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S almonella T yphi O mp S 1 and O mp S 2 porins are potent protective immunogens with adjuvant properties
Author(s) -
MorenoEutimio Mario A.,
TenorioCalvo Alejandra,
PastelinPalacios Rodolfo,
PerezShibayama Christian,
GilCruz Cristina,
LópezSantiago Rubén,
Baeza Isabel,
FernándezMora Marcos,
Bonifaz Laura,
Isibasi Armando,
Calva Edmundo,
LópezMacías Constantino
Publication year - 2013
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12093
Subject(s) - antigen , immune system , microbiology and biotechnology , ovalbumin , chemistry , antibody , biology , immunology
Summary S almonella enterica serovar T yphi ( S . T yphi) is the causal agent of typhoid fever, a disease that primarily affects developing countries. Various antigens from this bacterium have been reported to be targets of the immune response. Recently, the S . T yphi genome has been shown to encode two porins – O mp S 1 and O mp S 2 – which are expressed at low levels under in vitro culture conditions. In this study, we demonstrate that immunizing mice with either O mp S 1 or O mp S 2 induced production of specific, long‐term antibody titres and conferred protection against S . T yphi challenge; in particular, O mp S 1 was more immunogenic and conferred greater protective effects than O mp S 2. We also found that O mp S 1 is a T oll‐like receptor 4 ( TLR 4) agonist, whereas O mp S 2 is a TLR 2 and TLR 4 agonist. Both porins induced the production of tumour necrosis factor and interleukin‐6, and O mp S 2 was also able to induce interleukin‐10 production. Furthermore, O mp S 1 induced the over‐expression of MHC II molecules in dendritic cells and O mp S 2 induced the over‐expression of CD 40 molecules in macrophages and dendritic cells. Co‐immunization of O mp S 1 or O mp S 2 with ovalbumin ( OVA ) increased anti‐ OVA antibody titres, the duration and isotype diversity of the OVA ‐specific antibody response, and the proliferation of T lymphocytes. These porins also had adjuvant effects on the antibody response when co‐immunized with either the V i capsular antigen from S . T yphi or inactivated 2009 pandemic influenza A ( H 1 N 1) virus [ A ( H 1 N 1)pdm09]. Taken together, the data indicate that O mp S 1 and O mp S 2, despite being expressed at low levels under in vitro culture conditions, are potent protective immunogens with intrinsic adjuvant properties.