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Poor association between 13-valent pneumococcal conjugate vaccine-induced serum and mucosal antibody responses with experimental Streptococcus pneumoniae serotype 6B colonisation

Tembo, G., Mayuni, M., Kamng'ona, R., Chimgoneko, L., Chiwala, G., Sichone, S., Galafa, B., Thole, F., Mkandawire, C., Chirwa, A.E., Nsomba, E., Nkhoma, V., Ngoliwa, C., Toto, N., Makhaza, L., Muyaya, A., Kudowa, E., Henrion, Marc, Dula, D., Morton, Ben ORCID: https://orcid.org/0000-0002-6164-2854, Chikaonda, T., Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116 and Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210 (2024) 'Poor association between 13-valent pneumococcal conjugate vaccine-induced serum and mucosal antibody responses with experimental Streptococcus pneumoniae serotype 6B colonisation'. Vaccine, Vol 42, Issue 12, pp. 2975-2982.

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Abstract

Background
Pneumococcal carriage is the primary reservoir for transmission and a prerequisite for invasive pneumococcal disease. Pneumococcal Conjugate Vaccine 13 (PCV13) showed a 62% efficacy in protection against experimental Streptococcus pneumoniae serotype 6B (Spn6B) carriage in a controlled human infection model (CHIM) of healthy Malawian adults. We, therefore, measured humoral responses to experimental challenge and PCV-13 vaccination and determined the association with protection against pneumococcal carriage.

Methods
We vaccinated 204 young, healthy Malawian adults with PCV13 or placebo and nasally inoculated them with Spn6B at least four weeks post-vaccination to establish carriage. We collected peripheral blood and nasal lining fluid at baseline, 4 weeks post-vaccination (7 days pre-inoculation), 2, 7, 14 and > 1 year post-inoculation. We measured the concentration of anti-serotype 6B Capsular Polysaccharide (CPS) Immunoglobulin G (IgG) and IgA antibodies in serum and nasal lining fluid using the World Health Organization (WHO) standardised enzyme-linked immunosorbent assay (ELISA).

Results
PCV13-vaccinated adults had higher serum IgG and nasal IgG/IgA anti-Spn6B CPS-specific binding antibodies than placebo recipients 4 to 6 weeks post-vaccination, which persisted for at least a year after vaccination. Nasal challenge with Spn6B did not significantly alter serum or nasal anti-CPS IgG binding antibody titers with or without experimental pneumococcal carriage. Pre-challenge titers of PCV13-induced serum IgG and nasal IgG/IgA anti-Spn6B CPS binding antibodies did not significantly differ between those that got experimentally colonised by Spn6B compared to those that did not.

Conclusion
This study demonstrates that despite high PCV13 efficacy against experimental Spn6B carriage in young, healthy Malawian adults, robust vaccine-induced systemic and mucosal anti-Spn6B CPS binding antibodies did not directly relate to protection.

Item Type: Article
Subjects: QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies
QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 805 Vaccines. Antitoxins. Toxoids
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 200 Bacterial infections (General or not elsewhere classified)
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 210 Streptococcal infections (General or not elsewhere classified)
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW)
Digital Object Identifer (DOI): https://doi.org/10.1016/j.vaccine.2024.03.055
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 23 Apr 2024 10:10
Last Modified: 23 Apr 2024 10:11
URI: https://archive.lstmed.ac.uk/id/eprint/24392

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