SalmonellaTyphi Porins OmpC and OmpF Are Potent Adjuvants for T-Dependent and T-Independent Antigens.
Several microbial components, such as bacterial DNA and flagellin, have been used as experimental vaccine adjuvants because of their inherent capacity to efficiently activate innate immune responses. Likewise, our previous work has shown that the majorSalmonellaTyphi (S. Typhi) outer membrane proteins OmpC and OmpF (porins) are highly immunogenic protective antigens that efficiently stimulate innate and adaptive immune responses in the absence of exogenous adjuvants. Moreover,S. Typhi porins induce the expression of costimulatory molecules on antigen-presenting cells through toll-like receptor canonical signaling pathways. However, the potential of majorS. Typhi porins to be used as vaccine adjuvants remains unknown. Here, we evaluated the adjuvant properties ofS. Typhi porins against a range of experimental and clinically relevant antigens. Co-immunization ofS. Typhi porins with ovalbumin (OVA), an otherwise poorly immunogenic antigen, enhanced anti-OVA IgG titers, antibody class switching, and affinity maturation. This adjuvant effect was dependent on CD4+T-cell cooperation and was associated with an increase in IFN-γ, IL-17A, and IL-2 production by OVA-specific CD4+T cells. Furthermore, co-immunization ofS. Typhi porins with an inactivated H1N1 2009 pandemic influenza virus experimental vaccine elicited higher hemagglutinating anti-influenza IgG titers, antibody class switching, and affinity maturation. Unexpectedly, co-administration ofS. Typhi porins with purified, unconjugated Vi capsular polysaccharide vaccine (Vi CPS)-a T-independent antigen-induced higher IgG antibody titers and class switching. Together, our results suggest thatS. Typhi porins OmpC and OmpF are versatile vaccine adjuvants, which could be used to enhance T-cell immune responses toward a Th1/Th17 profile, while improving antibody responses to otherwise poorly immunogenic T-dependent and T-independent antigens.
Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre "Siglo XXI", Mexican Social Security Institute, Mexico City, Mexico; Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.
Marisol
M
Pérez-Toledo
Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre "Siglo XXI", Mexican Social Security Institute, Mexico City, Mexico; Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.
Nuriban
N
Valero-Pacheco
Facultad de Química, Universidad Nacional Autónoma de México , Mexico City , Mexico.
Rodolfo
R
Pastelin-Palacios
Institute of Immunobiology, Kantonsspital St. Gallen , St. Gallen , Switzerland.
Cristina
C
Gil-Cruz
Institute of Immunobiology, Kantonsspital St. Gallen , St. Gallen , Switzerland.
Christian
C
Perez-Shibayama
Immunity and Inflammation Research Unit, Hospital Juárez de México, Ministry of Health , Mexico City , Mexico.
Mario A
MA
Moreno-Eutimio
Facultad de Medicina, Departamento de Medicina Experimental, Universidad Nacional Autónoma de México , Mexico City , Mexico.
Ingeborg
I
Becker
Unit of R&D in Bioprocesses (UDIBI), Department of Immunology, National School of Biological Sciences, National Polytechnic Institute , Mexico City , Mexico.
Sonia Mayra
SM
Pérez-Tapia
Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre "Siglo XXI", Mexican Social Security Institute , Mexico City , Mexico.
Lourdes
L
Arriaga-Pizano
MRC Centre for Immune Regulation, College of Medical and Dental Sciences, Institute of Immunology and Immunotherapy, University of Birmingham , Birmingham , UK.
Adam F
AF
Cunningham
Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre "Siglo XXI", Mexican Social Security Institute , Mexico City , Mexico.
Armando
A
Isibasi
Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre "Siglo XXI", Mexican Social Security Institute , Mexico City , Mexico.
Laura C
LC
Bonifaz
Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre "Siglo XXI", Mexican Social Security Institute, Mexico City, Mexico; Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Constantino
C
López-Macías
IFN-gamma; IL-17; Vi polysaccharide; adjuvants; antibody responses; influenza; porins