Hospital, Melbourne, Australia

    Laine M. Hosking, Kirsten P. Perrett, Stephanie Richards & Sharon Choo

  3. Population Allergy Research Group & Melbourne Children’s Trial Centre, Murdoch Children’s Research Institute, Melbourne, Australia

    Kirsten P. Perrett

  4. Department of Paediatrics, The University of Melbourne, Melbourne, Australia

    Kirsten P. Perrett

Authors
  1. Laine M. Hosking
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  2. Kirsten P. Perrett
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  3. Christine Czajko
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  4. Marilyn Clark
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  5. Sinead Flynn
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  6. Stephanie Richards
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  7. Sharon Choo
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Contributions

Laine Hosking, Sharon Choo, Kirsten Perrett and Stephanie Richards contributed to study conception and design. Christine Czjako and Marilyn Clark designed the automated ELISA and Sinead Flynn performed the experiments. Laine Hosking analyzed the data. The first draft of the manuscript was written by Laine Hosking and Sharon Choo and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Laine M. Hosking.

Ethics declarations

Ethics Approval

This study was performed in line with the Australian National Statement on Ethical Conduct in Human Research. Approval was granted by the Royal Children’s Hospital Human Research Ethics Committee (protocol number 37183).

Consent to Participate

Informed consent was obtained from all individual participants or their guardians included in the study.

Consent for Publication

Not applicable, no individual data included in the manuscript.

Conflict of Interest

The authors declare no competing interests.

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Appendices

Appendix

Appendix 1. Inclusion and exclusion criteria

Inclusion Criteria

Each adult must meet all of the following criteria to be enrolled in this study:

  • Is between the ages of 18 and 25 years at the time of enrolment

  • Is capable of understanding the informed consent document and providing consent

  • Is available to attend the study follow-up

Each child must meet all of the following criteria to be enrolled in this study:

  • Is between the ages of 2 and 5 years at the time of enrolment

  • Has received Prevenar13 as per the Australian National Immunisation Program Schedule at 2-, 4-, and 6 months of age

  • Has a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant’s behalf

  • Is available to attend the study follow-up

Exclusion criteria

Participants meeting any of the following criteria will be excluded from the study:

  • Prior immunization with 23vPPV

  • Has a known hypersensitivity to any of the components of the 23vPPV vaccine

  • Has a current fever or infection

  • Is taking immunosuppressant medication, e.g. oral corticosteroids

  • Has a prior diagnosis of invasive pneumococcal infection

  • Has a pre-existing medical condition associated with increased risk of invasive pneumococcal disease

  • Is currently pregnant, or considering pregnancy during the study period

  • Is known to require a pneumococcal immunization prior to the completion of the study follow-up

  • Inability or unwillingness of participant or legally acceptable representative to give written informed consent

In addition, for adult participants, the following exclusion criteria apply:

  • Prior immunization with a pneumococcal conjugate vaccine

Appendix 2

Table 4 Concentrations of IgG antibodies to serotypes in standard preparation 007sp
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Hosking, L.M., Perrett, K.P., Czajko, C. et al. Pneumococcal IgG Antibody Responses to 23vPPV in Healthy Controls Using an Automated ELISA. J Clin Immunol 42, 760–770 (2022). https://doi.org/10.1007/s10875-022-01230-8

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  • DOI: https://doi.org/10.1007/s10875-022-01230-8

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