PMID- 27104338 OWN - NLM STAT- MEDLINE DCOM- 20171023 LR - 20181113 IS - 2164-554X (Electronic) IS - 2164-5515 (Print) IS - 2164-5515 (Linking) VI - 12 IP - 9 DP - 2016 Sep TI - Phosphate substitution in an AlOOH - TLR4 adjuvant system (SPA08) modulates the immunogenicity of Serovar E MOMP from Chlamydia trachomatis. PG - 2341-50 LID - 10.1080/21645515.2016.1168958 [doi] AB - 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. FAU - Visan, Lucian AU - Visan L AD - a Research & Non Clinical Safety Department , Sanofi Pasteur , Marcy l'Etoile , France. FAU - Sanchez, Violette AU - Sanchez V AD - a Research & Non Clinical Safety Department , Sanofi Pasteur , Marcy l'Etoile , France. FAU - Kania, Margaux AU - Kania M AD - b Bioprocess Research and Development, Sanofi Pasteur , Toronto , ON , Canada. FAU - de Montfort, Aymeric AU - de Montfort A AD - a Research & Non Clinical Safety Department , Sanofi Pasteur , Marcy l'Etoile , France. FAU - de la Maza, Luis M AU - de la Maza LM AD - c Department of Pathology and Laboratory Medicine , Medical Sciences I, University of California , Irvine , CA , USA. FAU - Ausar, Salvador Fernando AU - Ausar SF AD - b Bioprocess Research and Development, Sanofi Pasteur , Toronto , ON , Canada. LA - eng PT - Journal Article DEP - 20160422 PL - United States TA - Hum Vaccin Immunother JT - Human vaccines & immunotherapeutics JID - 101572652 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antibodies, Bacterial) RN - 0 (Antibodies, Neutralizing) RN - 0 (Bacterial Outer Membrane Proteins) RN - 0 (Bacterial Vaccines) RN - 0 (Immunoglobulin G) RN - 0 (Phosphates) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) RN - 0 (Vaccines, Subunit) RN - 0 (Vaccines, Synthetic) RN - 5QB0T2IUN0 (Aluminum Hydroxide) RN - 63957-70-0 (aluminum oxide hydroxide) RN - LMI26O6933 (Aluminum Oxide) SB - IM MH - Adjuvants, Immunologic/*administration & dosage MH - Aluminum Hydroxide/*administration & dosage MH - Aluminum Oxide/*administration & dosage MH - Animals MH - Antibodies, Bacterial/blood MH - Antibodies, Neutralizing/blood MH - Bacterial Outer Membrane Proteins/administration & dosage/genetics/*immunology MH - Bacterial Vaccines/administration & dosage/genetics/*immunology MH - Chlamydia trachomatis/*immunology MH - Female MH - Immunoglobulin G/blood MH - Mice MH - Phosphates/*administration & dosage MH - Toll-Like Receptor 4/*administration & dosage MH - Vaccines, Subunit/administration & dosage/genetics/immunology MH - Vaccines, Synthetic/administration & dosage/genetics/immunology PMC - PMC5027717 OTO - NOTNLM OT - Chlamydia trachomatis OT - IgG response OT - MOMP OT - T cell response OT - TLR4 agonist OT - aluminum hydroxide adjuvant OT - immunomodulation OT - phosphate substitution OT - vaccine EDAT- 2016/04/23 06:00 MHDA- 2017/10/24 06:00 PMCR- 2017/04/22 CRDT- 2016/04/23 06:00 PHST- 2016/04/23 06:00 [entrez] PHST- 2016/04/23 06:00 [pubmed] PHST- 2017/10/24 06:00 [medline] PHST- 2017/04/22 00:00 [pmc-release] AID - 1168958 [pii] AID - 10.1080/21645515.2016.1168958 [doi] PST - ppublish SO - Hum Vaccin Immunother. 2016 Sep;12(9):2341-50. doi: 10.1080/21645515.2016.1168958. Epub 2016 Apr 22.