TY - JOUR
T1 - Th17-mediated cross protection against pneumococcal carriage by vaccination with a variable antigen
AU - Kuipers, Kirsten
AU - Jong, Wouter S.P.
AU - van der Gaast-de Jongh, Christa E.
AU - Houben, Diane
AU - van Opzeeland, Fred
AU - Simonetti, Elles
AU - van Selm, Saskia
AU - de Groot, Ronald
AU - Koenders, Marije I.
AU - Azarian, Taj
AU - Pupo, Elder
AU - van der Ley, Peter
AU - Langereis, Jeroen D.
AU - Zomer, Aldert
AU - Luirink, Joen
AU - de Jonge, Marien I.
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Serotype-specific protection against Streptococcus pneumoniae is an important limitation of the current polysaccharide-based vaccines. To prevent serotype replacement, reduce transmission, and limit the emergence of new variants, it is essential to induce broad protection and restrict pneumococcal colonization. In this study, we used a prototype vaccine formulation consisting of lipopolysaccharide (LPS)-detoxified outer membrane vesicles (OMVs) from Salmonella enterica serovar Typhimurium displaying the variable N terminus of PspA (α1α2 ) for intranasal vaccination, which induced strong Th17 immunity associated with a substantial reduction of pneumococcal colonization. Despite the variable nature of this protein, a common major histocompatibility complex class (MHC-II) epitope was identified, based on in silico prediction combined with ex vivo screening, and was essential for interleukin-17 A (IL-17A)-mediated cross-reactivity and associated with cross protection. Based on 1,352 PspA sequences derived from a pneumococcal carriage cohort, this OMV-based vaccine formulation containing a single α1α2 type was estimated to cover 19.1% of strains, illustrating the potential of Th17-mediated cross protection.
AB - Serotype-specific protection against Streptococcus pneumoniae is an important limitation of the current polysaccharide-based vaccines. To prevent serotype replacement, reduce transmission, and limit the emergence of new variants, it is essential to induce broad protection and restrict pneumococcal colonization. In this study, we used a prototype vaccine formulation consisting of lipopolysaccharide (LPS)-detoxified outer membrane vesicles (OMVs) from Salmonella enterica serovar Typhimurium displaying the variable N terminus of PspA (α1α2 ) for intranasal vaccination, which induced strong Th17 immunity associated with a substantial reduction of pneumococcal colonization. Despite the variable nature of this protein, a common major histocompatibility complex class (MHC-II) epitope was identified, based on in silico prediction combined with ex vivo screening, and was essential for interleukin-17 A (IL-17A)-mediated cross-reactivity and associated with cross protection. Based on 1,352 PspA sequences derived from a pneumococcal carriage cohort, this OMV-based vaccine formulation containing a single α1α2 type was estimated to cover 19.1% of strains, illustrating the potential of Th17-mediated cross protection.
KW - Antigen surface display
KW - Autotransporter Hbp
KW - Broad protection
KW - Colonization
KW - Intranasal vaccination
KW - Protein antigens
KW - PspA
KW - Salmonella outer membrane vesicle (OMV)
KW - Streptococcus pneumoniae
KW - Th17
UR - http://www.scopus.com/inward/record.url?scp=85029737478&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85029737478&partnerID=8YFLogxK
U2 - 10.1128/IAI.00281-17
DO - 10.1128/IAI.00281-17
M3 - Article
C2 - 28717032
AN - SCOPUS:85029737478
SN - 0019-9567
VL - 85
JO - Infection and Immunity
JF - Infection and Immunity
IS - 10
M1 - e00281-17
ER -
