Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness

Sarah Moberley, Paul V. Licciardi, Anne Balloch, Ross Andrews, Amanda J. Leach, Marie Kirkwood, Paula Binks, Edward (Kim) MULHOLLAND, Jonathan Carapetis, Mimi L K Tang, Sue Skull

    Research output: Contribution to journalArticleResearchpeer-review

    Abstract

    Background: Indigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults.

    Methods:
    Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. Individuals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration; a two-fold rise if the post vaccination antibody was >1.3 μg/ml but <4.0 μg/ml; or a post-vaccination antibody concentration >4.0 μg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N = 20) and Indigenous (N = 60) and non-Indigenous adults (N = 25) receiving their first 23vPPV dose.

    Results: All non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of individuals with an adequate response using our definition (primary endpoint), with 88% of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70% having an adequate response following a second dose of 23vPPV (14/20; p = 0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70% (−27%, 95% CI: −43% to −11%; p = 0.01) and 90% (−38%, 95% CI: −60% to −16%; p = 0.006) of serotypes with a positive response.

    Conclusion: Indigenous participants demonstrated a poorer response to a first dose 23vPPV compared to their non-Indigenous counterparts, with lower IgG following a second 23vPPV dose. These findings highlight the critical need to evaluate the efficacy of future pneumococcal vaccine programs in the Australian Indigenous populations that recommend repeated doses of 23vPPV.
    Original languageEnglish
    Pages (from-to)2908-2915
    Number of pages8
    JournalVaccine
    Volume35
    Issue number22
    Early online date20 Apr 2017
    DOIs
    Publication statusPublished - 19 May 2017

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    Pneumococcal Vaccines
    polysaccharides
    vaccines
    dosage
    serotypes
    Vaccination
    vaccination
    immune response
    Vaccines
    Immunoglobulin G
    Northern Territory
    Antibodies
    antibodies
    Population Groups
    endpoints

    Cite this

    Moberley, Sarah ; Licciardi, Paul V. ; Balloch, Anne ; Andrews, Ross ; Leach, Amanda J. ; Kirkwood, Marie ; Binks, Paula ; MULHOLLAND, Edward (Kim) ; Carapetis, Jonathan ; Tang, Mimi L K ; Skull, Sue. / Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness. In: Vaccine. 2017 ; Vol. 35, No. 22. pp. 2908-2915.
    @article{a831b3dd5be24714b046ec0b19731a2e,
    title = "Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness",
    abstract = "Background: Indigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults.Methods: Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. Individuals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration; a two-fold rise if the post vaccination antibody was >1.3 μg/ml but <4.0 μg/ml; or a post-vaccination antibody concentration >4.0 μg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N = 20) and Indigenous (N = 60) and non-Indigenous adults (N = 25) receiving their first 23vPPV dose.Results: All non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of individuals with an adequate response using our definition (primary endpoint), with 88{\%} of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70{\%} having an adequate response following a second dose of 23vPPV (14/20; p = 0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70{\%} (−27{\%}, 95{\%} CI: −43{\%} to −11{\%}; p = 0.01) and 90{\%} (−38{\%}, 95{\%} CI: −60{\%} to −16{\%}; p = 0.006) of serotypes with a positive response.Conclusion: Indigenous participants demonstrated a poorer response to a first dose 23vPPV compared to their non-Indigenous counterparts, with lower IgG following a second 23vPPV dose. These findings highlight the critical need to evaluate the efficacy of future pneumococcal vaccine programs in the Australian Indigenous populations that recommend repeated doses of 23vPPV.",
    keywords = "Adequate immune response, Hyporesponsiveness, Immunogenicity, Indigenous, Pneumococcal polysaccharide vaccine",
    author = "Sarah Moberley and Licciardi, {Paul V.} and Anne Balloch and Ross Andrews and Leach, {Amanda J.} and Marie Kirkwood and Paula Binks and MULHOLLAND, {Edward (Kim)} and Jonathan Carapetis and Tang, {Mimi L K} and Sue Skull",
    year = "2017",
    month = "5",
    day = "19",
    doi = "10.1016/j.vaccine.2017.04.040",
    language = "English",
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    pages = "2908--2915",
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    issn = "0264-410X",
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    }

    Moberley, S, Licciardi, PV, Balloch, A, Andrews, R, Leach, AJ, Kirkwood, M, Binks, P, MULHOLLAND, EK, Carapetis, J, Tang, MLK & Skull, S 2017, 'Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness', Vaccine, vol. 35, no. 22, pp. 2908-2915. https://doi.org/10.1016/j.vaccine.2017.04.040

    Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness. / Moberley, Sarah; Licciardi, Paul V.; Balloch, Anne; Andrews, Ross; Leach, Amanda J.; Kirkwood, Marie; Binks, Paula; MULHOLLAND, Edward (Kim); Carapetis, Jonathan; Tang, Mimi L K; Skull, Sue.

    In: Vaccine, Vol. 35, No. 22, 19.05.2017, p. 2908-2915.

    Research output: Contribution to journalArticleResearchpeer-review

    TY - JOUR

    T1 - Repeat pneumococcal polysaccharide vaccine in Indigenous Australian adults is associated with decreased immune responsiveness

    AU - Moberley, Sarah

    AU - Licciardi, Paul V.

    AU - Balloch, Anne

    AU - Andrews, Ross

    AU - Leach, Amanda J.

    AU - Kirkwood, Marie

    AU - Binks, Paula

    AU - MULHOLLAND, Edward (Kim)

    AU - Carapetis, Jonathan

    AU - Tang, Mimi L K

    AU - Skull, Sue

    PY - 2017/5/19

    Y1 - 2017/5/19

    N2 - Background: Indigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults.Methods: Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. Individuals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration; a two-fold rise if the post vaccination antibody was >1.3 μg/ml but <4.0 μg/ml; or a post-vaccination antibody concentration >4.0 μg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N = 20) and Indigenous (N = 60) and non-Indigenous adults (N = 25) receiving their first 23vPPV dose.Results: All non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of individuals with an adequate response using our definition (primary endpoint), with 88% of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70% having an adequate response following a second dose of 23vPPV (14/20; p = 0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70% (−27%, 95% CI: −43% to −11%; p = 0.01) and 90% (−38%, 95% CI: −60% to −16%; p = 0.006) of serotypes with a positive response.Conclusion: Indigenous participants demonstrated a poorer response to a first dose 23vPPV compared to their non-Indigenous counterparts, with lower IgG following a second 23vPPV dose. These findings highlight the critical need to evaluate the efficacy of future pneumococcal vaccine programs in the Australian Indigenous populations that recommend repeated doses of 23vPPV.

    AB - Background: Indigenous adults residing in the Northern Territory of Australia experience elevated rates of invasive pneumococcal disease despite the routine use of 23-valent pneumococcal polysaccharide vaccine (23vPPV). We hypothesised that the limited protection from 23vPPV may be due to hyporesponsiveness as a result of vaccine failure from repeated vaccination. To explore this possibility, we evaluated the immune response to a first and second dose of 23vPPV in Indigenous adults and a first dose of 23vPPV in non-Indigenous adults.Methods: Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline and at one month post-vaccination. Individuals were considered to have an adequate immune response if paired sera demonstrated either: a four-fold rise in antibody concentration; a two-fold rise if the post vaccination antibody was >1.3 μg/ml but <4.0 μg/ml; or a post-vaccination antibody concentration >4.0 μg/ml for at least half of the serotypes tested (12/23). Our per-protocol analysis included the comparison of outcomes for three groups: Indigenous adults receiving a second 23vPPV dose (N = 20) and Indigenous (N = 60) and non-Indigenous adults (N = 25) receiving their first 23vPPV dose.Results: All non-Indigenous adults receiving a first dose of 23vPPV mounted an adequate immune response (25/25). There was no significant difference in the proportion of individuals with an adequate response using our definition (primary endpoint), with 88% of Indigenous adults mounted an adequate response following first dose 23vPPV (53/60) compared to 70% having an adequate response following a second dose of 23vPPV (14/20; p = 0.05). The risk difference between Indigenous participants receiving first dose compared to non-Indigenous participants receiving first dose was significant when comparing a response threshold of at least 70% (−27%, 95% CI: −43% to −11%; p = 0.01) and 90% (−38%, 95% CI: −60% to −16%; p = 0.006) of serotypes with a positive response.Conclusion: Indigenous participants demonstrated a poorer response to a first dose 23vPPV compared to their non-Indigenous counterparts, with lower IgG following a second 23vPPV dose. These findings highlight the critical need to evaluate the efficacy of future pneumococcal vaccine programs in the Australian Indigenous populations that recommend repeated doses of 23vPPV.

    KW - Adequate immune response

    KW - Hyporesponsiveness

    KW - Immunogenicity

    KW - Indigenous

    KW - Pneumococcal polysaccharide vaccine

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    U2 - 10.1016/j.vaccine.2017.04.040

    DO - 10.1016/j.vaccine.2017.04.040

    M3 - Article

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    SP - 2908

    EP - 2915

    JO - Vaccine

    JF - Vaccine

    SN - 0264-410X

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