Conjugate vaccines (capsular polysaccharides conjugated to carrier proteins) against Streptococcus pneumoniae are available but are limited by the serotypes included in the vaccines;furthermore serotype replacement had been observed in many countries that have introduced conjugate vaccines. Therefore, alternative vaccines that provide species-specific protection would represent an important public health advance. Two types of acquired immunity, TH17 cells- and antibody-mediated, have been shown to provide protection against nasopharyngeal colonization and invasive disease, respectively. Proteins on the bacterial surface represent attractive targets for vaccine development due to their accessibility to antibodies and the possibility of promoting opsonophagocytosis. We will develop a pneumococcal species-conserved surface protein library and screen it for vaccine candidates that provide TH17 dependent protection against colonization and antibody-mediated protection against pneumococcal disease. Screens for TH17 stimulatory proteins will be carried out first in mouse models for elicitation of IL-17A after pneumococcal exposure;these results will then be confirmed by examination of the TH17 response from adenoidal cells obtained from children. Antigens that elicit these responses in both mice and pediatric adenoidal cells will then be tested for protection against colonization and disease in murine models. Successful completion of this will both advance the field of pneumococcal vaccine research and provide a proof-of-concept strategy for antigen discovery for other pathogens, such as Staphylococcus aureus and group A streptococcus, in which both T and B cell immunity play important and complementary roles.

Public Health Relevance

The proposed research is highly relevant to public health because Streptococcus pneumoniae is an important cause of childhood disease in the US and throughout the world. We will screen murine and pediatric mucosal lymphoid cells to identify protective antigens from a library of conserved, likely surface-exposed pneumococcal proteins. The results of our investigations will advance the development of a novel pneumococcal vaccine in children.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI103480-02
Application #
8722429
Study Section
Vaccines Against Microbial Diseases (VMD)
Program Officer
Taylor, Christopher E,
Project Start
2013-08-16
Project End
2015-07-31
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
2
Fiscal Year
2014
Total Cost
$194,354
Indirect Cost
$66,354
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
Hua, Chun-Zhen; Howard, Angela; Malley, Richard et al. (2014) Effect of nonheme iron-containing ferritin Dpr in the stress response and virulence of pneumococci. Infect Immun 82:3939-47