Pneumococcal capsular polysaccharide vaccine-mediated protection against serotype 3 Streptococcus pneumoniae in immunodeficient mice

Haijun Tian, Avi Groner, Marianne Boes, Liise-anne Pirofski

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Pneumococcal capsular polysaccharide (PPS) vaccines are less immunogenic in immunocompromised than immunocompetent individuals. However, neither the efficacy of PPS vaccines in immunocompromised individuals nor the host cellular subsets required for vaccine efficacy against pneumococcal disease have been directly investigated. In this study, we vaccinated CD4-deicient (CD4 -/-), CD8-deficient (CB8-/-), and secretory immunoglobulin M-deficient (sIgM-/-) mice and wild-type C57BL/6 (Wt) mice with a conjugate of PPS of serotype 3 and tetanus toxoid (PPS3-TT) and determined the antibody response and efficacy of vaccination against systemic and pulmonary challenge with serotype 3 pneumococcus in immunized and control mice. Our results showed that the isotype and predominant IgG subclass of the PPS3 response differed between immunodeficient mouse strains and between immunodeficient and Wt mice, with CB8-/- mice having the most robust response. Vaccination protected Wt, CB4-/-, and sIgM-/- mice from death resulting from both systemic and pulmonary challenge, whereas CB8-/- mice were protected only from systemic and not from pulmonary challenge. Passive vaccination with PPS3-TT-induced sera from Wt, CB4 -/-, CD8-/-, and sIgM-/- mice protected naïve Wt mice from death due to pulmonary challenge; however, CB8 -/- mice were not protected by sera from Wt or CB8-/- mice. Our findings suggest that PPS-based vaccines can be effective in the setting of CD4 T-cell deficiency but that CD8 T cells could be required for vaccine-mediated protection against pulmonary challenge with serotype 3 pneumococcus.

Original languageEnglish (US)
Pages (from-to)1643-1650
Number of pages8
JournalInfection and Immunity
Volume75
Issue number4
DOIs
StatePublished - Apr 2007

Fingerprint

Pneumococcal Vaccines
Streptococcus pneumoniae
Lung
Immunoglobulin M
Tetanus Toxoid
Vaccination
Vaccines
Polysaccharides
Serogroup
T-Lymphocytes
Serum
Inbred C57BL Mouse
Antibody Formation
Immunoglobulin G

ASJC Scopus subject areas

  • Immunology

Cite this

Pneumococcal capsular polysaccharide vaccine-mediated protection against serotype 3 Streptococcus pneumoniae in immunodeficient mice. / Tian, Haijun; Groner, Avi; Boes, Marianne; Pirofski, Liise-anne.

In: Infection and Immunity, Vol. 75, No. 4, 04.2007, p. 1643-1650.

Research output: Contribution to journalArticle

@article{79ec9e228dff4186be072f3d33a11685,
title = "Pneumococcal capsular polysaccharide vaccine-mediated protection against serotype 3 Streptococcus pneumoniae in immunodeficient mice",
abstract = "Pneumococcal capsular polysaccharide (PPS) vaccines are less immunogenic in immunocompromised than immunocompetent individuals. However, neither the efficacy of PPS vaccines in immunocompromised individuals nor the host cellular subsets required for vaccine efficacy against pneumococcal disease have been directly investigated. In this study, we vaccinated CD4-deicient (CD4 -/-), CD8-deficient (CB8-/-), and secretory immunoglobulin M-deficient (sIgM-/-) mice and wild-type C57BL/6 (Wt) mice with a conjugate of PPS of serotype 3 and tetanus toxoid (PPS3-TT) and determined the antibody response and efficacy of vaccination against systemic and pulmonary challenge with serotype 3 pneumococcus in immunized and control mice. Our results showed that the isotype and predominant IgG subclass of the PPS3 response differed between immunodeficient mouse strains and between immunodeficient and Wt mice, with CB8-/- mice having the most robust response. Vaccination protected Wt, CB4-/-, and sIgM-/- mice from death resulting from both systemic and pulmonary challenge, whereas CB8-/- mice were protected only from systemic and not from pulmonary challenge. Passive vaccination with PPS3-TT-induced sera from Wt, CB4 -/-, CD8-/-, and sIgM-/- mice protected na{\"i}ve Wt mice from death due to pulmonary challenge; however, CB8 -/- mice were not protected by sera from Wt or CB8-/- mice. Our findings suggest that PPS-based vaccines can be effective in the setting of CD4 T-cell deficiency but that CD8 T cells could be required for vaccine-mediated protection against pulmonary challenge with serotype 3 pneumococcus.",
author = "Haijun Tian and Avi Groner and Marianne Boes and Liise-anne Pirofski",
year = "2007",
month = "4",
doi = "10.1128/IAI.01371-06",
language = "English (US)",
volume = "75",
pages = "1643--1650",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "4",

}

TY - JOUR

T1 - Pneumococcal capsular polysaccharide vaccine-mediated protection against serotype 3 Streptococcus pneumoniae in immunodeficient mice

AU - Tian, Haijun

AU - Groner, Avi

AU - Boes, Marianne

AU - Pirofski, Liise-anne

PY - 2007/4

Y1 - 2007/4

N2 - Pneumococcal capsular polysaccharide (PPS) vaccines are less immunogenic in immunocompromised than immunocompetent individuals. However, neither the efficacy of PPS vaccines in immunocompromised individuals nor the host cellular subsets required for vaccine efficacy against pneumococcal disease have been directly investigated. In this study, we vaccinated CD4-deicient (CD4 -/-), CD8-deficient (CB8-/-), and secretory immunoglobulin M-deficient (sIgM-/-) mice and wild-type C57BL/6 (Wt) mice with a conjugate of PPS of serotype 3 and tetanus toxoid (PPS3-TT) and determined the antibody response and efficacy of vaccination against systemic and pulmonary challenge with serotype 3 pneumococcus in immunized and control mice. Our results showed that the isotype and predominant IgG subclass of the PPS3 response differed between immunodeficient mouse strains and between immunodeficient and Wt mice, with CB8-/- mice having the most robust response. Vaccination protected Wt, CB4-/-, and sIgM-/- mice from death resulting from both systemic and pulmonary challenge, whereas CB8-/- mice were protected only from systemic and not from pulmonary challenge. Passive vaccination with PPS3-TT-induced sera from Wt, CB4 -/-, CD8-/-, and sIgM-/- mice protected naïve Wt mice from death due to pulmonary challenge; however, CB8 -/- mice were not protected by sera from Wt or CB8-/- mice. Our findings suggest that PPS-based vaccines can be effective in the setting of CD4 T-cell deficiency but that CD8 T cells could be required for vaccine-mediated protection against pulmonary challenge with serotype 3 pneumococcus.

AB - Pneumococcal capsular polysaccharide (PPS) vaccines are less immunogenic in immunocompromised than immunocompetent individuals. However, neither the efficacy of PPS vaccines in immunocompromised individuals nor the host cellular subsets required for vaccine efficacy against pneumococcal disease have been directly investigated. In this study, we vaccinated CD4-deicient (CD4 -/-), CD8-deficient (CB8-/-), and secretory immunoglobulin M-deficient (sIgM-/-) mice and wild-type C57BL/6 (Wt) mice with a conjugate of PPS of serotype 3 and tetanus toxoid (PPS3-TT) and determined the antibody response and efficacy of vaccination against systemic and pulmonary challenge with serotype 3 pneumococcus in immunized and control mice. Our results showed that the isotype and predominant IgG subclass of the PPS3 response differed between immunodeficient mouse strains and between immunodeficient and Wt mice, with CB8-/- mice having the most robust response. Vaccination protected Wt, CB4-/-, and sIgM-/- mice from death resulting from both systemic and pulmonary challenge, whereas CB8-/- mice were protected only from systemic and not from pulmonary challenge. Passive vaccination with PPS3-TT-induced sera from Wt, CB4 -/-, CD8-/-, and sIgM-/- mice protected naïve Wt mice from death due to pulmonary challenge; however, CB8 -/- mice were not protected by sera from Wt or CB8-/- mice. Our findings suggest that PPS-based vaccines can be effective in the setting of CD4 T-cell deficiency but that CD8 T cells could be required for vaccine-mediated protection against pulmonary challenge with serotype 3 pneumococcus.

UR - http://www.scopus.com/inward/record.url?scp=34147178159&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34147178159&partnerID=8YFLogxK

U2 - 10.1128/IAI.01371-06

DO - 10.1128/IAI.01371-06

M3 - Article

VL - 75

SP - 1643

EP - 1650

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 4

ER -