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Infection and Immunity, April 2007, p. 1643-1650, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.01371-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Pneumococcal Capsular Polysaccharide Vaccine-Mediated Protection against Serotype 3 Streptococcus pneumoniae in Immunodeficient Mice

Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York 10461,¹ Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115,² Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461³

Received 25 August 2006/ Returned for modification 17 October 2006/ Accepted 3 January 2007

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-deficient (CD4^–/–), CD8-deficient (CD8^–/–), 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 CD8^–/– mice having the most robust response. Vaccination protected Wt, CD4^–/–, and sIgM^–/– mice from death resulting from both systemic and pulmonary challenge, whereas CD8^–/– mice were protected only from systemic and not from pulmonary challenge. Passive vaccination with PPS3-TT-induced sera from Wt, CD4^–/–, CD8^–/–, and sIgM^–/– mice protected naïve Wt mice from death due to pulmonary challenge; however, CD8^–/– mice were not protected by sera from Wt or CD8^–/– 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.

Published ahead of print on 12 January 2007.

Editor: J. N. Weiser