Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant: a randomized, controlled trial

Ole S Søgaard; Nicolai Lohse; Zitta B Harboe; Rasmus Offersen; Anne R Bukh; Heather L Davis; Henrik C Schønheyder; Lars Østergaard

doi:10.1086/653112

Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant: a randomized, controlled trial

Ole S Søgaard, Nicolai Lohse, Zitta B Harboe, Rasmus Offersen, Anne R Bukh, Heather L Davis, Henrik C Schønheyder, Lars Østergaard

104 Citations (Scopus)

Abstract

BACKGROUND: Persons infected with human immunodeficiency virus (HIV) are often hyporesponsive to immunization, including pneumococcal vaccines. We hypothesized that adding CPG 7909, a toll-like receptor 9 (TLR9) agonist and vaccine adjuvant, to 7-valent pneumococcal conjugate vaccine (7vPnC) would increase its immunogenicity in HIV-infected adults.

METHODS: We performed a double-blind, placebo-controlled, phase 1b/2a trial randomizing HIV-positive patients to receive double doses of 7vPnC (Prevnar) at 0 and 3 months and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPV-23; Pneumo Novum) at 9 months, with experimental patients receiving 1 mg of CPG 7909 added to each of their 3 vaccine doses; control patients had phosphate-buffered saline added instead. Immunogenicity and safety were evaluated for up to 10 months. The primary end point was the proportion of vaccine high responders at 9 months, defined as a 2-fold increase in IgG levels to > or = 1 microg/mL for at least 5 of 7 of the 7vPnC serotypes.

RESULTS: Ninety-seven participants were included in the study. The proportion of vaccine high responders was higher in the experimental group (n = 48) than among controls (n = 49; 48.8% vs 25.0%; P = .02) at 9 months. Greater proportions of high responders were also observed at 3 (51.1% vs 39.6%; P = .26), 4 (77.3% vs 56.3%; P = .03), and 10 months (87.8% vs 51.1%; P < .001). Mild systemic and injection site reactions to 7vPnC were more common in the experimental group than the control group (100% vs 81.3%; P = .002). CPG 7909 did not increase non-7vPnC IgG levels after PPV-23 immunization. No adverse effects on CD4(+) cell count or organ functions occurred in either group.

CONCLUSIONS: The addition of a TLR9 agonist to 7vPnC significantly enhanced the proportion of vaccine high responders.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00562939 .

Original language	English
Journal	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Volume	51
Issue number	1
Pages (from-to)	42-50
Number of pages	9
ISSN	1058-4838
DOIs	https://doi.org/10.1086/653112
Publication status	Published - 1 Jul 2010
Externally published	Yes

Keywords

AIDS-Related Opportunistic Infections/prevention & control
Adjuvants, Immunologic/pharmacology
Adult
Antiretroviral Therapy, Highly Active
CD4 Lymphocyte Count
Double-Blind Method
Female
HIV Infections/drug therapy
Humans
Immunoglobulin G/blood
Intention to Treat Analysis
Male
Middle Aged
Pneumococcal Vaccines/adverse effects
Pneumonia, Pneumococcal/prevention & control
RNA, Viral
Toll-Like Receptor 9/agonists
Vaccines, Conjugate

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10.1086/653112

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Søgaard, O. S., Lohse, N., Harboe, Z. B., Offersen, R., Bukh, A. R., Davis, H. L., Schønheyder, H. C., & Østergaard, L. (2010). Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant: a randomized, controlled trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 51(1), 42-50. https://doi.org/10.1086/653112

Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant: a randomized, controlled trial. / Søgaard, Ole S; Lohse, Nicolai ; Harboe, Zitta B et al.
In: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, Vol. 51, No. 1, 01.07.2010, p. 42-50.

Research output: Contribution to journal › Journal article › Research › peer-review

Søgaard, OS, Lohse, N , Harboe, ZB, Offersen, R, Bukh, AR, Davis, HL, Schønheyder, HC & Østergaard, L 2010, 'Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant: a randomized, controlled trial', Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, vol. 51, no. 1, pp. 42-50. https://doi.org/10.1086/653112

Søgaard OS, Lohse N , Harboe ZB, Offersen R, Bukh AR, Davis HL et al. Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant: a randomized, controlled trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2010 Jul 1;51(1):42-50. doi: 10.1086/653112

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title = "Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant: a randomized, controlled trial",

abstract = "BACKGROUND: Persons infected with human immunodeficiency virus (HIV) are often hyporesponsive to immunization, including pneumococcal vaccines. We hypothesized that adding CPG 7909, a toll-like receptor 9 (TLR9) agonist and vaccine adjuvant, to 7-valent pneumococcal conjugate vaccine (7vPnC) would increase its immunogenicity in HIV-infected adults.METHODS: We performed a double-blind, placebo-controlled, phase 1b/2a trial randomizing HIV-positive patients to receive double doses of 7vPnC (Prevnar) at 0 and 3 months and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPV-23; Pneumo Novum) at 9 months, with experimental patients receiving 1 mg of CPG 7909 added to each of their 3 vaccine doses; control patients had phosphate-buffered saline added instead. Immunogenicity and safety were evaluated for up to 10 months. The primary end point was the proportion of vaccine high responders at 9 months, defined as a 2-fold increase in IgG levels to > or = 1 microg/mL for at least 5 of 7 of the 7vPnC serotypes.RESULTS: Ninety-seven participants were included in the study. The proportion of vaccine high responders was higher in the experimental group (n = 48) than among controls (n = 49; 48.8\% vs 25.0\%; P = .02) at 9 months. Greater proportions of high responders were also observed at 3 (51.1\% vs 39.6\%; P = .26), 4 (77.3\% vs 56.3\%; P = .03), and 10 months (87.8\% vs 51.1\%; P < .001). Mild systemic and injection site reactions to 7vPnC were more common in the experimental group than the control group (100\% vs 81.3\%; P = .002). CPG 7909 did not increase non-7vPnC IgG levels after PPV-23 immunization. No adverse effects on CD4(+) cell count or organ functions occurred in either group.CONCLUSIONS: The addition of a TLR9 agonist to 7vPnC significantly enhanced the proportion of vaccine high responders.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00562939 .",

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author = "S{\o}gaard, \{Ole S\} and Nicolai Lohse and Harboe, \{Zitta B\} and Rasmus Offersen and Bukh, \{Anne R\} and Davis, \{Heather L\} and Sch{\o}nheyder, \{Henrik C\} and Lars {\O}stergaard",

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doi = "10.1086/653112",

language = "English",

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journal = "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America",

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TY - JOUR

T1 - Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant

T2 - a randomized, controlled trial

AU - Søgaard, Ole S

AU - Lohse, Nicolai

AU - Harboe, Zitta B

AU - Offersen, Rasmus

AU - Bukh, Anne R

AU - Davis, Heather L

AU - Schønheyder, Henrik C

AU - Østergaard, Lars

PY - 2010/7/1

Y1 - 2010/7/1

N2 - BACKGROUND: Persons infected with human immunodeficiency virus (HIV) are often hyporesponsive to immunization, including pneumococcal vaccines. We hypothesized that adding CPG 7909, a toll-like receptor 9 (TLR9) agonist and vaccine adjuvant, to 7-valent pneumococcal conjugate vaccine (7vPnC) would increase its immunogenicity in HIV-infected adults.METHODS: We performed a double-blind, placebo-controlled, phase 1b/2a trial randomizing HIV-positive patients to receive double doses of 7vPnC (Prevnar) at 0 and 3 months and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPV-23; Pneumo Novum) at 9 months, with experimental patients receiving 1 mg of CPG 7909 added to each of their 3 vaccine doses; control patients had phosphate-buffered saline added instead. Immunogenicity and safety were evaluated for up to 10 months. The primary end point was the proportion of vaccine high responders at 9 months, defined as a 2-fold increase in IgG levels to > or = 1 microg/mL for at least 5 of 7 of the 7vPnC serotypes.RESULTS: Ninety-seven participants were included in the study. The proportion of vaccine high responders was higher in the experimental group (n = 48) than among controls (n = 49; 48.8% vs 25.0%; P = .02) at 9 months. Greater proportions of high responders were also observed at 3 (51.1% vs 39.6%; P = .26), 4 (77.3% vs 56.3%; P = .03), and 10 months (87.8% vs 51.1%; P < .001). Mild systemic and injection site reactions to 7vPnC were more common in the experimental group than the control group (100% vs 81.3%; P = .002). CPG 7909 did not increase non-7vPnC IgG levels after PPV-23 immunization. No adverse effects on CD4(+) cell count or organ functions occurred in either group.CONCLUSIONS: The addition of a TLR9 agonist to 7vPnC significantly enhanced the proportion of vaccine high responders.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00562939 .

AB - BACKGROUND: Persons infected with human immunodeficiency virus (HIV) are often hyporesponsive to immunization, including pneumococcal vaccines. We hypothesized that adding CPG 7909, a toll-like receptor 9 (TLR9) agonist and vaccine adjuvant, to 7-valent pneumococcal conjugate vaccine (7vPnC) would increase its immunogenicity in HIV-infected adults.METHODS: We performed a double-blind, placebo-controlled, phase 1b/2a trial randomizing HIV-positive patients to receive double doses of 7vPnC (Prevnar) at 0 and 3 months and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPV-23; Pneumo Novum) at 9 months, with experimental patients receiving 1 mg of CPG 7909 added to each of their 3 vaccine doses; control patients had phosphate-buffered saline added instead. Immunogenicity and safety were evaluated for up to 10 months. The primary end point was the proportion of vaccine high responders at 9 months, defined as a 2-fold increase in IgG levels to > or = 1 microg/mL for at least 5 of 7 of the 7vPnC serotypes.RESULTS: Ninety-seven participants were included in the study. The proportion of vaccine high responders was higher in the experimental group (n = 48) than among controls (n = 49; 48.8% vs 25.0%; P = .02) at 9 months. Greater proportions of high responders were also observed at 3 (51.1% vs 39.6%; P = .26), 4 (77.3% vs 56.3%; P = .03), and 10 months (87.8% vs 51.1%; P < .001). Mild systemic and injection site reactions to 7vPnC were more common in the experimental group than the control group (100% vs 81.3%; P = .002). CPG 7909 did not increase non-7vPnC IgG levels after PPV-23 immunization. No adverse effects on CD4(+) cell count or organ functions occurred in either group.CONCLUSIONS: The addition of a TLR9 agonist to 7vPnC significantly enhanced the proportion of vaccine high responders.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00562939 .

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KW - Adjuvants, Immunologic/pharmacology

KW - Adult

KW - Antiretroviral Therapy, Highly Active

KW - CD4 Lymphocyte Count

KW - Double-Blind Method

KW - Female

KW - HIV Infections/drug therapy

KW - Humans

KW - Immunoglobulin G/blood

KW - Intention to Treat Analysis

KW - Male

KW - Middle Aged

KW - Pneumococcal Vaccines/adverse effects

KW - Pneumonia, Pneumococcal/prevention & control

KW - RNA, Viral

KW - Toll-Like Receptor 9/agonists

KW - Vaccines, Conjugate

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DO - 10.1086/653112

M3 - Journal article

C2 - 20504165

SN - 1058-4838

VL - 51

SP - 42

EP - 50

JO - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

IS - 1

ER -

Improving the immunogenicity of pneumococcal conjugate vaccine in HIV-infected adults with a toll-like receptor 9 agonist adjuvant: a randomized, controlled trial

Abstract

Keywords

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