Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis.
Chlamydia trachomatis is one of the most common sexually transmitted pathogens and the development of an effective vaccine is highly desirable. The Major Outer Membrane Protein (MOMP) is one of the most abundant and immunogenic chlamydial proteins. Here we investigated the effects of phosphate substitution on the physicochemical and immunochemical properties of an experimental vaccine composed of serovar E recombinant MOMP (rMOMP) and a proprietary adjuvant system SPA08, consisting of aluminum oxyhydroxide (AlOOH) containing the TLR4 agonist E6020. An increase in phosphate substitution in the AlOOH component of the adjuvant markedly decreased the adsorptive coefficient and adsorptive capacity for both Ser E rMOMP and E6020. In vaccine formulations used for immunizations, phosphate substitution induced a decrease in the % adsorption of Ser E rMOMP without affecting the % adsorption of E6020. Immunogenicity studies in CD1 mice showed that an increase in phosphate substitution of the SPA08 adjuvant resulted in an increase in Ser E rMOMP-specific serum total IgG and IgG1 but not IgG2a titers. The degree of phosphate substitution in SPA08 also significantly increased in vitro neutralization concomitant with a decrease in proinflammatory cytokines secreted by Ser E rMOMP-restimulated splenocytes. Taken together, the results of these studies suggest that the degree of phosphate substitution in AlOOH greatly affects the adsorption of E6020 and Ser E rMOMP to AlOOH resulting in significant effects on vaccine-induced cellular and humoral responses.
a Research & Non Clinical Safety Department , Sanofi Pasteur , Marcy l'Etoile , France.
Lucian
L
Visan
a Research & Non Clinical Safety Department , Sanofi Pasteur , Marcy l'Etoile , France.
Violette
V
Sanchez
b Bioprocess Research and Development, Sanofi Pasteur , Toronto , ON , Canada.
Margaux
M
Kania
a Research & Non Clinical Safety Department , Sanofi Pasteur , Marcy l'Etoile , France.
Aymeric
A
de Montfort
c Department of Pathology and Laboratory Medicine , Medical Sciences I, University of California , Irvine , CA , USA.
Luis M
LM
de la Maza
b Bioprocess Research and Development, Sanofi Pasteur , Toronto , ON , Canada.
Salvador Fernando
SF
Ausar
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000536:Aluminum Hydroxide / Q000008:administration & dosage*; D000537:Aluminum Oxide / Q000008:administration & dosage*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000097:blood; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000276:immunology*; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D010710:Phosphates / Q000008:administration & dosage*; D051197:Toll-Like Receptor 4 / Q000008:administration & dosage*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D010710:Phosphates; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D000536:Aluminum Hydroxide; C069471:aluminum oxide hydroxide; D000537:Aluminum Oxide
Chlamydia trachomatis; IgG response; MOMP; T cell response; TLR4 agonist; aluminum hydroxide adjuvant; immunomodulation; phosphate substitution; vaccine